Via Medical News Today, a great example of the degree to which researchers are unravelling the biochemical mechanisms of Alzheimer's disease (AD): "Oxidative damage has long been suspected as playing an early critical role in AD. Because the events that trigger the beginnings of AD are still unknown, [researchers] began targeting research on the reaction between the [amyloid beta] plaque and immune cells. ... researchers found that the microglia had the appropriate immune response that the plaque was harmful, but then the protein Vav was found to be a component in oxidative damage since elimination of the protein resulted in reduced free radical production. ... by understanding this biological component in the disease process, it holds the potential to 'push back the severity of the disease.'" Other groups have shown that even excessive amyloid can be prevented from causing neurodegeneration - perhaps there's an effective therapy to be made from breaking the chain from amyloid to oxidative stress to neural cell death.
This press release from Yahoo! News notes an ongoing research program aimed at the rapid tissue engineering of whole kidneys from a patient's own cells: "Using principles of 'tissue self-assembly' (cells coming together to form actual tissues such as a kidney, heart, lung etc.) and stem cell research, scientists involved with the MUSC Bioengineered Kidney Project are testing the possibility of creating a new kidney from a patient's cells. ... While other researchers are trying to grow kidney tissues slowly, the essence of [this technological approach] is rapid directed tissue self-assembly, which is based on exploration of the tissue fusion phenomenon." This program has been running for a while - we'll see what comes of it. Reading between the lines, this release something of a positioning piece for funding; nothing wrong with that, and it is helpful to see intent and goals as they are expressed in the field, but don't mistake it for actual results.
Is it really right that you know more about the workings of your car than your body? You can always buy another car if you fail to take good care of the one you have. If you want to live a longer, healthier life, however, it is a very good idea to become more educated about what is actually going on inside that aging body of yours. A great deal more is known about the biochemistry of aging than present day medical technologies allow us to manipulate safely, but this state of affairs is changing rapidly. Getting yourself up to speed is the first step towards deciding how you should help to shape your future health and longevity.
With that in mind, here's a little about the mitochondrial-lysosomal axis theory of aging and its relationship to your aging process. Like much of modern biochemistry, a summary of the science is actually nowhere near as complex as the name makes it sound. The following paper describes a relationship between cellular processes, damage and failure modes that take place in the mitochondria and the lysosomes, components within the cell known as organelles.
Aging (senescence) is characterized by a progressive accumulation of macromolecular damage, supposedly due to a continuous minor oxidative stress associated with mitochondrial respiration. Aging mainly affects long-lived postmitotic cells, such as neurons and cardiac myocytes, which neither divide and dilute damaged structures, nor are replaced by newly differentiated cells. Because of inherent imperfect lysosomal degradation (autophagy) and other self-repair mechanisms, damaged structures (biological "garbage") progressively accumulate within such cells, both extra- and intralysosomally. Defective mitochondria and aggregated proteins are the most typical forms of extralysosomal "garbage", while [lipofuscin] represents intralysosomal "garbage".
Based on findings that autophagy is diminished in lipofuscin-loaded cells and that cellular lipofuscin content positively correlates with oxidative stress and mitochondrial damage, we have proposed the mitochondrial-lysosomal axis theory of aging, according to which mitochondrial turnover progressively declines with age, resulting in decreased ATP production and increased oxidative damage.
The inherited Batten disease shows what happens when lipofuscin buildup truly runs amok - a very early death. As the above paper shows, scientists are building an ever greater understanding of exactly how it is that our cells run down with age. Some groups - such as those funded by donations to the Methuselah Foundation, or those aiming at specific age-related conditions resulting from this damage - are working towards fixing these problems.
If we want to see more rapid progress towards therapies capable of repairing this sort of age-related cellular damage, more funding and more researchers are needed in these areas. This is something that you can help to bring about; so take a moment to think about your priorities!
For those keeping tabs on stem cell politics - and they way it dominates and twists mainstream reporting of actual science and progress - TIME provides something of an overview: "Not all embryonic-stem-cell lines are created equal. Some are more readily driven down a certain lineage, such as heart cells, while others more easily become nerve. We don't understand how it happens, but it does mean we need diversity. ... researchers announced this summer that they would develop new cell lines through somatic cell nuclear transfer, or therapeutic cloning. ... these cells would match the patient's dna, so the body would be less likely to reject a transplant derived from them. Even more exciting for researchers, however, is that this technique can yield embryos that serve as the perfect disease in a dish, revealing how a disease unfolds from the very first hours." For politics and funding, the article is another biased viewpoint in a world full of biased viewpoints. The field is complex, comparatively well-funded and moving rapidly - but the technical goals are challenging enough without adding meddling politicians to the list.
A great deal of clever engineering is taking place in the development of new methods of targeting, delivering and activating pinpoint anti-cancer therapies. This technology will have utility in the future - the ability to target very small areas or very specific types of cell in the body opens up all sorts of possibilities throughout medicine. Here is an example via Israel21c: "The two big problems with photodynamic therapy are getting the light-sensitive drug to only target cancer cells, and delivering light to the drug to activate it once it is in the right place. We've uniquely combined two cutting-edge technologies to direct a drug to cancer cells and to generate a light source inside the cells. This stops the drug killing healthy cells ... we've shown in the research that if you take a cell culture and treat it with the light sensitive compound called luminol - it produces chemiluminescence in the cell which activates the light sensitive molecules and kills the cells. ... We're now in the pre-clinical stage using models of leukemia, but we're not limited to that cancer."
Rejuvenation Research Volume 9 Number 3 is out and available online, in case you hadn't noticed. While, as usual, more than I note is there for your perusal, the following items caught my eye:
Given the constitutive expression of telomerase in the majority of human tumors, telomerase inhibition is an attractive, broad-spectrum therapeutic target for cancer treatment. Therapeutic strategies for inhibiting telomerase activity have included both targeting components of telomerase (the protein component, TERT, or the RNA component, TERC) or by directly targeting telomere DNA structures. Recently a combination telomerase inhibition therapy has been studied also. ... The 10% to 15% of immortalized cancer cells that do not express telomerase use a recombination based mechanism for maintaining telomere structures that has been called the alternative lengthening of telomeres (ALT). In view of the increasing study of telomerase inhibitors as anticancer treatments, it will be crucial to determine whether inhibition of telomerase will select for cancer cells that activate ALT mechanisms of telomere maintenance.
It seems clear that much can be done with a better understanding of the cellular mechanisms hijacked and redirected by cancer. Cancer is, in essence and skipping over most of the important subtleties, a failure of the body's turnover mechanism for cells - it is suddenly immortal cells run amok. At the more ambitious end of the pool, we have proposals like Aubrey de Grey's Whole-body Interdiction of Lengthening of Telomeres, a part of the Strategies for Engineered Negligible Senescence (SENS). Considering near term goals, however, a number of research groups and young companies are hacking away at the undergrowth to find the best gains to be made in the short term.
Reduction of oxidative stress within mitochondria is a major focus and important part in the SENS agenda. The age-related accumulation of mitochondria rich in oxidatively altered DNA may be a biomarker of malfunctioning and increased oxidative stress. Macroautophagy is the cell repair mechanism responsible for the disposal of excess or altered mitochondria under the inhibitory control of nutrition and insulin, and may mediate the antiaging effects of caloric restriction. ... It is concluded that the age-related changes in [mitochondrial DNA (mtDNA)] and function are likely to be the consequence of a failure of macroautophagy in the recognition and disposal of a small number of severely injured mitochondria, and that easy and safe ways are available to counteract this change.
I am very pleased to see more researchers taking SENS as a challenge, or goal list. This sort of mindset will go a long way towards bringing people on board and putting accomplishments on the table. More to the point, and like the protofection folk, this group is demonstrating some tangible results - albeit not so far advanced and not in vivo.
Werner syndrome (WS) is a premature aging disorder that is widely used as a model for some aspects of the normal human aging process. Individuals with WS have several of the characteristics of normal aging, such as cataracts, hair graying, and skin aging, but manifest these at an early age. In addition, WS is associated with high levels of inflammatory diseases such as atherosclerosis and type II diabetes. Recent data have indicated that fibroblasts derived from individuals with WS have activated a major molecular pathway involved in inflammation. This observation ties in with the presence of high plasma levels of inflammatory cytokines in individuals with WS. In this paper, the authors discuss the possibility that WS is an example of "inflamm-aging," in that many of the phenotypic manifestations may result from an increased inflammatory state. Moreover, drugs that specifically block this inflammation pathway may be possible candidates for therapeutic intervention in WS.
Inflammaging is a great term - very catchy, to the point and representative of exactly what it is that chronic inflammation does to you. We need more of these catchy terms as we go forward in our attempts to bring an understanding of healthy life extension to a wider audience (starting with a replacement for "healthy life extension" and "anti-aging").
But back to the research at hand. This caught my eye precisely because scientists have recently nailed down progeria - another accelerated aging condition - to be the result of a biochemical process seen in "normal" aging that is exaggerated out of all proportion due to a single genetic mutation. The aging process is very multifaceted for most of us, but progeria is a case of one - apparently comparatively minor - facet racing ahead of all others to dominate and shorten life span.
Present indications are that Werner syndrome is a matter of failing DNA repair mechanisms; thus its syndromes are a consequence of an increased rate at which unrepaired DNA damage accumulates. That isn't completely cut and dried, however; it will be interesting to see how inflammation fits into this. What is the cause and what is the consequence? Further research will show the answer, and the knowledge gained will most likely benefit wider longevity research - just as for progeria.
Do people believe that they can make a difference, that they can help to change the world? Judging by these statistics from the Giving USA Foundation, the answer has to be yes:
The growth of nonprofit infrastructure, activism and advocacy in support of cancer, diabetes and Alzheimer's research demonstrates that a large fraction of the population are very willing to change the world so as to eliminate specific, well-understood causes of age-related suffering. Decades of messaging have gone into making the present public understanding of cancer as a disease with a cure, for example, or Alzheimer's as something other than a "normal part of aging." After a certain point, the message started by advocates becomes self-sustaining in the wider cultural conversation.
Including the roots of age-related degeneration in this category is a matter of education - and a matter of keeping at it. Persuading people that no degeneration, frailty or death should be a "normal part of aging" is a matter of delivering the message - ever-louder, ever more clearly, with ever greater professional support - and growing the community of healthy life extension supporters.
This isn't a novel or complex job; it's just hard work, and a repetition of long-proven methods. Look back to see how AIDS activists succeeded, or how cancer research advocacy grew in the 60s and 70s, or how present day Alzheimer's research supporters work. Real progress has been made in the past few years, but it's up to us to ensure this progress continues.
Each individual chooses whether to help bring about a future of longer, healthier lives - but it's our fault if most people never understand the potential of present day science, or that the choice to effectively attack degenerative aging presently exists. It you want something done, if you want people to help out and see matters your way, then you have to set the ball rolling yourself. There is no other way.
Via USA Today: "overweight and obese women spend an average of three more years in ill health than normal-weight women. Heavy men, on average, are sicker one more year than their thinner counterparts. Heavy people are more likely to suffer from pain, arthritis, type 2 diabetes, heart disease and other illnesses that may affect their ability to perform daily tasks ... An obese 30-year-old has as many chronic conditions as a normal-weight 50-year-old and reports quality of life that is worse than a 50-year-old." Correlation is not causation; a condition that prevents exercise can lead to weight gain if diet remains unchanged, for example. A look at what scientists understand about fat, inflammation and the roots of age-related disease should be a wake-up call, however. You have a great deal of control over the future trajectory of your health and its costs: make use of it.
The New York Times compares the present day with a past of shorter life spans and even more widespread suffering from age-related disease. "Diseases early in life left people predisposed to chronic illnesses when they grew older. ... Suppose you were a survivor of typhoid or tuberculosis. What would that do to aging? ... the number of chronic illnesses at age 50 was much higher in that group. ... Something is being undermined. Even the cancer rates were higher. Ye gods. We never would have suspected that. ... Men who had respiratory infections or measles tended to develop chronic lung disease decades later. Malaria often led to arthritis. Men who survived rheumatic fever later developed diseased heart valves." The reliability theory of aging and longevity goes a long way towards explaining why prevalence of chronic disease is linked to shorter life spans via an increased rate of cellular damage.
By way of a reminder, the 3rd International Conference on Healthy Ageing & Longevity kicks off on October 13th in Melbourne, Australia. Early registration continues through to August 31st; give it some thought, as the past two conferences were worthwhile affairs. The conference series is a good example of wealthy individuals stepping up to make a difference.
The Weller family of Australia are committed to organising the annual International Conferences on Healthy Ageing and Longevity for the next ten years, with the aim to promote interdisciplinary collaboration amongst the world's leading doctors, scientists, complementary healthcare professionals and policy makers in the field of health and ageing. The family has no connection with any company or product in the healthcare industry.
Held at the Scottsdale Marriott in Scottsdale, Arizona, the Alcor Life Extension Foundation's 6th Conference from October 6-8, 2006, will explore anti-aging research, life extension, nanomedicine and nanotechnology, whole body cryopreservation, cryonic revival and more.
Don't miss this opportunity to hear the most up-to-date information about the cryonics experiment being conducted at the Alcor Foundation, as well as possibilities of other life-extending sciences.
This year the theme of the conference will be Emerging Technologies of Human Enhancement. We'll be looking at recent and ongoing technological developments and discussing associated ethical and philosophical questions.
Dr. de Grey joins us to overview the [Strategies for Engineered Negligible Senescence (SENS)] plan and highlight how his proposed aging interventions closely parallel the molecular and cellular repairs that will be required to revive a well-vitrified cryonics patient.
Some common sense on taking care of your health in the here and now from Forbes: "People who get regular exercise, eat healthfully and avoid tobacco have a lower risk of chronic diseases that lead to premature death, such as heart disease, high blood pressure, diabetes and certain cancers. They also have reduced rates of disability, better mental health and cognitive function, and lower health costs. Conversely, individuals who are physically inactive are almost twice as likely to develop heart disease as active people, according to the report. Inactivity is also linked to the development of diabetes and colon cancer, and can result in loss of muscle strength and mass, which can lead to frailty and lethal falls. Yet, approximately one-third of persons age 65 or older have not engaged in any leisure-time physical activity within the past month." We are living through a revolution in medicine and biotechnology - why risk missing out on the healthy life extension medicine of the near future by damaging yourself to an early death?
The Calorie Restriction (CR) Society is raising funds for a new biomarker study: "how can you know whether your limited-calorie lifestyle really slows aging? And whether are not you are practicing calorie restriction, how will you know if supplements, exercise, amount of protein intake, hormone replacements or any other of the myriad choices that are persuasively argued for - actually accelerates aging or increases risk of cancer or other serious disease? An objective method of evaluation is vital to avoid life-shortening mistakes. That's why the Calorie Restriction Society has initiated a milestone study that will correlate human calorie restrictors' genetic expression and cell signaling indicators to clinical markers. Once these correlations are established, serious longevists will be equipped with easy-to-run clinical tests that indicate how well their regimens are working." The Society is looking for $230,000 in donations; matching grants will be posted soon.
If you found recent news on electrically engineered bone marrow interesting, then this piece from UPI is also good news: "damage to epithelial tissue such as skin results in strong, directional ion flow and generates an internal electrical field. Such fields are thought to guide moving cells by a process known as electrotaxis, in order to heal the wound. ... wounds may close faster or be driven open, depending on the direction of externally applied electrical signals similar in strength to those occurring naturally. The researchers also identified the genes that control electrotaxis as PI(3)Kgamma and PTEN, and propose electrical signals may be used in the future to direct cell growth during wound healing in cell and tissue engineering." Present day technology for manipulating electric fields on small scales is advanced, low-cost and reliable. This bodes well for the future of of this sort of research in tissue engineering - experimentation will be cheap, so progress will be rapid.
As scientists learn more of the biochemical mechanisms of memory, the first old-school drug pipeline products to treat the results of age-related cellular damage on these mechanisms are turning up at the door. Researchers "showed that ampakine drugs continue to reverse the effects of aging on a brain mechanism thought to underlie learning and memory even after they are no longer in the body. ... in the ampakine-treated rats, there was a significant increase in the production of brain-derived neurotrophic factor (BDNF), a protein known to play a key role in memory formation. They also found an increase in long-term potentiation (LTP), the process by which the connection between the brain cells is enhanced and memory is encoded. This enhancement is responsible for long-term cognitive function, higher learning and the ability to reason. With age, deficits in LTP emerge, and learning and memory loss occurs." This is very early stage research, needless to say.
Knowledge is everything; it allows you to take the technologies of yesterday and use them in new and far more powerful ways. The movement of a single brick could change the course of history - if you just knew where, when and how to place it.
Here is a good example of the power of placement:
An atherosclerosis plaque results when a buildup of cholesterol, inflammatory cells and fibrous tissue forms inside an artery. If a plaque ruptures, it can block blood flow to the heart or brain, causing heart attack or stroke.
While growing, plaques require an influx of nutrients, fats and cells, so they develop their own blood supply -- minute blood vessels that grow within the wall of arteries and penetrate the plaque. Many believe that cutting off this blood supply could stabilize or reduce plaques. In previous studies, fumagillin has been shown to be an effective agent for stopping the process that creates new blood vessels.
Riding on the nanoparticles, fumagillin is carried to the site of new blood vessel formation and stays there thanks to a fellow nanoparticle passenger -- a component that fastens the nanoparticles to cells found in newly developing blood vessels. Stuck in this position, the nanoparticle drops its load of fumagillin, concentrating it at the site of the atherosclerotic plaque.
In this study, the single dosage of fumagillin each rabbit received was 50,000 times lower than the total fumagillin dose used in an earlier experiment by another research group and yet reduced the growth of new blood vessels in plaques by 60 to 80 percent.
Researchers involved in first generation nanomedicine - equal parts nanoscale manufacture, biotechnology and ingenuity, mixed and then applied to medicine - are turning out impressive technology demonstrations of this nature at a rapid pace. Simple, abandoned drugs of the past become effective agents when precisely targeted to individual cells and microscopic locations in the body.
In essence, much of modern biotechnology is knowledge, positioning and targeting. With the enabling technologies of targeted delivery in hand, making changes doesn't require any further component much more complex than a brick. All the complexity is elsewhere: in manufacturing intricate nanoparticles; in the vast bioinformatics infrastructure; in our growing organized knowledge of biochemical mechanisms.
In the old school of drug discovery and development, it was all about the brick. Nowadays, the brick is almost the last thought in the process of developing new therapies - and we'll be the better for it.
Better biotechnology improves the quality of the old-school drug pipeline, as illustrated by this BBC article on a Alzheimer's drug: "Tests in mice have shown the drug, PBT2, prevents build up of the amyloid protein linked to the disease. Protein levels dropped by 60% within 24 hours of a single dose, and memory performance improved within five days. ... Human tests are due to start next month, followed by a major international trial next year. ... This data is compelling and very exciting because it shows that PBT2 not only may facilitate the clearance of [amyloid-beta] from the brain or prevent its production, but more importantly may improve cognition. ... Scientists still have a lot of work to do before a drug could be available for patients. Much more research is needed even to see whether preventing the amyloid build-up is really a true benefit for patients."
A minor roundup of odds and ends for you folk today:
Why do living things age? What genes influence longevity? Is it possible to extend youthfulness by means of genetic manipulation? What does the aging of a yeast cell have in common with the aging of a human being or a mouse? Dr. Guarente analyzes these tantalizing questions and others in this episode.
Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Despite scepticism concerning its bioavailability, a growing body of in vivo evidence indicates that resveratrol has protective effects in rodent models of stress and disease. Here, we provide a comprehensive and critical review of the in vivo data on resveratrol, and consider its potential as a therapeutic for humans.
As I've mentioned before, it's good to see the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging appearing on research papers; the backers are a positive force for change, acceleration and better results in mainstream aging research. As to the paper itself, I'll admit to being a resveratrol skeptic. I'm skeptical in general on whether this sort of direction - metabolic research, supplements, pills, and so forth - is one in which we should be focusing all our attention and resources. If the end goal is the defeat of aging, as opposed to developing some modestly successful therapies for specific age-related diseases, then we need to do much better than this. The bottom line: if you have a much more efficient mechanism, generating unrepaired cellular damage at a lower rate, you will still age, suffer and die. If you are treated with a modestly successful therapy for your age-related disease, you will still age, suffer and die.
Some things to ask yourself about any new supplement backed up by good laboratory work:
- Do the pills deliver the same potency and compound used in the laboratory?
- Will your body break it down before it does anything?
- Has the pill form been demonstrated to have the same (or any) beneficial effects in scientific studies?
- Is spending time, effort and money on this as effective for your future healthy and longevity as putting the same resources towards serious anti-aging research?
In all fairness, that last question is a tough one - but it is something you should think about. I think that we would all benefit from less time spent on pills and more time spent on advanced medicine: telomeres, stem cells, cancer therapies, mitochondria and real anti-aging medicine.
Identical twins who grow up together share just about everything, including their genes. But sometimes only one twin will have health problems when genetics predicts both of them should.
The advantage of studying twins is that they start out with the exact same genetic information. Therefore, differences in gene expression are attributable to different environmental factors rather than genetics. Such factors could cause a random genetic mutation or affects how DNA is packaged.
"There's a lot of variability in the severity of the disease, symptoms, and the response a patient will have to treatment. Differences in the expression of genes caused by environmental factors that modify DNA have a lot to do with this variability."
Reminders that age-related degeneration is a stochastic process of accumulating damage and resultant failure modes are all around us. We age and fail just like complex machines because we are complex machines.
The rate and type of cellular damage you accumulate over the years will be significantly different from your peers - even your genetically similar peers. All of us would benefit from the development of medical technologies capable of preventing or repairing this damage, however. Even incremental advances along this path will bring benefits to all, but this direction of research is quite different from that aimed at improving metabolic efficiency or reducing the rate at which damage occurs. Repairing cellular damage means the direct path to reversing aging, rather than the present focus on slowing it.
Technorati tags: life extension
Discover gives a brief introduction to cancer immunity in mice: "Cui bred the mouse and found that 40 percent of its offspring share a remarkable resistance to many forms of cancer. When the animals' immune systems identify a cancer cell, a genetic tweak allows their bodies to launch a massive attack of white blood cells that kills the budding tumor. ... When they inject white blood cells from any of these anticancer mice into their nonresistant brethren, the injected animals become resistant as well, fighting off induced cancer in a matter of weeks or avoiding it entirely. ... Cui has sampled a group of human volunteers and found that 10 to 15 percent have similar super cancer-fighting white blood cells. That could explain why some people never get cancer and why others' tumors spontaneously regress. Cui proposes injecting these people's white blood cells into cancer patients to see if he can transfer their immunity."
I received a professionally produced conference brochure from Alcor just today; their 6th conference later this year looks to be a very worthwhile event, headlined by an impressive cast of luminaries. This year's topic is "An Inside Look at the Science and Medicine of Tomorrow." From the Alcor website: "Is it possible to live to 1000 years of age or beyond? Will nanomedicine and medical nanorobots dramatically extend the human lifespan? Can cryopreserved organs and human beings be revived in the future? Join us and members of our community to hear distinguished speakers present their provocative insights into where we are today and what's possible tomorrow in antiaging, life extension research, nanotechnology, organ preservation, cryonics and more." Arizona is looking more and more like the place to be these days.
Within each and every one of your trillions of cells sits a molecular hour-glass. The time when each and every cell must stop dividing comes closer with every grain of sand that drops through this tiny clock.
The grains are letters of DNA code that fall off these cellular timepieces. Scientists call them telomeres and there is good evidence that they go wrong in cancer so that, by fixing them, tumours could be made to expire on schedule. Earlier this month, a team in California managed to inhibit the spread of melanoma skin cancer by exploiting this mechanism.
Longer life for your cells is not necessarily a good thing - cancer cells are an immortal machinery run amok, for example; an ultimately fatal hazard to finely tuned biochemistry that depends on cellular turnover and lifecycles. The melanoma research mentioned above is worth further reading if you are interested in seeing a facet of telomere research in action:
In the study, researchers found through gene expression profiling in mice that eight genes involved in glucose metabolism were lowered when telomerase was suppressed in skin cancer cells. The result was a return of pigmentation, frequently absent in advanced melanomas, and of cancer cells losing their metastatic potential.
"We introduced a telomerase inhibitor into melanoma cells and found that by suppressing telomerase, melanoma cells start to change," said Kashani-Sabet. "In some melanomas, pigmentation is lost. We found that when we are able to shut down telomerase, the cells regain functions previously lost, such as the ability to make pigment."
"As the cells become too acidic from the buildup of lactic acid, the proteins that control pigment production can be turned off, suggesting that glucose metabolism plays a key role when combined with telomerase in metastasis."
Shutting down metastasis is a very big deal in cancer treatment. A range of other telomere-related strategies are presently under exploration for the prevention or treatment of cancer. Unlike past generations of research, these are carefully tailored approaches based upon ever more accurate knowledge of the biochemical mechanisms at the root of cancer.
But what of telomeres and aging? From the Telegraph article:
Others believe that telomeres may hold the key to ageing itself. A team at Brown University in Rhode Island recently reported that cells with faulty telomeres made up about four per cent of connective tissue in five-year-old baboons. But in 30-year-olds, that number rose as high as 20 per cent, providing evidence to support the theory that old cells help make old bodies.
When telomeres run out, cells become "senescent". Under a microscope, they look bloated. Analyse the way that they use genes and one can see changes that make the senescent cells secrete factors that make tissues deteriorate. Because they hang around for years, rather than do something helpful like die, these old cells may well underpin age-related disease.
Perhaps a way to turn back telomeres can be found, marking the culmination of the search for the elixir of youth, although there is still a great deal of argument about whether it is ageing that shortens telomeres or whether stubby telomeres cause ageing.
The argument will be solved by further research - there are convincing positions on both sides, for all the original form of the telomere theory of aging has been largely abandoned. It seems clear that aging has many more contributory causes, and it is far from decided as to where shortened telomeres fit into the picture - other than as a cause of cancer, that is, where the science is as definitive as it gets in an very active field.
Amongst the research groups who see therapies for the root causes of degenerative aging emerging from telomere science are young companies like Phoenix Biomolecular, Sierra Sciences and Telomolecular. You should take a look at what they have to say about their areas of research.
The MIT Technology Review is running an interview with researcher Thomas Perls on his centenarian study and the forthcoming Long Life Family Study: "Not only do these people live long, but many of them seem to escape the disability associated with diseases of aging or to compress that disability period into a short time span very late in life. ... I think genes that modulate risk for heart disease will be very important. That's still the number-one killer, even among the very old. In addition, more and more scientific studies show that fat metabolism will play a big role. ... We previously found that centenarians were more likely to have a certain variant of the gene for microsomal transfer protein, which plays a role in packaging cholesterol. However, subsequent studies have had different results. ... That shows how important it is to confirm results in different populations and suggests that the importance of various genetic longevity factors varies from one population to another."
Researchers are methodically chipping away at the mysteries of cellular differentiation; the more they understand, the more they can do to realize the dream of true regenerative medicine. Via EurekAlert!: scientists "have transformed adult stem cells taken from human adipose - or fat tissue - into smooth muscle cells, which help the normal function of a multitude of organs like the intestine, bladder and arteries. ... Fat tissue may prove a reliable source of smooth muscle cells that we can use to regenerate and repair damaged organs ... Smooth muscle cells have also been produced from stem cells found in the brain and bone marrow, but acquiring stem cells from adipose tissue is much easier and most patients have adipose tissue readily available ... The next step [involves] identifying and developing the growth factors that will induce transformation of cells more quickly. [Researchers are] also starting to use smooth muscle cells for tissue engineering in the urinary tract, including the urethra."
As researcher John Schloendorn notes over at the Immortality Institute, the portion of the LysoSENS research program based in Tempe is actively recruiting: "We offer: the opportunity to truly make a difference and bring SENS (Strategies for Engineered Negligible Senescence) research forward. Flexible conditions: Your responsibilities will reflect your qualifications; apply to come for weeks, months or permanently. Cutting edge working environment and a reputable entry on your CV. Research credits for a degree at Arizona State, if you are pursuing one. If elsewhere, you can probably get this work accredited, too. Enabling financial support, but no competitive salary. We want: The motivation to make personal sacrifices in order to help with curing aging and experience in molecular biology." It is good to see growth in the first SENS research project funded by Methuselah Foundation donors.
MIT Technology Review's 'SENS Challenge' is an invitation to mainstream gerontologists, with a $20,000 incentive, to compose a denunciation of SENS powerful enough to convince an independent expert panel that discussing SENS in detail - let alone funding it - is unwarranted.
The Technology Review received three submissions that were all rejected by the panel. Given the eminence of the panel in both biology and technology - and of the submitters in biogerontology - a popular conclusion is that it was singularly unwise of some of my colleagues in gerontology to be quite so outspoken in their opinions of SENS given how poorly they had in fact studied it. A second conclusion is that there was merit on both sides, since the panel were certainly not convinced that SENS would succeed.
I concur with the first conclusion, but sharply disagree with the second. My view is the exact opposite: that the detail of SENS is what makes it feasible. Hence a panel who came in with essentially no knowledge of SENS and studied it only quite briefly would be almost certain to doubt its feasibility. That they accept its admissibility as a credible topic of discussion *despite* harbouring such doubts makes their refutation of the position of my more intemperate critics even stronger.
However, it is not my purpose to be in any way triumphalist. I feel that no time should be spent flagellating my colleagues with the SENS Challenge's demonstration that their judgement in signing up to a denunciation of SENS was unduly hasty and short-sighted. Everyone makes mistakes; and the best course, here as always, is to learn from them but not to dwell on them. There are, to be sure, a rump of genuine SENS opponents (as opposed to skeptics) who have nailed their colours so firmly to that mast that they may have no choice but to bluster on to oblivion. The field in general is not so narrow-minded as to ignore the view of minds so eminent as the SENS Challenge panel, however. There is much work to be done to implement SENS, and the time to focus on that work is now.
The forward impetus towards meaningful healthy life extension research - as exemplified by the Strategies for Engineered Negligible Senescence (SENS) approach - is echoed in the mission of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging and the intent behind the Longevity Dividend proposal. Both are recent developments that I cannot see having happened even as recently as five years ago.
A sea change is in the making. Each new day in which the science and ethics of SENS are successfully championed and defended shifts the conversative mainstream of gerontology towards this productive position: that we could be moving towards the defeat of age-related frailty, suffering and death far more rapidly and directly than is the case today.
Researchers have made progress in recent years in identifying and understanding the mechanisms of decay and inefficiency in the aging immune system. Here, 50connect.co.uk looks at other threads in this work: "the most abundant form of white blood cells, whose job it is to defend against invading microbes, are only half as effective in people aged over 65 as they are in younger people ... What is particularly exciting about this finding is that in laboratory experiments we can improve the efficiency of white blood cells by adding DHEAS. We are now going to explore whether treating patients with this hormone can help them fight infections." Another study finds that "cells from older people had fewer receptors to direct the T lymphocytes to where they are needed, than younger people. This deficit resulted in less T lymphocytes reaching the infection site. ... older people have a specific immune response deficit in their skin, not necessarily a generalised lack of immunity."
As noted briefly by Medical News Today, scientists are making progress towards the first therapies for the accelerated aging condition progeria (HGPS): "HGPS is caused by a mutation in the Lamin A gene (LMNA) that results in the synthesis of a mutant prelamin A (also called progerin). Progerin undergoes farnesylation but cannot be further processed to mature lamin A, a key structural component of the cell nucleus. In HGPS cells, progerin accumulates at the rim of the nucleus, causing misshapen nuclei. ... [researchers] suspected that protein farnesylation might be crucial for the aberrant targeting of progerin to the inner nuclear membrane and were able to show that blocking farnesylation with an inhibitor would prove therapeutic." Given that the same cellular problems are seen to a lesser but still significant degree in "normal" aging, it seems likely that any successful progeria therapy would also prove beneficial for the rest of us.
A thousand and one people out there in the world are trying their hardest to convince you they have a silver bullet that will prevent, slow or cover up aspects of degenerative aging. From the perspective of the radical life extension that will be possible in the years ahead, none of these folk are selling anything worth a damn.
Sure, there are a few modestly effective ways to cover up some outward-facing results of age-related damage. But why spend your resources there when (a) everyone knows what lies underneath anyway, and (b) you could be helping progress towards medical technology that would actually repair that same age-related damage?
Sure, some modern therapies are fairly promising when it comes to patching up some of the hundreds or thousands of age-related conditions that result from accumulated cellular damage. But the development of new patches and the patching process is always too slow, too late, too expensive - and it fails all too soon anyway, because the underlying causes were not tackled. Present approaches are wonderfully better than nothing for those who suffer, but are as nothing in comparison to the methods and medical technologies that could blossom in the near future.
Sure, calorie restriction and a number of related lifestyle choices will reduce the rate at which you accumulate cellular damage - thereby extending your healthy life span and greatly reducing your risk and cost of suffering common age-related disease. If you're smart, you'll make use of these strategies ... but you'll be just as dead in the end if we don't progress far further in medicine.
The point which often goes undiscussed by the CR folks, most biogerontologists, longevity gene fans (including people such as Sinclair and Guarente who are really studying the mechanisms by which CR works), centenarian researchers, most "anti-aging" physicians, etc. is that with these approaches the animals (and people) WILL STILL AGE and WILL STILL DIE! This approach does nothing but slow down the rate of aging -- it does not stop it or reverse it.
The sensible approach to what little benefit we can gain for health and life span today is illustrated well, I think, in this post from Eric Boyd:
I need to carefully consider how long I figure I need to live in order to benefit from SENS type interventions. I figure that without interventions, I should be healthy up to about age 70, plus maybe 10 more years in an increasing frail state. This gives me 40 years of further progress in medicine. Assuming we don't get started on SENS (i.e. addressing the causes of aging via an engineering approach) for another 5 years or so, that gives me 35 years of progress before I am 'desperate'. I would like not to have to take the risks and expenses of being a first-generation-treatment taker, which likely means that I have to lag state-of-the-art by 10 years to feel comfortable, and that means only 25 years of progress. That is not enough - given what I know about even fairly simple things like drug development and testing, I expect that real anti-aging interventions will take decades to develop, so 25 years will just be the beginning of results.
CR could theoretically add 10 to 20 years of extra vitality of my life, which is more than enough to make a substantial difference. For this reason I will be implementing a system over the next few years
In other words, you are not the cricket grasping at the now. Rather, you are the ant who plans ahead.
We are close to real, working anti-aging medicine, after all - with the right level of public support and investment in research. It all brings to mind nothing quite so much as the fable of the lazy cricket and the industrious ant - although this may be somewhat unfair on the crickets in this case. My point is this: if you find yourself playing the role of the cricket, looking for necessities at the last minute in any aspect of life, then you are likely out of luck. Nothing in this world happens without preparation, hard work and a sound recognition of what the future will bring. The winter of age-related degeneration approaches for us all - indeed, we have a very good idea as to when it will arrive. We cannot wait until aging hurts and incapacitates us to search for medicines that will repair the damage to our bodies and enable us to live longer, healthier, active lives. If we wait, if we laze rather than work to ensure that the right research is funded, then it will be too late in the decades ahead. We will suffer, become crippled, and die.
Do you save for your retirement? I'm sure you do if you're of working age. If you can look that far ahead for financial matters, why are you not also investing a similar level of resources to ensure that you will not be crippled by age-related diseases? Be an ant. Don't be a cricket.
A silver bullet for degenerative aging will exist one day - if we all pull our weight and help to make it happen. It will take the the form of multiple therapies, repair and preventation technologies for different modes of age-related damage. It will be comparatively limited and expensive at first, but then improve rapidly in reliability and cost, as do all new medical technologies.
Will the first meaningful anti-aging technologies arrive within our lifetime? We - all of us alive today - will determine the answer to that question through our actions and choices. Be an ant, not a cricket.
As research into the mechanisms of healthy life extension through calorie restriction (CR) continues, the skeptics are finding their feet: "Calorie restriction is known to increase lifespan in many but not all species and may perhaps not do so in humans. ... Given the variety of physiological responses to variation in food supply that are possible, evolutionary life history theory indicates that an increased investment in maintenance in response to resource shortage will not always be the strategy that maximises Darwinian fitness. Additionally, for the well-studied species in which life extension is observed, there is considerable variation in the response. This suggests that it is not an ancient ancestral response, which has been conserved across the species range." For all that, the positive benefits on human health and resistance to common age-related diseases have been quite amply demonstrated.
I'm sure you all recall the recent $20,000 SENS Challenge results and the ensuing high-quality commentary from the healthy life extension community and wider blogosphere. SENS, the Strategies for Engineered Negligible Senescence, is an engineering approach to preventing and repairing the root causes of degenerative aging. The approach - and the underlying points that aging is the biggest problem we face, and that we know enough now to make good progress within our lifetimes - is garnering increasing support and interest.
By way of a reminder, you can find the various challenges, responses and counter responses at the Technology Review website.
Since the results were announced, Michael Rae - calorie restriction advocate, MPrize supporter and Aubrey de Grey's research assistant - has taken the time to prepare a fairly lengthy and detailed reply to the counter response provided by Estep et al. It's densely written and point by point, but if you've been following the debate you should certainly read the whole thing. Casual readers may want to scroll down to find the link to Chris Hibbert's analysis, which is written in more of an essay style.
I will briefly say that Mobbs's reply seems to be redundant to his original, which was already pretty weak, and intentionally ignores the specifics of Aubrey's reply; Weinstein's is too vague to be taken seriously, not presenting any evidence or seriously engaging the arguments, EXCEPT for his more detailed presentation of his histological disordering argument, which should've been made in his original rather than presented in argument to Aubrey's rejection thereof; and that Estep et al's reply was, as the judges rightly said, the most cogent. It's unfortunate that there is no mechanism for a direct counter-counter-rebuttal; here, I offer a somewhat informal attempt at the same.
Estep et al then make an attack on the Wright Bros. analogy. This would require an essay in itself to disentangle. The key points are that (a) de Grey is not claiming that we could do engineering with NO basic research, but that in the specific field of biogerontology, basic research has progressed to the point that no FURTHER basic research is required to devise a second-order, engineering solution to aging (with the "life-expectancy escape velocity" caveat mentioned above); and that (b) de Grey is entirely in favor of "every critical component of [SENS] be[ing] rationally designed and repeatedly tested" on exactly the same basis that the Wright Bros. tested their plane: *build* the thing, first plank-by-plank/component-by-component (as an intervention against a specific kind of damage and an ensuing disease state) and then as a complete platform (to reverse aging), testing them individually and then in unity. Given more time, one-to-one analogies could be drawn between various plane components and various specific SENS interventions.
For further reading, I recommend this equally lengthy analysis from Chris Hibbert:
In their response, Estep et. al. point out that the Wright brothers used the scientific process to test and evaluate the components they were building, and that they were systematic in their efforts to evaluate all the effects that mattered in getting into and remaining in the air. This response completely misses the point. Estep et. al. think that progress is made by systematically expanding the frontier of what is known. de Grey proposes to take what is known and build an effective mechanism to solve a problem, learning as he goes. The relevant question is whether we know enough at this point to start the process. The Wright brothers didn't know the answers when they started. They weren't satisfied with asking all the interesting questions, either; they asked the questions that were blocking their path to building a successful flying machine. Useful questions for critiquing an engineering proposal include: Do we know enough to get started? Is the cost estimate reasonable? Are there reasons to believe that there is no solution to the problem (within the budget)?
Overall, I have to agree with TR's panel. Estep et. al. may have found some holes in de Grey's specific proposed therapies (it's hard for me to tell; unlike de Grey, Estep et. al. don't provide layman's versions of any of their technical arguments), but they didn't show that these holes make the entire effort unlikely to succeed, and they didn't show that de Grey's proposal doesn't address a useful goal.
Again, you'll find a great deal more there to think about; go and read the whole thing.
A typically mixed article on healthy life extension from the Times Online: "But while headlines trumpet about modern-day Methusalahs, philosophers, sociologists, anthropologists and the public are beginning to ask a vital question that the scientists may have forgotten: are we getting so carried away with the possibility of extended life that we're forgetting to ask whether we want it?" Who is this "we?" Be very wary of people who use this sort of language; they are almost certainly trying to stop you from exercising your freedoms - such as the vital freedom of research. "The leading medical charity the Wellcome Trust takes the bull by the horns next week with a debate on whether science has looked at all the angles when it comes to living a full, long life. Speakers will examine the implications on lifespan of, for example, stem-cell technology for rebuilding damaged organs and our growing understanding of the molecular and cellular processes that lead to age-related disease."
Many people in the world hold doctorates, and a large percentage of the folk you see mentioned here and at the Longevity Meme fall into this category. As a general rule, I don't accord these folk their titular prefix when writing about them. Interestingly, no-one has ever asked why this might be so; for a change I'll beat the readership to the punch in answering a question.
These are a few of the reasons why:
1) People assign far too much weight to a "Dr." in front of the name, especially when glancing through an article at speed. I'd much rather readers were forced to spend that additional time to read the context and make up their own minds as to the merits - or that the expertise represented by "Dr." was better explained and characterized.
2) There are any number of different ways one can become a "Dr." Most are entirely irrelevant to whatever the matter at hand might be; even academics are far better defined by their present efforts and recent experience than by a few years of unrelated work for a doctorate awarded a decade or two ago. If you must have some form of shorthand, it's far better to describe someone by their recent history and function: researcher, gerontologist, statistician, advocate, and so forth.
3) A number of people in the broader healthy life extension community have obtained their doctorates in ways that appear traditional but are somewhat dubious on closer inspection. In some cases I'd rather not enhance their reputation, in others I just don't want to be put in the position of judging absent full knowledge. Other folk have obtained their doctorates in ways that are exemplary and reputation-making but non-traditional; I'd rather not get involved in the name-calling that goes on over that sort of thing. People will be people, but again the objective is to present information about the relevant expertise and experience of the person in question rather than their paperwork.
4) It doesn't take anything more than hard work and financial sacrifice to obtain a doctorate in any of the honest ways. The baseline effort required is nothing special - there is no doctoral spark. People who are truly innovative and have performed amazing, breakthrough work wind up with a doctorate that looks exactly the same as those of average workers who slogged their way through the process. The same letters wind up in front of their names; a doctorate is not a helpful way of picking the luminaries from us folk of lesser means.
5) I think the concept of showing respect through the use of a title is flawed. It's akin to giving Hallmark cards - the substitution of a mass-produced and somewhat lifeless set of choices for your own creativity and decision making process. You should be able to decide for yourself whether and how to be respectful. If someone demands respect through the use of a title, then the odds are good that they don't merit it - or that they don't understand what it is they might actually be respected for, which amounts to much the same thing in my eyes.
Finally, if I'm going to drop the title for anyone, I'll drop it for everyone.
Technorati tag: blogging
(From the Harvard University Gazette). Life expectancy statistics can provide a number of apparently counterintuitive points; for all it appears a straightforward enough concept, it is not: "Life expectancy in this country has been rising steeply since 1990, and the National Center for Heath Statistics concludes that the older you are today, the greater the age you are likely to reach. Men and women who make it to age 75 in 2006 can expect to still be around in 2016 and 2017, respectively. At age 85, the odds are good that you'll reach 91. ... people who study aging trends believe that life expectancies for the old will continue to grow longer. The main reason is that the three biggest killers of older people - heart disease, cancer, and stroke - are being treated more successfully." These are the results of the first impact of modern biotechnology on therapeutics. It can get much, much better - if the funding is there for directed research into repairing the cellular damage that causes age-related degeneration.
Kevin Perrott pointed out a presentation prepared for the White House Council on
Aging 2006 - an event I hope I was sufficiently dismissive of - at the behest of the Alliance for Aging Research and AFAR: "Scientists say the field is on the threshold of a new way of thinking, shifting focus from specific illnesses to searching to understand aging itself as a biological process. The report suggests that many of the scientists' concerns about the public's understanding of these issues emanate from political arguments or media coverage rather than actual public opinion at large. For example, researchers are generally pessimistic about public support for funding, but the research suggests the public seems to be far more supportive of basic aging research than the official political voices might lead scientists to believe."
Scientists are pulling more data in to demonstrate apparent systematic differences in the biochemistry of aging between people of different socio-economic groupings.
People in lower social classes are biologically older than those in higher classes, according to research. A study of 1,552 volunteers revealed a low social status can accelerate the ageing process by about seven years.
The UK/US team analysed key pieces of DNA called telomeres which are thought to correlate to biological age.
researchers looked at 17 pairs of identical female twins, who had begun life in the same socio-economic class but were currently in different social groups.
They found on average, the telomeres of the twin in the higher social class were significantly longer than those in the lower social group - the difference equated to about nine biological years.
This obviously begs the question 'Why?'
"The theory we have come up with is that it is related to the stress of being in that social status compared to someone who is not in that social status.
"The strain of being in that job, the effort-reward imbalance, self esteem and just generally the psychological stress of having lots of areas you cannot control in your life are perhaps more important than we have realised."
He said this may have a biological impact on the body, making cells divide more quickly and reducing the telomere length.
The scientific term for those last points would be "outright guesses." Looked at more closely, this seems to be a case of knowing enough to aptly demonstrate that you don't really know enough. Socio-economic status is correlated with all sorts of line items - wealth, education, intelligence, and so forth - that are themselves strongly correlated with health and longevity. In many of these cases, it's far from clear that anyone has presented a convincing answer as to which side of the correlation is causative, and to what degree. It may be a feedback loop rather than straight causation, and most likely varies from case to case and time to time as well.
There is a large and persistent association between education and health. In this paper, we review what is known about this link. ... We suggest that increasing levels of education lead to different thinking and decision-making patterns. The monetary value of the return to education in terms of health is perhaps half of the return to education on earnings
The original form of the telomere theory of aging - that reductions in telomere length alone are the principle root cause - is pretty much abandoned at this time; some studies even suggest that telomere length and life expectancy are not coupled:
This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for.
For a long time scientists believed [that] the length of our lives was meted out in our telomeres - the protective caps at the ends of the threadlike chromosomes that carry our genes. But life is never as simple as legend, and most researchers have abandoned the telomere theory of aging. They haven't given up on telomeres, though. Scientists are now testing whether degradation of these termini heralds the maladies associated with growing old, such as heart disease, dementia, and cancer. Understanding the association between telomeres and disease could lead to better treatments for cancer or new ways to stay healthy as we mature.
There an answer in there somewhere - but I think it's very bold and early to be jumping into this mess of correlations with any particular explanation. It would be good to run the whole study again with better biomarkers, say. Even better than that, recognize that time is far better spent acknowledging that we're all suffering from a condition that will deliver suffering, pain and death - and then doing something about it rather than simply observing it.
The Methuselah Mouse Prize is the premiere effort of The Methuselah Foundation; a scientific competition designed to draw attention to the ability of new technologies to slow and even reverse the damage of the aging process, preserving health and wisdom in a world that sorely needs it.
The Guardian notes that Zig Zag's documentary on cryonics will be aired in the UK. "The first ever footage of a person being cryonically frozen is to be broadcast in a Channel Five documentary that will follow a woman who is terminally ill with cancer before and after her death. ... We're really very proud of what we have achieved with this programme - the human and emotional journey we captured with one contributor in particular, filming prior to her death and the subsequent process of her preservation, in conjunction with the amazing scientific and ethical questions raised by this subject, makes for one of our most challenging and fascinating productions to date." Filming was earlier this year, according the Alcor newsletter; I'm hoping this turns out to have more of a respectful positioning than the Guardian article suggests. Cryonics is an essential insurance policy; the best and only option available to all too many people who will die before the onset of meaningful healthy life extension technologies.
Via EurekAlert!, recent research in which biomarkers of cellular aging - genetic activity in this case - and programmed aging are discussed in the same breath. In fact these are quite separate topics; programmed aging is not necessary to explain common forms of change in gene expression with tissue age, nor longevity differences between species. "Why animals and even people age at different rates prompted Kim to look deeper into the processes that control aging. His new study suggests that the cell has a molecular homeowner that keeps up repairs until a predetermined time, when the owner picks up the welcome mat and moves out. Once that process kicks off, the decay happens as a matter of course. The homeowners in tortoise cells stick around for hundreds of years delaying the decay, while those in fly cells move out within weeks ... [the] work doesn't identify what triggers that process, it does provide a way of detecting the point a cell has reached in its life span." Remember that cellular longevity doesn't necessarily have to have anything to do with your longevity.
A great deal more than DNA sequencing is going on in the bioinformatics field, but the cost of sequencing seems to have become the chip speed of that industry - a commonly used measure for present capabilities and speed of progress. "The goal now being pursued by the N.I.H. and by several manufacturers [is] to drive the costs of decoding a human genome down to as little as $1,000. At that price, it could be worth decoding people's genomes in certain medical situations and, one day, even routinely at birth. ... As we drop the price and increase the capability, there are applications that couldn't be done before, [like] a researcher being able to screen a thousand patients for cancer mutations." We're heading for a real influx of information; vast, ever-growing databases to accelerate medical research and spur development of new technologies to engineer longer healthy life spans.
Medical News Today provides surprisingly good news about a common age-related condition: Frontotemporal Dementia (FTD), "the second most common form of dementia after Alzheimer's disease, is a group of brain disorders that affect the frontal and temporal lobes of the brain ... What we've found is a little bit different than what we've found in other common neurodegenerative diseases. What we're looking at here is simply the loss of progranulin that is causing the disease ... One copy of the progranulin gene has been knocked out by the mutation, and therefore we have less progranulin produced, which is enough on its own to cause the disease." We don't expect neurodegenerative conditions to be easily prevented or cured - but every so often something goes our way. "Replacing progranulin is the obvious therapeutic approach ... That might be possible through gene therapy."
There are all sorts of bad, mistaken or plain malicious reasons that people give when opposing healthy life extension research - which means being all for suffering, pain and death by age-related degeneration. Perhaps they think that future longevity technologies would lead to increased, longer frailty (the Tithonus error); or that Malthusian predictions of doom by overpopulation will finally be right after all these centuries of being flat out wrong (fat chance); or that a longer life would inevitably lead to boredom; or economic ignorance leads them to oppose the conditions necessary for progress in medicine; or that present day attempts to engineer longer, healthier lives "defy nature" more than those of past centuries; or they romanticize of death and aging as somehow noble, papering over mess, suffering and horrors; or perhaps they are possessed of a deeply ingrained sense of self-loathing.
At the base of it all, I think, is a deep and profound fear of change. Some people would rather embrace any present horror than even the most positive change. This is not one of the better traits we humans seem to have hardwired in our evolutionary heritage. On that note, a very illustrative op-ed was pointed out to me today; it speaks volumes of the mindset that justifies a continuation of today's death and suffering into tomorrow.
There's a lot of talk about anti-aging research today, but with all the promises of longevity and even immortality, almost no one has apparently considered the consequences of human beings living forever. The more you think about it, the scarier the idea becomes.
Think of the people who currently hold power in medicine, pharmaceuticals, media or government. Imagine if they never died. In fact, if you think about it, one of the best things about some people is the fact that they will eventually be six feet under.
Science would never have advanced if the old-school high priests of science lived forever. And society as we know it today will never move forward unless the cronies currently in power someday keel over and die (harsh, but true). This is why I say a civilization that could give its population the ability to live forever would be doomed to eternal stagnation. Mortality is an important component of any successful species.
All complete nonsense, of course. I'm going to go out on a limb here and propose that ignorance lies at the root of fear of change: ignorance of the way in which change occurs; of the way in which people act to create change; of common timescales of change; of the degree to which change is occurring around us all the time. How can anyone look around the world today and propose that the present breakneck pace of change will somehow grind to a halt if people live longer? Major technological and cultural change is occurring on timescales of a decade; it should be rather hard to deny that in the face of the internet and biotechnology revolution, let alone everything else that is 2006 rather than 1986.
It is deeply disturbing that so many people believe that death - rather than personal growth and change - is the only thing driving progress. Destruction of health and life is nothing but destruction: those billions of unique individuals could have contributed, changed, built new things, accomplished new goals. The structure of our lives today is forced upon us by the all too rapid decay of our bodies; we simply don't have enough time to be anything more than the merest hint of our true potential.
The stagnation argument against radical life extension - illustrated in the quote above - is just as bankrupt as the other arguments for the death and suffering of billions, and just as widely dismantled and demolished. Nonetheless, it persists, just as the others; they are a displacement activity, resistant to logic, the cry of people who would rather suffer and die - would rather everyone else suffered and died - than change. If that is their choice, then they should be free to make it for themselves - but fought every step of they way should they work towards removing our freedom to engineer the longer, healthier life that we desire.
Technorati tags: life extension
It's good to see that the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging is already appearing on published research. Via PubMed: "Eukaryotes have evolved elaborate mechanisms to survive periods of adversity. By manipulating genes that control these mechanisms, researchers have found they can generate more stress resistant, longer-lived organisms. One of these is the PNC1 gene of [budding yeast], a master 'longevity regulatory gene' that translates a variety of environmental stresses into lifespan extension by activating the sirtuin family of longevity deacetylases. ... We propose that there is a functional equivalent of PNC1 in mammals called Nampt (a.k.a. PBEF/Visfatin), a stress-responsive gene that would coordinately regulate metabolism, cell defenses, and resistance to diseases of aging." There are those who see this sort of metabolic research as a dead-end: interesting and useful within its range, but not likely to produce ongoing significant healthy life extension.
The following is something of a cliche: scientists investigating genetics or biochemistry find a way to shorten life span in laboratory animals. They end their publication with the declared hope that further investigation will find a different manipulation of the same process that will extend life span. Here is an example of the type:
Scientists first noticed connection between aging and circadian rhythms in mice bred to lack a gene known as BMAL1.
Marina Antoch, a molecular biologist at the Lerner Research Institute in Cleveland, Ohio, and her team observed a group of 30 BMAL1 knockout mice. The knockout mice lived only half as long as 30 normal mice did, the researchers found. They also found that the knockout mice aged at an accelerated rate: By 18 weeks of age, the knockouts had lost a significant amount of fat, muscle, and bone mass. They also exhibited organ shrinkage in their spleens, kidneys, hearts, lungs, and testes--all signs of aging. And, like older humans, the BMAL1 mice lost hair and developed cataracts in one or both eyes.
Further experiments showed that mice lacking BMAL1 had anywhere from 10 to 50 percent higher tissue concentrations of harmful reactive species of oxygen and nitrogen, which are associated with the aging process. This finding suggests BMAL1 may help stave off aging by preventing the build-up of these species, says co-author Roman Kondratov, a molecular biologist also at the Lerner Research Institute.
"I think the next step is really tying this observation to the clock function of BMAL1," says cardiologist Garret FitzGerald of the University of Pennsylvania School of Medicine in Pittsburgh. If there is a functional link, he says, we may someday be able to manipulate our circadian clocks to prevent the ill effects of old age.
Whenever you see an article like this, mentally replace the biochemical process at hand with "blunt trauma" or "acid ingestion." You can certainly shorten life spans that way, but you are unlikely to find a way to extend longevity through the use of hammers and sulphuric acid.
You should also bear in mind that the appearance of accelerated aging is by no means an indicator that accelerated aging is in fact taking place. It was something of a big deal that certain human accelerated aging conditions were shown to actually be accelerated aging, for example. As another example, diabetes looks a lot like faster aging in many respects, but it isn't.
Surprisingly few biochemical processes are open to this sort of "let's find out how to throw it into reverse" logic, but the funding game requires one to pitch the next proposal ahead of time and on the basis of your latest research. Playing on past odds, I'd wager no significant healthy life extension will result from this research. The real payoff for this research will be a greater understanding of genetics, metabolism and cellular biochemistry - a noble goal in and of itself, but not a pitch that is likely to win friends and influence funding, sad to say. There is no useless knowledge in this space, for all that some paths forward seem more likely to pay off in longevity than others.
Researchers continue to quantify the level of risk linking diabetes and Alzheimer's: "failure of diabetic patients to maintain control of their blood-sugar levels increased their risk of developing dementia 10 years down the road by as much as 78 percent ... Glycosated hemoglobin - known as HbA1c - kept under 10 percent in the blood appeared to be the point where the likelihood of developing dementia begins ... [another study] described how patients with borderline diabetes were 67 percent more likely to develop dementia nine years after diagnosis and were 77 percent more likely to develop Alzheimer's disease after nine years." Diabetes appears to be a condition most people could avoid; if you let your metabolism and lifestyle slide into causing more cellular damage, it shouldn't be a surprise that you suffer more rapid and greater age-related degeneration.
Via the Financial Times, another reminder of the importance of reducing chronic inflammation and the damage it causes: "in old age, a failing immune system frequently triggers inflammation in many parts of the body. This in turn causes chronic disease. ... There is a strong inflammatory element in all the major diseases of ageing. The body tries to adapt by producing anti-inflammatory compounds [but] human biology eventually fails. ... Our immune system has evolved to get rid very efficiently of acute infections in young bodies but it has not been selected to get rid of subclinical viral infections in old age. ... The constant attempt to suppress slow-acting viruses such as cytomegalovirus (CMV) could eventually throw the immune system out of balance ... CMV is a passive infection in many old people - and more and more of the immune system is devoted to fighting it."
Forbes reports on interesting research into metabolism and inflammation: "Called aP2, the protein has no useful function in the body. It only appears during the course of disease, and seems to cause adverse effects on blood sugar levels and fatty acid metabolism. It previously has been found in fat cells and macrophages (a type of immune cell) in people with obesity, diabetes and heart disease. ... [researchers have] found aP2 in the lining of the human lung, where it appears to regulate the inflammation associated with asthma. ... To study the effects of aP2, the researchers created genetically engineered mice that could not produce the protein. ... They're metabolic supermice. We cannot make them obese, diabetic or atherosclerotic. They don't develop fatty liver disease, and they don't develop asthma ... pharmaceutical companies have developed aP2-blocking drugs. ... They work very well in animal models and produce the same effects we've seen in genetically engineered mice. But all the work is pre-clinical."
The transhumanist community and news site Betterhumans has moved into the latest of its recent redesigns. As you might expect, I'm pleased to see items from the Longevity Meme daily news gracing the front page - the feed is there to be made use of, after all.
On much the same note, and as I'm sure a number of you have noticed, I have been crossposting some Fight Aging! posts to Betterhumans of late. Given the size and interests of our community, it wasn't obvious to me that this would actually result in anyone new reading more about healthy life extension research and activism. As it turns out, however, this was a successful experiment in broadening the audience. I will continue to crosspost as the fancy takes me.
I consider broadening the audience to be a worthwhile and very necessary endeavor, although any significant broadening is going to happen largely as a result of new folk jumping in to write about healthy life extension. We can never have too many new voices to swell the conversation and help raise awareness and support for meaningful scientific research aimed at extending the healthy human life span. Broadening one's own audience really can't be done haphazardly, however - a little thought needs to go into how to spend the effort. It's all too easy to wind up missing opportunities, talking to the unreceptive, or talking to no-one at all. I turned down a spot in the launch of Seed's ScienceBlogs, for example, and I think that's looking like the right decision. Individual blogs are becoming increasingly buried, you're locked into someone else's publishing platform, and I would have had to give up generous advertisers who donate to the MPrize and appearing in Google News via the MPrize website. Not that Seed isn't offering a good package for a certain type of blog and blogger - it's just that Fight Aging! are I are not it.
If you take one thing away from this rather self-indulgent and rambling post it should be that you have a voice - and making yourself heard online is essentially free beyond the time you spend doing it. If you're clear and passionate about healthy life extension, and post consistently, you will receive links and attention - and thereby add to the level of awareness and support for the fight to cure aging. This is a good thing; more people should be doing it.
Since cancer stem cells - and the implications for future cancer therapies - seem to be the topic of the moment, I should point out this news of progress from EurekAlert!: researchers "have isolated rare cancer stem cells that cause leukemia in a mouse model of the human disease. The leukemia stem cells isolated proved to be surprisingly different from normal blood stem cells - a finding that may be good news for developing a drug that selectively targets them. ... scientists showed that they could create leukemia stem cells, which also are self-renewing, from partially committed, non-self-renewing progenitor cells. The latter are short-lived cells that can turn into several types of blood cells ... in the future we should be able to specifically target leukemia stem cells without killing normal stem cells."
The politics of stem cell research are underway in earnest once more in the US, for what it's worth.
With just days to go before the Senate is scheduled to vote on a hotly anticipated bill that would loosen President Bush's restrictions on [Federal public funding for] human embryonic stem cell research, both sides of the scientifically and ethically charged issue have ramped up their publicity machines and attacks on each other.
At least they're largely fighting over what to do with taxed dollars, rather than fighting over whether to ban these very promising medical technologies. That's a step up in the sense of falling into a pit versus falling into a pit with spikes at the bottom.
Given my leanings, I'd rather see a world with much more research funding that has not been taxed and wasted by government before it gets to the laboratories; a world in which funding research is a matter of personal choice and spontaneous organizations such as the Methuselah Foundation. This is conceivable, workable, but it'd take a lot to get there.
As for many other large, desirable changes for the future, my first things first pragmatism leads me to help longevity research - and research likely to lead to cures for age-related conditions - prior to helping found a more libertarian society. Or indeed helping any of the other causes I consider worthy. First things first: it's hard to help when you're suffering or dead, and little will have a greater effect upon the degree of suffering and death in the world than success in healthy life extension research.
But back to the ostensible subject of this post. One of the many line items in this morass of politics that I find so distasteful is the outright lying on scientific topics. There are any number of people out there willing to misrepresent the state of present day stem cell science until blue in the face, just to gain some meaningless advantage in debate, or to make themselves feel better. This usually takes the form of denigrating embryonic stem cell research, or overhyping adult stem cell research - but the lies are pretty baldfaced these days.
"Prentice not only misrepresents existing adult stem cell treatments but also frequently distorts the nature and content of the references he cites," wrote Shane Smith of the Children's Neurobiological Solutions Foundation in Santa Barbara, Calif.; William B. Neaves of the Stowers Institute for Medical Research in Kansas City, Mo.; and Steven Teitelbaum of Washington University in St. Louis.
For example, they wrote, a study cited by Prentice as evidence that adult stem cells can help patients with testicular cancer is in fact a study that evaluates methods of isolating adult stem cells.
Similarly, a published report that Prentice cites as evidence that adult stem cells can help patients with non-Hodgkin's lymphoma does not address the medical value of those cells but rather describes the best way to isolate cells from lymphoma patients and grow them in laboratory dishes, the letter said.
And Prentice's reference to the usefulness of adult stem cells for patients with Sandhoff disease -- a rare nerve disorder -- is "a layperson's statement in a newspaper article," the scientists reported.
All told, the scientists concluded, there are only nine diseases that have been proved to respond to treatment with adult stem cells.
"By promoting the falsehood that adult stem cell treatments are already in general use for 65 diseases and injuries, Prentice and those who repeat his claims mislead laypeople and cruelly deceive patients," the scientists wrote.
A look back in the Fight Aging! archives turns up a good overview as to why embryonic stem cell research is essential. I'm not sure why it is that these folk feel it is better to lie about science than to simply debate on grounds of belief and preferences - but it's pretty despicable. This is what the tragedy of the commons does to people. The commons in this case being that pool of taxed dollars; dignity, responsibility, accountability, common human decency and self-respect are the first to fall to the mud beneath this great trough.
Now that scientists are well aware of cancer stem cells, it seems they are being found everywhere. From MedlinePlus: "Primitive cells that resemble stem cells may help some ovarian cancer tumors linger and recur in the body, but it may be possible to subdue them ... The findings build on other studies that show leukemia, breast, brain and other tumors have so-called side population cells that resemble the healthy stem cells found elsewhere in the body. ... Cancer stem cells, like somatic stem cells, are thought to be capable of unlimited self-renewal and proliferation ... The majority of patients who respond to primary chemotherapy ultimately develop recurrent, usually drug-resistant, disease that is conceivably due to the ability of ovarian cancer stem cells to escape these drugs." Researchers believe they will be able to effectively target cancer stem cells with the next generation of therapies.
Age-related frailty and disease destroys wealth and the ability to build more wealth - and then costs more besides for care, as Forbes notes: "The estimated total worldwide cost of caring for people with Alzheimer's disease and dementia now tops $248 billion U.S annually. That estimate, based on a worldwide prevalence estimate of nearly 28 million people with Alzheimer's and dementia, includes a newly determined figure of $92 billion for informal care costs. That amount was combined with an earlier estimate of $156 billion earmarked for direct care costs." Compare this with the staggering, vastly greater costs of general age-related degeneration; trillions for each year. People have been persuaded to effectively fight Alzheimer's. Why then is it so much harder to persuade people to fight aging for exactly the same reasons?
That didn't take long.
I'm pleased to note that there are now 100 members of The Three Hundred, philanthropists of ordinary means who have stepped forward to support the Methuselah Foundation and the MPrize for longevity research. This is real progress: it's been little more than two years since the first of The Three Hundred; you'll find early thoughts way back in the Fight Aging! archives, as it so happens.
Given that successful organizations tend to show increasing growth with time, I'm confident that the next 200 members will arrive within the next two years - if we continue to work hard at it. So if you've been thinking of joining, why not join now? There may not be any room left by mid-2008!
Kevin Perrott, executive director of the MPrize competition, took a moment to look back in an Immortality Institute thread:
Absolutely bizarre to remember back to the fall of 2003 when I got involved with [Aubrey de Grey] and Dave Gobel... not even 3 years ago. I'm sure there are many here who remember a time on ImmInst when there wasn't an Mprize or a Methuselah Foundation. It's amazing how far we've come and how fast and quickly The Three Hundred are truly morphing into something like their namesake.
We will likely be making a much bigger deal of this just because it is a significant milestone to have achieved and a testament to the convictions of the volunteers and supporters of the Mprize and the Foundation but what's really great is that the fact that it was a milestone didn't matter to our 100th donor, he just wanted to help.
The Methuselah Foundation, generous donors and many other supporters in the community continue to do their part to ensure that the potential of serious, direct approaches to reversing age-related degeneration remain in the public eye. This foundation of advocacy and activism will be absolutely essential in the years ahead, in which much more significant funding will be directed towards healthy life extension research. Without widespread awareness and support for the defeat of aging, that funding simply will not be available.
We stand at the very beginning of the construction of a research infrastructure and culture of support for anti-aging research that will one day rival the cancer establishment in size and dedication. The more effective our support today, the sooner large-scale research into greatly extending the healthy human life span will get underway.
This release notes that TheraVitae, who have been providing a successful stem cell therapy for heart damage in Thailand, have established a subsidiary in Canada: "The Company will start clinical development of the lead product VesCell and will continue to develop additional products for cardiovascular and other severe disorders. Established in Toronto, Canada TheraVitae Inc. plans to submit regulatory requests to Health Canada and the FDA for a clinical trial of its therapy for congestive heart failure." The regulatory regime for medicine in America is oppressive, delivering nothing but delay and additional cost - and ensuring that innovators provide their services in other parts of the world. Ask yourself this: what are those who suffer and die of heart disease in the US really gaining through the years of delay and tens of millions of dollars imposed upon the deployment of demonstrably effective therapies?
The American Academy for Anti-Aging Medicine (A4M) has been quietly promoting the concept of a $1 million LEx / Life Extension Prize, already 1/3 funded by the look of it. Their objective appears to be to encourage the development of responsible anti-aging medicine through objective measure of performance. This is a laudable goal within their fraud-ridden industry and definition of anti-aging medicine (the prevention and treatment of age-related disease), but has the look of a project that needs further thought and definition. How do you define 20 years of reversal in the chosen biomarkers of aging? Do you acknowledge that reversal of the chosen biomarkers may have no effect on the underlying processes of aging - and may even reduce life span, as seems to be the case for growth hormone? You should read biomedical gerontologist Aubrey de Grey's comments to a Fight Aging! post on aging biomarkers, and a further discussion on the same the following year.
ScienCentral is running a gentle introduction to cancer stem cells and their significance: "cancer stem cells were first discovered in 1994. Since then, cancer stem cells have also been found in breast cancer, brain cancers, and prostate cancer. ... in addition to the published cancers, I know of four other types of cancer where the stem cell population has been identified ... Using a sophisticated instrument called a flow cytometer that sorts out stem cells from tissue samples, the researchers can also isolate cancer stem cells from tumors. Then they can test the cells' ability to form new tumors. ... What we found was as few as 100 of the cancer stem cells could easily re-form a tumor whereas tens of thousands of the other cancer cells were totally unable to form a new tumor." Researchers believe that attacking these stem cells with targeted therapies will be an effective new direction for cancer research.
I was prompted back to thinking about the present cultural norms of retirement and long-term financial planning by a couple of posts encountered while browsing the blogosphere:
What happens as we approach Strategies for Engineered Negligible Senescence, and beyond that, The Singularity? I think the short answer is that, at first you'll need a lot more money, and later not so much.
First of all, when SENS gets going, it will not be cheap. Intelligent people have already made the lifestyle changes necessary to add years to their lives, so when SENS comes along, they'll want to have it. Even now, clinics that specialize in hormone treatments with growth hormone and testosterone and the like can cost up to $10,000 a year or more, and the clinics are growing. Plenty of customers available who will spend that kind of money. SENS will likely cost a lot more in the beginning. And if you're chugging along on a Social Security check you won't be able to afford it. What this means is that not too far into the future, having an adequate amount saved for retirement can literally mean the difference between life and death.
Some time ago, I laid out guesstimates and rationales as to what you should be prepared to spend on the first generation of rejuvenation therapies that actually work. The numbers are intimidating until you realize that most people in a country like the US could, in fact, save and invest enough over a lifetime to afford it.
In 25 years, I'll be in my late 70s, right at the limit of current life expectancy for an American man, though by the time I get there, conventional medicine and scientific progress will no doubt have increased that somewhat. So the challenge is to make it that long in reasonably good health in order to be alive to take advantage of [robust human rejuvenation (RHR)]. As I said before, you're going to want to have a nice little pile stashed in your retirement accounts to be able to afford the first manifestations of RHR. It won't be cheap, although no doubt the prices will rapidly decline. On the other hand, new forms of therapy will continue to be discovered, and none of them will be cheap to begin with. And as I also said, those without sufficient funds and just on the wrong side of the aging curve will... die.
What else? Don't retire. Retirement can cause serious deterioration in mental and physical health. Now is not the time to consider it. Sorry. I know that if you're like me, you've dreamed and planned of retirement, getting away from that boring job, hitting the beach etc. A better plan would be to find a job that you like, and if that takes retraining, then do it, because after all you're going to live a very long time. Right?
It is a positive development to see more folk pondering these questions; the truth of convictions lies not in what people say, but rather in their long-term financial plans and actions. Growing awareness of the potential for gains in healthy life span and support for healthy life extension research will translate into changing investment and retirement planning when people are really, truly sold on this future.
As I've pointed out before, the medical technologies of decades to come are far from a sure thing for those of us old enough to have long-term financial plans in progress. They only surity here is that the more you save - and the better care you take of your health now - the more likely it is you'll be able to take advantage of the first real anti-aging medicine when it arrives. Fail to save, and you'll have pushed back your access to these technologies for the time it takes to go from first (expensive) entry into the commercial market to (cheap, reliable) widespread availability - which seems to be about 20 to 30 years these days.
I'm sure you can run the numbers on your life expectancy and just what a 20 to 30 year delay would do to your chances of using ever better medical technologies as stepping stones to an era of radical life extension. Fail to save and you're all too likely sentencing your future self to greater suffering and an early death.
Once you get there, however, why retire? Retirement as it presently stands is forced upon us by increasing frailty and the depredations of age-related disease. If you're healthy and active, why quit at a point after you've finally engineered your working life into something you enjoy and profit from? As things presently stand, people compress a lifetime of vacation into their final years precisely because they become unable to further grow their wealth through wages, entrepreneurial activities and other work.
The economic realities that drive the present culture of savings and retirement will be up-ended in the decades ahead, provided that medical science advances rapidly towards healthy life extension therapies. You are likely to have amazing options awaiting you in terms of exchanging comparatively modest invested wealth for additional healthy years of life - options that are presently unavailable even to billionaires. You should take a careful look at your financial plans for the future, and make sure you are prepared to catch the wave as it rises.
I've mentioned hormesis and longevity once or twice: a little stress on a biological organism tends to harden it up and make it live a little longer. This Biogerontology paper provides an example of the process in worms: "Mild hormetic heat treatments early in life can significantly increase the lifespan of the nematode C. elegans. We have examined the effects of heat treatments at different ages and show that treatments early in life cause the largest increases in lifespan. We also find that repeated mild heat treatments throughout life have a larger effect on lifespan compared to a single mild heat treatment early in life. We hypothesize that the magnitude of the hormetic effect is related to the levels of heat shock protein expression." This sort of longevity research is akin to metabolic investigations - interesting, probably somewhat useful, but ultimately nowhere near as helpful as other, more direct avenues of anti-aging research.
(From Pioneer Press). Entrepreneur and futurist Ray Kurzweil continues to do a good job in selling the commonsense fundamentals of futurism to the public: "Biological processes are essentially programming processes. We'll be able to reprogram biology and overcome major diseases in 15 years. ... In 10 to 15 years, we'll have this fantastic technology to slow down cancer and heart disease." Great gains in support for healthy life extension and other important goals can be attained by guiding people through the disconnect between what they know is true - rapid progress today, in other words - and what they have trouble visualizing: the consequent potential of exponential progress towards radical change and improvement within our lifetimes. I believe Kurzweil's timelines are optimistic - for reasons relating to human organizational inertia - but not by more than a couple of decades, absent bad scenarios.
It's not all biochemistry in the body: scientists are discovering that mechanical forces can have important effects at the cellular level: "Atherosclerotic narrowing and hardening of coronary arteries typically appear first at vessel branches, and a [study] reports that the type of mechanical stretching found at those branches activates a cellular protein known to damage cells. The report is the first to link mechanical forces with structural and biochemical changes in blood vessel cells that could explain why atherosclerotic lesions form preferentially at branches of coronary arteries. ... The cellular protein in question is called JNK, which is short for c-jun N-terminal kinase. The protein is a key barometer of outside stresses on a variety of cell types. Researchers are examining the role of JNK in many diseases because it regulates the expression of genes involved in programmed cell death, tumor genesis, and other stress responses."
Various folk have posted their opinions on the recent SENS Challenge results; a modest sampling follows.
I think this is a pretty good outcome. It should serve as a rebuke to those scientists who would rather name-call than think and test. On the other hand, it should also remind those of us who support de Grey that many of de Grey's proposals are beyond the ability of contemporary science to test. Not that de Grey and most of his supporters haven't already acknowledged that fact.
By necessity SENS leads contemporary science. But what great engineering projects have ever been started where the science was completely known ahead of time? Certainly not the Manhattan, Apollo, or Human Genome projects. The Human Genome Project was started knowing that it would take a century to complete with the computers and methods then available, but they went ahead with confidence that better computers and sequencing methods would develop during the project. They were right.
The details of Aubrey de Grey's SENS proposal are important - we have to start somewhere. But when (not if, but when) some detail of the present SENS proposal is proven incorrect, SENS will no more falter than any of those other projects when technical obstacles were encountered.
Nobody was able to claim the prize, although Technology Review's admission of that point is a bit mealy-mouthed:
LOL Translation: "nobody came close, but how BEAUTIFULLY written their failed arguments were!!!! And even if they lost, de Grey didn't win either, so nyah nyah nyah!!!"
I strongly encourage anyone with an interest in gerontology or life extension science to visit the lively debate at Technology Review concerning the "SENS Challenge", with a prize of US $20,000 at stake. The challenge was issued a year ago, with the $20,000 prize offered to anyone who could prove that SENS was "unworthy of learned debate."
No one is staking his life that SENS is correct in every detail. That level of perfection is not necessary for SENS to have a profound positive impact on anti-aging research. It is only necessary that the SENS theories help lead to positive results, either directly or indirectly, for the theories to have been worthwhile in the long run.
There are backwaters of science that need to be shaken up from time to time. Gerontology had certainly become one of those backwaters by the 1990s. The entry of SENS into the arena has been like a splash of cold water to the face, and like a breath of fresh air, simultaneously.
I'll try to read the three submissions and the back and forth between de Grey and their authors. I'd like to understand the best arguments for and against; I'm hopeful that I'll learn something more about the biology and the chances for SENS' success. I somehow suspect that as scientists criticizing an engineering proposal, they'll spend their time showing that his suggestions aren't proven. What matters is whether the proposals are close enough to right that they can be corrected as we learn more. That's much harder to justify in a new area, and also much harder to attack convincingly.
Back in August, Technology Review magazine issued another challenge - a prize of $20,000 for any molecular biologist working in the field of aging who could submit an intellectually serious argument that SENS is so wrong that it is unworthy of learned debate. Well this week an independent panel of judges decided that none of the three submissions received were worthy of the prize.
What does it all mean? I guess it means that, despite the derision aimed at Dr de Grey's theories from certain members of the scientific community, no-one has been able to provide a scientific rationale sufficient to convince the panel of judges that SENS is inherently flawed. Now, I'm no biogerontologist (hell, I can hardly spell it), but I'm all for backing any serious big brain (and, in Dr de Grey's case, a big beard as well) who thinks they might be able to delay, let alone cure, aging. Shouldn't this be the #1 field of scientific research?
The more people asking themselves that last question the better, I say.
SENS - the Strategies for Engineered Negligible Senescence - is undoubtably flawed in detail in some presently unknown ways, as was pointed out in some of these posts. All present day science is just the same - suffused in a sea of flaws and unknowns, within which lie the seeds of progress and new discovery. You don't need perfection to achieve great works; "good enough" is good enough for the engineering of significantly better, longer lives - and ongoing science in parallel will make progress ever easier.
SENS is far more than just scientific and engineering details, however. Beyond this, it is a compelling and persuasive vision of the organization and mindset required for progress towards the most important goal of our time: marshalling biomedical science to defeat age-related degeneration and death.
UPDATE 07/16/2006: You should read this one from Anne C. as well:
In some ways, I think that the Estep et al. submission highlights an apparent tripwire in the terms of the challenge itself. After all, how can one prove something to be "unworthy of learned debate" by engaging in learned debate? Nevertheless, I would still say that this is an apparent tripwire since Estep et al. could have chosen to simply go directly to the ideas presented in SENS and attack them on their (lack of?) technical merit. I think that the outcome of this contest serves as an important admonition to scientists that when they are told to criticize an idea, they focus on the idea itself and not an attempted psychoanalysis of those who propose the idea.
I will consider it a lovely day indeed when we have two or three different scientific / engineering proposals at hand, all focused on addressing senescence, and all relentlessly criticizing the ideas and methodology of the others.
Scientists continue to better coax multipotent stem cells from hair follicles, as noted by EurekAlert!: "Hair follicles are well known to be a source for adult stem cells. Using human embryonic stem cell culture conditions, the researchers isolated and grew a new type of multipotent adult stem cell from scalp tissue ... The mutipotent stem cells grow as masses the investigators call hair spheres. After growing the 'raw' cells from the hair spheres in different types of growth factors, the investigators were able to differentiate the stem cells into multiple lineages, including nerve cells, smooth muscle cells, and melanocytes (skin pigment cells). ... Although we are just at the start of this research, our findings suggest that human hair follicles may provide an accessible, individualized source of stem cells." A low-cost, reliable source of this nature would greatly speed the development of tailored regenerative repair kits capable of engineering new tissue on demand.
This PDF-format paper looks at varying aging theories and what they might mean for the prospects of developing medical technologies to halt or reverse age-related degeneration. "The feasibility of developing any such treatment depends on the existence of common factors involved in causing many or most of the manifestations. Further, in order to be 'treatable' a factor would need to be sufficiently independent of any function that we need to live happily in order that altering the factor did not cause significant adverse effects. Few would want an anti-aging treatment that resulted in blindness or some other major side-effect. The potential for the existence of treatable common factors is highly dependent on aging theories. Depending on which theory you believe, the likelihood of finding such factors ranges from 'impossible' to 'very probable'."
LysoSENS researcher John Schloendorn signed up as the 98th member of The Three Hundred today - welcome aboard! The Three Hundred is an association of generous folk of modest means, joining together in support of the best present day effort to encourage meaningful anti-aging research:
What's it worth to you to live 150 healthy years? What's it worth to you to raise the average human life span to 150 years, just for a starter? These are not idle questions.
We're looking for a few special individuals and organizations to make a meaningful, but affordable commitment: $1,000 a year, for 25 years, which amounts to $85 a month or $2.75 a day, the equivalent of one visit to Starbucks.
Our model is a classical one. It's based on another battle that saved the future of Western Civilization: Thermopylae. In 480 B.C., 300 Spartan warriors fought against incredible odds, so that the rest of Greece could mobilize against Darius's Persian hordes. Without their delaying action at the narrow pass of Thermopylae, the achievements of Greece and our culture as we know it would have been swept away.
The Methuselah Foundation is asking you to follow in the footsteps of this noble Three Hundred, not to risk your lives, but to provide some of your treasure, so that others may live ... and live ... and live, so that the human species can beat back not just an army, but the Grim Reaper himself.
This special group - strictly limited to 300 individuals or organizations - will live on in history just as the original 300 have, even to this day. You can be one of them.
We folk of ordinary means can band together to become philanthropists of note, changing the world for the better by funding the MPrize for anti-aging research. What price a future in which the old can live without pain, without disease, without frailty - in health and vigor? In each year that passes without the technologies of healthy life extension, tens of millions die due to aging. Hundreds of millions of others suffer age-related disease.
Just as for other research prizes, every dollar in the MPrize fund will inspire many more dollars in funding for biomedical anti-aging science from other sources. These first years of the 21st century are as a auspicious time as you will ever see to start the first pebbles of this avalanche. We stand at a tipping point of public support and awareness of a future of extended healthy life spans - and folk like you and I can help to kick-start real, significant progress:
The M Prize has the potential to remove the stumbling blocks preventing scientists in government and industry from taking on the aging process as a curable disease. On the one hand, it reorients the incentives for industry. Right now, there is no specific incentive for private researchers to perform lifespan studies in mice: at most, they are a stepping stone toward long, expensive, human trials - and as noted, even the rodent studies are long and expensive. When a significant financial reward - and the promise of substantial publicity - is put in place, however, suddenly there is a business case for spending a few years rather than a few months in testing a compound in mice. Should you succeed in rejuvenating mice, you can bet that Big Pharma will be beating down your door for the rights to translate the intervention to the human case.
The M Prize can dislodge the vicious circle that drives the lack of serious anti-aging biogerontology in academic research. For the scientists, it creates an incentive to write those grant proposals, in hopes of obtaining more funding directly and greater prestige for their institutions - prestige itself tends to attract more funding. On the side of public opinion, the Prize structure, by its nature, captures public imagination and provides a dramatic way to educate the public and media that scientists are working on extending healthy lifespan in mammals. This increases the credibility of any similar reputable efforts and wins acceptance for the idea that it can be done in humans. In turn, changes in public opinion eases political constraints on awarding public funding for such projects - and may even lead to active pressure to make such awards.
The real tipping point, however, comes when aging is demonstrably reversed in an elderly mouse. Aside from the obvious point that success in mice implies a parallel success in humans with adequate further research, it may initiate a sea change in public opinion as people allow themselves to believe that aging could be cured in humans. I envisage this leading to a public and political demand for a War on Aging. At this point, the whole field of serious anti-aging research will become scientifically respectable. It will attract scientists and funding; this will further fuels the expectations of the public and pressure for public and private funding.
One of us will be the 100th member of The Three Hundred - perhaps it will be you. The future is, after all, in your hands.
LiveScience has up an article on the results of the $20,000 SENS Challenge. It, like the results themselves, is illustrative of confusion as to the nature of the Strategies for Engineered Negligible Senesence (SENS), and what is meant by "science" - confusion that will have to be cleared up at some point in the near future. Given that the first SENS projects aimed at repairing one aspect of age-related cellular damage are presently underway at the hands of scientists - in laboratories, using the scientific method, aiming at publication and peer review, and so forth - I think it's rather hard to say it's not science. Science is a matter of plans, tasks and speculative research as well as what has come before and is, for the moment, proven. SENS is science in the sense of an ongoing - and only partly funded as yet - project plan based upon the best of present day knowledge, not science in the sense of what you find in a textbook. You can find more in this vein in my commentary on the results at Fight Aging!
Via the Technology Review, a short overview of recent research into regenerative medicine for neurodegeneration: "We know new cells are made and go to the site of new injury, whether it's stroke or Parkinson's or Alzheimer's. One strategy to treat neurodegeneration is to boost this response. ... Recent studies have shown that many types of drugs - antidepressants, cholesterol-lowering drugs, even Viagra - spur growth of new neurons in the brain ... scientists can use these compounds to figure out how certain drugs trigger neurogenesis and then try to find or design compounds that boost new cell growth even more effectively ... scientists found that a drug similar to those used to treat Parkinson's disease can spur growth of new neurons in the brain area damaged in the disease. Scientists found that treated animals had twice the number of proliferating neurons as control animals, and that many of the newly generated cells appeared to develop into dopamine neurons. In addition, the animals showed an 80 percent improvement in their motor ability."
The New York Times profiles researcher Anthony Atala: "The field of tissue engineering is large in this endeavor, with researchers like Dr. Atala exploring a basic approach. To repair or replace parts, they seed a biodegradable scaffold with cells and insert it into the body, where the cells, if all goes smoothly, mature into functioning tissue. At the institute, he and more than 80 colleagues are working on tissue replacement projects for practically every body part - blood vessels and nerves, muscles, cartilage and bones, esophagus and trachea, pancreas, kidneys, liver, heart and even uterus. In the long term, the scientists hope, patients may no longer have to wait on the national transplant list 'for someone to die so they can live,' as Dr. Atala puts it. Organs could be tailor-made for people."
Those arriving late to the party may want to visit the SENS website and look at a summary of the background of the SENS Challenge before reading on. This has become a slightly involved story, or at least one that requires more than thirty seconds of reading time.
"We need to remember that all hypotheses go through a stage where one or a small number of investigators believe something and others raise doubts. The conventional wisdom is usually correct. But while most radical ideas are in fact wrong, it is a hallmark of the scientific process that it is fair about considering new propositions; every now and then, radical ideas turn out to be true. Indeed, these exceptions are often the most momentous discoveries in science.
"SENS has many unsupported claims and is certainly not scientifically proven. I personally would be surprised if de Grey is correct in the majority of his claims. However, I don't think Estep et al. have proved that SENS is false; that would require more research. In some cases, SENS makes claims that run parallel to existing research (while being more sensational). Future investigation into those areas will almost certainly illuminate the controversy. Until that time, people like Estep et al. are free to doubt SENS. I share many of those doubts, but it would be overstating the case to assert that Estep et al. have proved their point."
A majority of the judges also argued that if SENS was not exactly science, de Grey (a computer scientist by training) had described his proposals as a kind of engineering project -- and they upbraided Estep et al. for not considering them on those terms. Rodney Brooks wrote, "I have no confidence that they understand engineering, and some of their criticisms are poor criticisms of a legitimate engineering process."
Craig Venter most succinctly expressed the prevailing opinion. He wrote, "Estep et al. in my view have not demonstrated that SENS is unworthy of discussion, but the proponents of SENS have not made a compelling case for it."
You might also want to take a look at my earlier comments on the submissions. I am, it has to be said, surprised that editor Jason Pontin has gone ahead and awarded his half of the $20,000 prize to Estep et al (who will be donating it to the American Federation for Aging Research) despite the judges' opinion. To me, this is a helpful reminder that Pontin, for all he's shown himself to be a stand up fellow, is no supporter of SENS. I get the impression that, after past events, he would like to draw a nice line under this episode, declare victory irrespective of the contents, and move on.
The original terms of the challenge were to demonstrate SENS "so wrong that it was unworthy of learned debate." I think that the judges have demonstrated clearly and sensibly, as one would expect, that this isn't going to happen. SENS is a combination of ethical goals, present day biomedical research, and yet-to-be-funded research and development plans grounded in the science we know today. In that, it is no different from any well-researched scientific and engineering research and development proposal. Rodney Brooks hits it right on the head with his comment.
What we learn from this, as advocates for greater meaningful anti-aging research and development in the near term? What I take away from this is that "science," "engineering," and "plan" mean very different things to different people - even to different scientists, engineers and planners. Some people think that SENS is not science. I say those folk have a strange idea as to what science actually is, given that a number of scientists are presently working on SENS projects. That side of SENS looks very much like science to me: the scientific method, laboratories, biotechnology, fathoming the great unknown, peer review and publication; all very traditional.
How about the other side of SENS, the proposals and suggested courses not yet funded? One could look upon these engineering approaches as the delivery of solutions in the lack of full knowledge of the problem space. Science is there to increase understanding of that space, thus making engineering easier - but you don't need complete knowledge to obtain useful results. People were successfully building bridges long before modern mathematics and materials science, but those tools enabled bigger, better, more durable bridges. There is no bright line between science and engineering in planning, organization and divison of labor: think of the scientific research funded and accomplished in the cause of bringing bridge-building techniques up to a level required for proposed projects of the Brunel era.
The one crucial thing to take away from what biomedical gerontologist Aubrey de Grey proposes in SENS - and many other scientists agree with - is this: we presently know enough to make serious inroads in medical engineering aimed at reversing aging. We can build the first of those bridges - but we are not yet doing so, and each year of delay will cost tens of millions of lives.
UPDATE: The TR staff just added an additional, new response - more in the way of another personal attack - from Estep and company. Aubrey de Grey responds to it in the comments on that page. Come on guys; if you're going to set up a forum for debate, at least stick to the form.
Irresponsibility and lack of accountability built into the structure of modern government leads to the casual, uncaring treading of freedoms underfoot. In this case, the business of cryonics was made illegal in British Columbia, as reported in The Tyee: "when B.C.'s anti-cryonics law came into place, Best doggedly researched the whys and what-fors of the law. ... After contacting many government officials, I discovered that this law was created by one bureaucrat and everyone else just went along with it. I think this guy even forgot he'd done this when I contacted him again 10 years later. So it was a pretty slapdash thing, but once in place, hard to change." And yet people go along with it, making it easier for the next bureaucrat to invade their lives and steal freedoms. Beyond the aspect that caught my libertarian eye, you should find this article to be an informative, respectful look at modern cryonics and its supporters: read it.
"Pay Death to Go Away." A different author could have done so much more with that article seed than this effort at Forbes. It starts promisingly enough:
Nobody wants to die--but what if you could pay the piper with cash, instead of your mortal soul?
People have always been willing to spend money to try to pay off the Grim Reaper. But modern would-be immortals know that old-fashioned cure-alls, like the ground mummy dust to which hopeful aristocrats turned in medieval times, were only so much quackery. And modern medicine has done a great job of extending our lives already. In the past 100 years, the human life span has increased 65%, to 78 years.
Sadly, it misses the point thereafter. An opinion: the most boring, prosaic thing you can do with your wealth is to buy what already exists. Why even strive for wealth if that is all you will do? The only real difference between those who get by and those who have built up deep pockets is that the latter group has far greater leverage to change the world - to buy what does not yet exist.
There is presently no way to pay age-related degeneration and death to go away. A hundred thousand people end years of age-related pain and suffering in death each and every day: they would pay if they could. Calorie restriction is most likely the best available option today to obtain any sort of modest healthy life extension, and taking up that lifestyle choice will almost certainly reduce rather than increase your expenditures.
There is, however, an option that apparently didn't occur to the author of the Forbes article: devoting your resources to plausible longevity research, thereby helping to create medical technologies that will allow people the choice of paying death to go away.
If you have built wealth of any stature, use some of it to fund the medical research that will change the world; you'll benefit far more in the long run.
A PDF of the first chapter of the Handbook of the Biology of Aging is freely available. It discusses the reliability theory of aging and longevity: "Empirical observations on aging have become so abundant that a special four-volume encyclopedia, The Encyclopedia of Aging (1,591 pages), is now required for even partial coverage of the accumulated facts. To transform these numerous and diverse observations into a comprehensive body of knowledge a general theory of species aging and longevity is required. ... A reliability-engineering approach to biological aging is appealing because it provides a common scientific language (general framework) for scientists working in different areas of aging research,
helping to overcome disruptive specialization and allowing researchers to
understand each other. Specifically, reliability theory helps researchers define more clearly what is aging. In reliability theory, aging is defined as a phenomenon of increasing risk of failure with the passage of time (age)."
A great many folk who support healthy life extension research are not actually working towards better medical technologies or increased support for these goals. I'm not just talking about your occupation here, but rather whatever time you give to a cause you believe in - which may or may not include that day job or entrepreneurial effort. This isn't shocking; it's much the same for any given cause, and it's your choice as to where your time is spent.
What interests to me, for the purposes of this post at least, is that a number of activities are seen viable - or even better - in comparison to the direct approach to advancing progress towards longevity-enhancing technologies. For example, research advancing any of the following goals:
- Cellular biochemistry, genetics and other broad modern medical research
- Nanomedicine and dry nanotechnology
- Computational technology
- Bioinformatics development
- Artificial general intelligence (AGI)
Is this a valid way of looking at these activities? Can one be an AGI researcher and claim to be bringing forward the time at which healthy life extension technologies will become widely available?
In the long term, the answer has to be yes. Any infrastructural technology is fair game if it can be related to future medical technologies capable of repairing age-related cellular damage. Better infrastructure that arrives more rapidly should lead to greater progress in all technologies that utilize or build upon that infrastructure. Beyond that, certain goals will remain impossible or economically infeasible until infrastructural capabilities improve. But how long is the long run?
I'm a first things first sort of person; my instinct is that things don't get done unless you're working on them. You're not going to build that house by focusing on setting up a better cement company. It's important to remember that ramping to an effective research and support community for any large goal can take a decade under the best of circumstances. If you spend ten years helping to build an AGI research community, then you haven't spent ten years helping to build a healthy life extension research community. You can't just turn around at the end and immediately apply the benefits of AGI research to progress in healthy life extension; it always takes more time, more time.
I think it's far to say that it usually takes about twenty years to get anything meaningful accomplished in terms of broadly available, mature infrastructures. That's ten years to ramp up to a large development and support base from the initial seeds of ideas and funding, and then a further ten years to refine the results and attain significant commercial availability. The bottlenecks are always people - the time taken to persuade, advocate, negotiate deals, fight regulations, impose regulations, form companies and nonprofits, navigate sequential business cycles of innovation, and so forth.
My bias again: if you want healthy life extension technologies to arrive soon enough to make a large difference to your healthy longevity, then you should spend those twenty years contributing directly to the development of healthy life extension technologies. If you work upon or support only infrastructure - e.g. only gene therapy, only basic aging research, only AGI or better processing devices for bioinformatics - there is no guarantee at the end of the day that your work will soon speed the goal of longer, healthier lives.
The mistake of the past generation of healthy life extension advocates was to build a commercial infrastructure thinking that the technology would come. It would be a terrible thing for the advocates of this generation to spend decades focused on the creation of infrastructure technologies that will speed the development of working anti-aging medicine - but too late to help, because there was no large, well-funded, dedicated research and development community in place to benefit from them.
Ask yourself this: why is cancer research blossoming so rapidly in response to advances in biotechnology and bioinformatics? It is because the research infrastructure existed, ready to go with whatever new tools are available. If there was no cancer research community, little funding, no widespread support and understanding, another decade or two would pass before all that was brought together.
There are enough people and resources in the world to get everything done that needs to be done to enable a future of far longer, healthier lives. Both direct development and all the infrastructure necessary could happen soon enough to help those of us reading this today. As for all forms of human - economic - activity, this isn't a zero-sum game of resource allocation. But in comparison to resources presently devoted to infrastructural technologies that will help speed healthy life extension research in the future, all too little is going towards actual, direct work on healthy life extension research today.
If we want to be known as something other than unfortunate (and dead) members of the last mortal generation, we need to get up and do something about this state of affairs.
EurekAlert! notes progress in manipulating existing repair systems in the body: "we asked, 'What would be the most ideal, natural way of fixing any sort of problem like this?' If you look at nature, the best way is to simply re-grow the tissue. We know that if we take out a piece of the liver, our body has programming to grow it back to how it was ... [scientists] first identified the signals in the rat heart that currently prevent the ability to re-grow damaged heart tissue. The researchers then manipulated those signals so the heart could work to regenerate itself. ... [researchers] investigated myocardial regeneration by initiating heart cell division and replication. They did this by expressing the cell-cycle regulator, a protein called cyclin A2. It is unique in its control at two major transitions of the cell cycle and is the only cyclin that is completely silenced after birth in mice, rats and humans. This approach - using cyclin A2 expression via gene transfer - yielded improved myocardial function."
Brian Alexander, author of "Rapture: How Biotech Became the New Religion", takes a sensible look at the science and use of growth hormone: "Growth hormone stimulates the production of insulin growth factor 1, which, in turn, affects everything from sugar-regulating insulin to sex steroids such as testosterone and estrogen. A chart of these hormone interactions looks like a map of the London Underground drawn by MC Escher. And as with that massive subway, one train at one stop can wreak havoc with the whole system. ... The right word is 'overwhelming.' It is extremely complex. ... Researchers still know little about the influence of supplemental growth hormone on cancer cells, diabetes and other diseases ... Life extension can be achieved in lab animals, and research being conducted on mice and monkeys will probably pay off for humans someday. But so far, [studies] show that restoring growth hormone to old animals actually shortens, not lengthens, their life spans."
Following up on a recent post on human nature and healthy life extension, I thought I'd point out a couple of examples in the media to reinforce my points.
"Contrary to what many in the scientific community have been saying, people are actually much more concerned about the quality of life rather than the length of it," Mr Partridge said.
"There's been a tendency to just assume that of course everyone will be unconditionally interested in living longer, that they'll want it out of selfishness, but that's really not the case."
These are folk deeply concerned about a supposed future frailty, fraught with irrational fears of overpopulation or worried by basic economic misconceptions. Are we really surprised that people who think it'll be terrible to be alive don't really want to be alive? The doomsayers and Malthusians just don't seem to give up, no matter how wrong they're proven with each passing generation. The world is full of people working hard to build a better future; if they fail, it won't be for lack of forethought or effort. It certainly won't help if they - and we - all age, suffer and die because no-one worked to produce the anti-aging technologies that are within our grasp.
Viewing these sorts of articles continues to reinforce just how important it is to do well in our advocacy. A huge pool of support and resources for meaningful anti-aging research awaits untapped, walled off by widespread misconceptions about healthy life extension and life in a world in which age-related frailty and death no longer exist.
"Anyone who claims that they can stop or reverse the aging process is lying to you - even if they're a doctor. It is not currently possible," says S. Jay Olshansky, a demographer at the University of Illinois at Chicago. "Anti-aging medicine is an industry intended to make money for those who are selling these products."
No one knows how many Americans buy remedies like "youth" hormone treatments, megavitamin cocktails, herbal elixirs and the like. But experts say it's a multi-billion dollar industry that's exploding. Longevity clinics, some charging $2,000 a visit, are popping up around the country. Anti-aging entrepreneurs also hawk their wares on television infomercials, in direct mail solicitations and on more than a thousand websites.
The "anti-aging" marketplace is huge because people are buying. Sellers are serving a need loudly declared by the wallets of their customers; people want the benefits of youth for longer; people want to put off age-related degeneration. No-one's arm is being twisted here and there's absolutely nothing wrong with the concepts of running a business and making money. Caveat emptor is the rule of the day, and whatever delusion and fraud is going on is ultimately that of the customers upon themselves. In a world that contains Google, the internet and ready access to physicians, there is no excuse for failing to understanding the basics of your purchases, your health, aging and what can be done about it.
This is not to say that it's ethical to push fraudulent products upon the ignorant and self-deluded - but the proper response is education, awareness and shunning the frauds, not reaching for a flawed solution in regulation.
I did want to comment on Olshansky's last words in this article:
Even if major age-related diseases were magically cured by tomorrow morning, we would still age and suffer frailty from the body's inability to repair damage to the building blocks of life.
It seems to me that it's past the point of reasonable doubt for major age-related diseases to be considered as failure modes resulting from a buildup of unrepaired biochemical and cellular damage. The conditions and the damage are not items in different buckets on the checklist; one is caused by the other. The body is a machine; like all machines it accumulates wear and then breaks down in ways that are individually unpredictable, but can be classified and given names. Just like cars, only much more complex.
The diagram on the front page of the SENS website is illustrative of the differences in thinking examined in the above paragraph.
Instead, the engineering (SENS) strategy is not to interfere with metabolism per se, but to repair or obviate the accumulating damage and thereby indefinitely postpone the age at which it reaches pathogenic levels. This is practical because it avoids both of the problems with the other approaches: it sidesteps our ignorance of metabolism (because it does not attempt to interfere with metabolic processes and their production of side-effects) but also it pre-empts the chaos of pathology (because it repairs the precursors of pathology, rather than addressing the pathology head-on).
The above diagram sums up the SENS philosophy. The strange arrows with flat heads are a notation used in the literature of gene expression and gene regulation, and they mean "inhibits". Thus, geriatrics is the attempt to stop damage from causing pathology; traditional gerontology is the attempt to stop metabolism from causing damage; and the SENS (engineering) approach is periodically to eliminate the damage, so keeping its abundance below the level that causes any pathology.
UCSF Today reports on a presentation given by Cynthia Kenyon: "Kenyon identified the gene daf-2 that codes for hormone receptors that bring insulin and IGF-1, an insulin-like growth factor, into cells. ... Lower levels of these hormones promote cell maintenance and stress resistance. If there is no receptor for the insulin to enter the cell, cells remain in this maintenance phase and age at a slower rate ... By treating worms with a chemical mutagen that damages daf-2, Kenyon found that the worm's life span increased up to six times its normal existence. ... I'm not saying that people will be able to live for 500 years. But my prediction is that these two hormones also affect aging in humans and that therapies can be developed to ward off age-related diseases and provide five to 10 additional healthy years of life." Her prediction is in much the same ballpark as the Longevity Dividend proposals - in line with what one would expect from tinkering with metabolism in the near term.
A result from the Longitudinal Aging Study Amsterdam gives yet another reason to try to avoid chronic inflammation: "The findings of this prospective, population-based study suggest that higher levels of IL-6 and CRP increase the risk of muscle strength loss, whereas higher levels of ACT [alpha1-antichymotrypsin] decrease the risk of muscle strength loss in older men and women." ACT "limits tissue injuries during inflammations, since it is an effective inhibitor of proteolytic enzymes that are released by inflammatory cells." Correlation is not causation - but it's not hard to think up possible ways in which greater age-related cellular damage due to inflammation could lead to loss of muscle strength.
I thought I'd point you to a couple of the items recently posted to the sci.life-extension group. If you're interested in healthy life extension, it pays to dip your toes into the ocean of medical research, gerontology and biotechnology. It's nowhere near as hard as the science-speak makes it out to be; scientists like their long words, but Google is just a click away. An impression of progress and the complexities involved will give you a far better appreciation of just how much work is yet required, as well as the great progress accomplished to date.
Epithelial keratinocyte regeneration has been exemplified as dependent on a population of cellular progenitors that have retained developmental pluripotency, a latent capacity for proliferation and differentiation with a prolonged lifespan. Recent evidence suggests that the cell populations that regulate the development of normal tissues, and which play vital roles in maintaining the overall homeostasis of the tissue, might be the key target population that is essential for malignant cancer development, thus giving rise to the notion of 'cancer stem cells'.
Cancer is presently the big bad bugbear of all age-related conditions: such a varied collection of complicated, age-dependant biochemical failure modes that we might have to fully understand our cells to defeat it. Or maybe not - it's possible that an engineering approach in absence of full information may lead to significant gains in the fight against cancer. It seems likely that many - or even most - cancers depend upon errant stem cells; how fortunate we will all be if the energies poured into stem cell research uncover a means and the knowledge to deal effectively with cancer.
Reduced dietary methionine intake (0.17% methionine, MR) and calorie restriction (CR) prolong lifespan in male Fischer 344 rats. Although the mechanisms are unclear, both regimens feature lower body weight and reductions in adiposity. Reduced fat deposition in CR is linked to preservation of insulin responsiveness in older animals. ... Collectively, the results indicate that MR reduces visceral fat and preserves insulin activity in aging rats independent of energy restriction.
Scientists are working a great deal more on calorie restriction and related research these days. Anything that reduces body fat is good for your long term health and resistance to age-related disease, but there is a way to go yet towards explaining why and how these various strategies work. There's still plenty of hard evidence to support the practice of calorie restriction while you wait.
In the grand scheme of things, however, this is all a poor substitute for much more directed anti-aging research. There's no such thing as useless knowledge in the long term, but it would be nice to see more aggressively funded and direct attempts to ensure we remain alive and healthy to see the long term.
Via Genetic Engineering News, a long release that provides some insight into aims and progress in human embryonic stem cell (hESC) research at Geron. It covers four areas: "(1) GRNOPC1, Oligodendroglial Progenitor Cells for acute spinal cord injury, (2) GRNIC1, Islet Clusters for diabetes, (3) GRNCM1, Cardiomyocytes for myocardial infarction and (4) osteoprogenitor cells for bone fractures and osteoporosis. ... Our most advanced product, GRNOPC1 for acute spinal cord injury, is in multiple IND-enabling studies. Its in vivo mechanism of action includes myelination and trophic support of damaged spinal cord neurons, resulting in significant locomotor recovery of spinal cord injured rodents. As our work progresses with other hESC-derived cell types such as cardiomyocytes, islets, hepatocytes and osteoprogenitor cells, we are hopeful that these cell types will also demonstrate significant, long-term regenerative capacity in animal models, setting the stage for clinical trials in patients."
Canada.com notes the results of a study to published this month: "researchers found that elderly rats on a calorie-restricted diet had the muscle mass and function of much younger rats. ... It's the equivalent of an 80-year-old rat with the muscles of a 20-year-old rat ... From a young age, the rats ate about 40 per cent fewer calories than normal, although their diet was rich in nutrition. ... elderly rodents on [calorie restriction] experienced only a 20 per cent drop in muscle mass and no loss of muscle function. By contrast, rats eating a normal diet lost 50 per cent of their muscle mass and 50 per cent of their muscle function at old age. ... We know (calorie restriction) extends life span. What we've shown is it also maintains muscle function. ... The study suggests restricted-calorie diets preserve the function of mitochondria which provide the body's cells with energy as the animals grow old. The diets appear to help the aging rats rebuild and replace muscle."
As a follow-up to my most recent post on a future of garage biotechnology - a future that could look much like present day open source software development, rife with possibilities; ever more efficient, ever better - you might want to read this rather depressing piece from Wired:
The main factor limiting an amateur biotech community is the immaturity of the technology, according to Drew Endy, a biological engineering professor at MIT. "Even though it's cheap it's extraordinarily difficult," he said. "The technology isn't reliable enough."
And there's another reason.
"People are very comfortable manipulating silicon," said Endy. "A lot of people, to be blunt about it, are not comfortable with taking responsibility for the manipulation of genetics."
Kim Coghill, a spokeswoman for the Biotechnology Industry Organization, was wary of a potential Bill Gates of biotech starting out as an amateur. "I hope he's not doing (something) in his basement without the guidance of the FDA," she said.
All the members of the collective are familiar with the case of Steve Kurtz, a professor and artist who has had to defend himself against accusations of "bio-terrorism" after local police happened upon his amateur home lab in May 2004.
He says his case has had a moderate "chilling effect."
"Amateurs need experts," Kurtz said. "We come to them with ideas and ask them for help. Scientists are (now) a lot more hesitant to get involved."
Imagine where we'd be today if prosecutors and regulators were breathing down the necks of the early computer hobbyists in the 70s. These groups were part of a culture that gave rise to a huge industry and an ongoing empowerment of the common person far greater than any that has come before. Imagine if those people had not been able to obtain basic parts, if no company would sell to them, if innovation in computing had been squashed down to whatever happened within the conceptual boxes of a few large pre-existing companies and university departments. Government employees are not enablers of progress - they are millstones; the glue in the works; the boot on the neck.
As I've said before, of the challenges facing the future of healthy life extension research and the growth of beneficial biotechnology, it is ignorant, misguided, meddling politicians and bureaucrats that worry me the most. At the end of their road of regulation, taxation, hostility to economic and research freedom, and centralized control lies something that looks much like the old Soviet Union - and each step towards that end is a step away from better medicine and longer, healthier lives.
A nice piece on Alcor and cryonics can be found at the East Valley Tribune: "Because of the increase in clientele, Alcor, a nonprofit organization, has recently had to expand the 'patient bay' that now holds 28 [vitrified] bodies and 46 heads. The patients range from a 21-year-old woman who died of a mysterious illness to a 99-year-old man who died of old age. They will remain in longterm storage until the thawing process is perfected and cures are found for old age, cancer and other diseases, Jones said. While the odds of reanimation are questionable, Jones said amazing medical advancements such as cloning and stem cell research are making the possibility of cryonics not so far-fetched. ... Science fiction is becoming science fact on a daily basis. Why is it such a stretch for this to be along that path?"
ScienceDaily reports on a possible biochemical mechanism for the early progression of Alzheimer's disease (AD): "People with AD exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain (the main characteristic of AD). In the earliest stages of Alzheimer's, beta-amyloid peptides are on the rise, especially in the two connected brain regions critical for memory functions - the hippocampus and entorhinal cortex. ... one reason for that early increase of beta-amyloid peptides: an enzyme that breaks down beta-amyloid peptides, also referred to as an insulin-degrading enzyme (IDE), is not active in the brain in the cases at high-risk for developing AD. ... researchers suggest that boosting IDE activity pharmacologically may reverse beta-amyloid peptide accumulation." This may tie in with recent research suggesting Alzheimer's to be a form of diabetes.
The Life Extension Survey (or LESurvey) is another of the outreach projects put together by active volunteers and advocates of the Immortality Institute forums - kudos to them for standing up, getting things done and growing the community. Support for meaningful anti-aging research doesn't just grow on trees, you know!
The LESurvey is one portion of a larger outreach and awareness effort in the MySpace community. Advocates are leveraging the automation and communication features provided by this sort of online space, so as to expose more people to the concepts of healthy life extension and the plausible future of research in that field. The survey is professionally done, and the results to date should provide food for thought. As Michael Anissimov points out:
Gives a good idea of the opinions of the average Myspace user towards life extension. Apparently most Myspace users are Christian, but cautiously supportive of life extension.
Surveys are notoriously fickle, unreliable tools, but I found this interesting: for the question on length of life desired, most people answered "Depends how things go, but I would like to have the choice to live as long as I want." A tremendous well of resources lies out there, waiting for advocates to find the key to tapping it.
If you would like to read more about - or participate in - these efforts to spread awareness of healthy life extension within online communities, you'll find more information in the following discussion threads:
MarketWatch profiles the Buck Institute for Age Research: "Not long ago, inducing the worlds of basic biology of aging, diseases of aging and biotechnology to share ideas was far from the norm, said Gordon Lithgow, an associate professor of molecular mechanisms of aging. ... Fifteen years ago this wasn't on the agenda. No serious biologist would consider pursuing research on aging. ... Aging is perhaps the biggest risk factor for disease in developed countries. We don't know what aging is; we don't know why it causes disease and don't yet know how to intervene. ... No one really understands why we age....but there are a lot of theories." Biomedical gerontologist Aubrey de Grey would argue that scientists may lack a complete characterization of aging, but know more than enough to get on and do something about the root causes of age-related degeneration. Engineering a solution doesn't require complete knowledge - complete knowledge only makes it easier.
From HON News, signs of further progress in generating new T-cells for people with damaged immune systems: "T-cells are one the of the body's main defenses against disease. In this study, researchers demonstrated that it is possible to convert embryonic stem cells into blood-forming stem cells that, in turn, can turn into the helper T-cells. ... The human embryonic stem cells were incubated on mouse bone marrow support cells, which converted the embryonic stem cells into blood-forming cells. These blood-forming cells were then injected into a human thymus gland that had been implanted in a mouse. The thymus gland converted the blood-forming cells into T-cells." It's unclear as to whether this sort of strategy would help the aging immune system - there may be plenty of T-cells, but their programming has become unhelpful.
The new Immortality Institute home page is up and running - a far better reflection of the discussions and activities coordinated within the forums. The Institute has become a watering hole for a well-connected group of younger life scientists, advocates and supporters; these folk stand firmly in support of rapid progress towards the technologies of radical life extension. The new front page shows this well: mainstream scientific publications by members; serious discussions of pressing questions in present day aging research.
As examples of the type of discussion taking place in the Immortality Institute forums, you might want to peruse the following threads:
If someone can offer an explanation other than tumour suppression for why all human cell types express only the absolute minimum quantity of telomerase that is compatible with their lifelong function, I'll start to take the life-extension potential of these reports more seriously. Until then...
I'm rooting for these people, because we need to see more competition in that marketplace. I'm particularly rooting for those who'll provide the fundamental enabling products that unleash the creativity of others -- the bioinformatics tools, the lab-on-a-chip devices, the gene-parsing and analysis software, the low-cost rapid gene-sequencers, the gene synthesizers, the gene-parsing and analysis software, cheaper and smaller protein crystallography systems, etc, etc. But in which area will we first see movement coming from? Which part of the logjam or gordian knot will loosen up first? I'm thinking it's the lab-on-a-chip devices which will create the most movement in the biotech industry.
I having been reading some of the old sci.life-extension discussions and have realized how little progress we have been making in the last ten years. We still have to discuss why relevant science is not being progressed with deserved effort, or wonder why public does not know jack about this field.
This area of research is totally, ridiculously neglected, especially in higher animals. Great question. Should have been systematically asked long ago in the lab, imo. For a start, this is an inspiring experiment in worms.
If you want more of a window into this fascinating, active portion of the healthy life extension community, then support the Institute by joining as a full member:
"Never doubt that a group of people can change the world. Indeed that is all that ever has." - Margaret Mead
We make the future that we will live in: today we are presented with the opportunity to participate in making a future of far healthier, far longer, far better lives. There is no more noble goal in life than to work towards the medical technologies that will create more healthy life for everyone; to work towards the defeat of age-related suffering, frailty and pain.
Good news from EurekAlert! on the topic of tissue engineered cartilage with possible application to repair age-damaged joints: "engineered cartilage tissue can grow and mature when implanted into patients with a knee injury. The novel tissue engineering approach can lead to cartilage regeneration even in knees affected by osteoarthritis. The tissue engineering method used in this study involved isolating cells from healthy cartilage removed during surgery from 23 patients with an average age of 36 years. After growing the cells in culture for 14 days, the researchers seeded them onto [scaffolds] and then implanted them into the injured knees of the study patients. Cartilage regeneration was seen in ten of 23 patients, including in some patients with pre-existing early osteoarthritis of the knee secondary to traumatic injury. Maturation of the implanted, tissue-engineered cartilage was evident as early as 11 months after implantation."
ScienceDaily notes a growing understanding of how to signal and control stem cell healing processes: "The molecule c-kit is the 'switch' that needs to be turned on by the 'SOS signals' sent by the damaged heart. By binding to another molecule called the stem cell factor - much like a lock and key - the 'turned on' c-kit activates the bone marrow cells to migrate to the heart to help stimulate new blood vessel growth. ... mice with defective c-kit bone marrow cells, could not mobilize these cells to race towards the injured site and regenerate the injured heart. ... The study may explain why some patients have mild heart attacks and others develop progressive and potentially fatal congestive heart failure. ... We know that the number of c-kit positive cells decreases with age and that elderly patients don't recover from heart attacks as well as younger patients. The key for the older patients would be to find new ways to restore this particular subset of cells in their bone marrow."
RegeneRx is working on the development of synthetic Thymosin Beta 4 (TB4) therapies to enhance and direct healing: "it consists of 43-amino acid residues and is found in high concentration in blood platelets, wound fluid, white blood cells, and in most other tissues of the body. TB4 is neither a growth factor nor a cytokine. Rather, TB4 is the major actin-regulating molecule in most mammalian cells and plays an important role in the regeneration, remodeling, and healing of injured or damaged tissues. ... TB4 is multi-faceted and involved in a wide variety of biological activities including: regulation of actin, [regrowth of skin], angiogenesis, apoptosis, and anti-inflammation. ... The fact that TB4 influences so many important biological processes may be one reason why the molecule is so highly conserved and remains essentially unchanged throughout evolution."
The pro-death and suffering Canutes continue to shake their fists at the advancing tides of technological progress and societal change. The world is moving past them now, and their zeitgeist is one of deep denial.
Transhumanism is mostly an intellectual game, a fantasy. The technological breakthroughs necessary to create a true post-humanity will almost surely never come.
All of the fantasizing about living forever and morphing into "post-biological units" won't change the hard fact that we are born to die. Far better, then, to embrace our fully human lives than to seek in vain for a post-human future that will never come.
The problem with transhumanism is not merely in the details, or even in the likelihood that many of these technologies will never see the light of day. Indeed, the real problem is that the very urge and desire to eclipse human limitations is an act of defiance grounded in profound ingratitude. At the core of transhumanism is a basic hatred of humanity. The true humanists are those who accept with gratitude the gift of true humanity.
Arrant nonsense, of course. We are within striking distance - likely a couple of decades, given the right levels of funding - of medical technologies capable of significantly extending the healthy human life span by repairing the root causes of age-related degeneration. Turning cancer and Alzheimer's into manageable chronic conditions will happen on the same timescale. All other related science - materials science, nanoscale engineering, bioinformatics, computational capabilities - is speeding up at a great rate. To deny that we will be able to overcome the worst limitations of the human condition is to deny what is right in front of your face, day after day.
Personally, I see the ability to justify and enact almost any degree of cruelty, suffering and death to be a major flaw in the human condition. Those who embrace this flaw are in no position to preach on the topic of humanism. As above: two supposedly intelligent people who, presumably, are generally pleasant to work or live with, desire to sacrifice the lives and health of billions - fifty million each and every year - to make them feel more comfortable in their own views.
Fortunately, neither Smith nor Mohler are in any great position of power, the better to ensure you suffer, decay and die on their schedule. The advance of science and technology will rapidly render their views irrelevant, given freedom of research. Unfortunately, many people in positions of power share their views, and denial can be turned to suppression. In this world of expansive, intrusive government, in which tens of thousands of lives can be lost through uncaring socialization of medicine it is all to easy to envisage a far worse future.
By all means laugh at the foolishness and cruelty of those who advocate your death and suffering, or seek to use the power of the state to enforce suppression and relinquishment of healthy life extension research. But point out their true nature wherever they occur; we don't want to see a future in which these people are taken seriously.
(Via EurekAlert). Drugs will come to be ever more precisely designed and efficient molecules, intended to control - or reprogram - our biochemistry in very specific ways: "c-Jun is an important disease-causing gene. It stands out because we don't see much of it in normal tissue but it is highly expressed in diseased blood vessels, eyes, lungs, joints, and in the gut - in any number of areas involving inflammation and aggressive vascular growth. ... Our experimental drug, Dz13, is like a secret agent that finds its target, c-Jun, within the cell and destroys it. It is a specific, pre-programmed 'molecular assassin'. ... [this] has the potential to treat a diverse range of health problems, from inflammation and cancer through to eye and heart disease." The best drug development is still a hybrid between the old screen-and-test methods and the designs of the future - a great deal of uncertainty about the success of such a drug remains, due to our lack of knowledge of our own biochemistry.
The evolving dynamics of online publishing and information-seeking communities have become quite interesting. In the past few years the traditional print world focus on new, fresh content has come to overwhelmingly dominate the online spaces, thanks to the popularity of sequential publishing models; RSS, blogs, aggregation and default searches orded by date. That said, popular link sites or pseudo-news sites (Slashot, Digg, Metafilter, so forth) can cheerfully buck this trend and point out older content that might be fresh for a given audience. That audience will then respond by reading, reprinting, discussing and linking to the older content for a while. An article at Slate from the past week looks at just this topic:
For obvious reasons, staffers are as interested in the "most" lists as readers, and so on Wednesday (June 28) our copy chief Rachael Larimore sent around e-mail asking if anybody had an idea why a two-year-old piece by tech writer Paul Boutin ("So Tired," July 13, 2004) had cracked the daily top five. ... Josh Levin, Boutin's editor, quickly determined the origin of the story's new popularity: Digg.com, the husky and growing people-powered news aggregator.
Read the article if you'd like an introduction to a little of the mechanics and economics of directing attention on the web these days. Funnily enough, the very same thing happened recently for a two-year-old interview with biomedical gerontologist Aubrey de Grey on the topic of radical life extension - 1,000 years of healthy life extension, to be exact. The Digg audience found this compelling, and I don't blame them; it is pretty damn compelling. As I pointed out yesterday, while the concepts of radical life extension are old hat for transhumanists and other healthy life extension advocates, they remains uncharted territory and new news for the vast majority of people.
So fire up your browser and refresh your memory - there is indeed a plausible argument that we could live to see millennia-long healthy life spans:
I think the first person to live to 1,000 might be 60 already.
Once the biotechnology ball is well and truly rolling, 1,000 years should be well below the average, given sensible predications on the rate of fatal accidents:
An ageless man] who has lived 500 years has a 50% chance of living another 500 years. And should [he] survive that to reach 1000 years of age, he still has a 50% chance of living another 500 years. This is always true: no matter what [his age], he has a 50% chance of surviving another half-life.
We all have opinions on the plausibility of various timescales for the development and deployment of the first meaningful longevity-enhancing medicine - technology capable of adding a couple of healthy decades at a reasonable cost, and able to be widely commercialized. To me at least, it seems that we'll need another ten to twenty years just to persuade and build a research infrastructure and community capable of the task - but the technology is plausible. It just won't come fast enough to save as many people now living as we would want. This is a tragedy that will be counted in hundreds of millions of deaths, only overshadowed by the prospect allowing the ongoing daily toll of 100,000 lives to continue unabated.
People find radical life extension compelling, and rightly so. The mini-wave of interest in this BBC interview was accompanied by a mini-wave of donations and inquiries to the MPrize for anti-aging research and Methuselah Foundation - that is a hopeful sign.
News-Medical.net reports on confirmation of "immortal DNA" in stem cells: "When a cell divides, its DNA is duplicated and each resulting daughter cell inherits one copy of the DNA. Over time, errors arising during the duplication process can lead to mutations and cause cancers. ... A stem cell can produce two different daughter cells when it divides in the body - another stem cell and a specialised cell that will contribute to the tissue. This is called 'asymmetric division' and helps stem cells regulate their numbers and retain their capacity to regenerate tissue throughout the life of an organism. According to the immortal DNA hypothesis, when a stem cell divides, only the specialised cell inherits the imperfect copied DNA. The stem cell retains the original 'immortal' DNA strand." There are many other sources of DNA damage that can affect a stem cell, possibly turning it into a cancer stem cell. The full paper for this research - which outlines thoughts on immortal DNA, stem cells and aging - is freely available at Cancer Research.
(From Cosmos). Damien Broderick, author of The Spike, takes a look at the coming technological singularity and what it will mean for our healthy longevity: "Here's a jolting change greater than anything we've seen so far in history: by the middle of this century it's possible, even probable, that the relentless ageing of our bodies will be halted by advances in biological understanding plus remarkable new medical interventions. However slowly these health improvements start out, they will carry their beneficiaries forward, step-by-step, year after year, to an era where everyone who chooses has the option of rejuvenation and indefinitely extended youth. Until now, as the playwright Tom Stoppard has noted wryly, 'age is a very high price to pay for maturity.' ... Is there any reason why we can't learn the secrets of the egg cells that ensure healthy youngsters, and then apply those lessons to keep all our adult cells, and the tissues they comprise, healthy and youthful?"
Is it effective - in terms of making people pay attention and take action to support research - to speak of the cost of an age-related disease in terms of years? Does this strategy work for aging in general, in support of SENS research, for example? Via WebMD: "in general, people with diabetes have a risk for heart disease (such as heart attack), stroke, and death from any cause similar to someone more than a decade older but without the disease. Those with diabetes tended to be 15 years younger than people without diabetes when they developed risk factors putting them at high risk for heart attacks and strokes. For men with diabetes, the average age for the transition from moderate to high risk was 48. For women it was 54. ... men diagnosed with type 2 diabetes at age 40 die, on average, 11 to 18 years earlier than men without the disease. Women diagnosed at the same age die 14 to 22 years earlier than women without diabetes." Remember that type 2 - age-related - diabetes is largely preventable.
A recent article on life extension aptly illustrates the root cause of tension between anti-aging and aging researchers on the one hand and the "anti-aging" marketplace on the other. The article is typically superficial journalism, skipping seamlessly between what was once said by scientists whose work is no longer relevant, presently active researchers (with no inkling of their faction within the present heated debate over serious attempts to engineer longer, healthier lives), and salesmen from the "anti-aging" marketplace (with no inkling of their faction within the heated debates over legitimacy and fraud in that arena). So in short, a reader who knows absolutely nothing about the science, culture, history and future of healthy life extension will walk away knowing even less of use or accuracy.
I can't imagine any similarly clueless article on cancer research getting past the editors, but sadly this is the typical point of view for anyone unfamiliar with the healthy life extension community. Our cause - the development of serious, working, scientific anti-aging medicine, and widespread public understanding and support - is still at an early stage of growth, for all the past decades of effort (largely misspent effort, I feel). From the distance granted by unfamiliarity and a lack of domain knowledge, propects for a longer, healthier future are as much defined by the short-term business opportunists, frauds, apologists for degenerative aging and wrong-headed scientists as by pro-longevity researchers, activists and advocates backed by good science and others with a a positive, helpful approach to engineering healthy longevity through scientific progress.
This is not good. It makes it harder to present the case for greater research funding, and it hides the useful, rapid paths forward beneath a mountain of junk, slow trails and dead ends, nonsense and opportunistic responses to calls for instant gratification. Harder work means slower progress, which means the yearly toll of tens of millions of lives lost to age-related degeneration will continue that much longer; hundred of millions more will suffer horrors, pain and decay of aging that might have been prevented.
The latest Nature Insight makes for good reading on the topic of stem cell research. It includes a bloglike forum for comments, podcast interviews with scientists, and free access to a number of interesting papers - such as "Stem cells, ageing and the quest for immortality": "There is an overall decline in tissue regenerative potential with age, and the question arises as to whether this is due to the intrinsic ageing of stem cells or, rather, to the impairment of stem-cell function in the aged tissue environment. Unravelling these distinct contributions to the aged phenotype will be critical to the success of any therapeutic application of stem cells in the emerging field of regenerative medicine with respect to tissue injury, degenerative diseases or normal functional declines that accompany ageing."