(From Betterhumans). With the caution that this is only a single study - and much more work needs to be done - psychological stress appears to be linked to shortened telomeres. These protective caps on the end of your chromosomes regulate the normal process of cell death, get shorter with age, and have been implicated as a cause of cancer. While we don't fully understand these mechanisms yet, it seems clear that having shorter telomeres is not a good thing. Chronic psychological stress is already linked with shorter life spans. Understanding why this is the case would be of great benefit, but it's too early to take this particular study at face value - the link to telomeres is tentative and much more work needs to be done.
The New Scientist reports that Austrian scientists have demonstrated a stem cell treatment to regenerates age-weakened bladder muscles. Stem cells were taken from the patients, cultured, and injected into the bladder sphincter. "Within 24 hours, 90% of the women had no urinary leakage. After two weeks, both doctor and patient could a see a marked increase in muscle tissue and contraction power under the ultrasound. Now, more than a later year, 18 of the 20 women have maintained full control over their bladders ... The team is currently treating eight to 10 women per week and long waiting lists are building up." Why is a similar successful treatment for damaged heart muscle taking so long to get past regulation in the US?
I had mentioned that I would link to reports from the last Calorie Restriction Society Conference when it was feasible. Here are links to Dean Pomerleau's rather good entries, with thanks to Michael Rae for the pointer:
Go and take a look - I think you'll find it educational and informative. I'm looking forward to seeing more of the presentation material online as it arrives.
Articles on the well-known difference in longevity between men and women surface every now and again in the mainstream media. I'd found the suggestion that this gender gap stems from the tendency of women to take better care of their health to be fairly compelling, but this research postulates smoking as the root cause:
But Case and Paxson noticed a new trend: Women are losing their edge.
This turned out to be a significant clue in the research on the gender gap. In 1900, women outlived men by a couple of years (48.3 years to men's 46.9), andas longevity increased, so did the gap: By 1970, women lived 7 1/2 years longer than men (74.7 on average compared to men's 67.1).
But then the gap started narrowing. In 2001, women's average life expectancy was 79.8, only 5 1/2 years more than men's 74.4.
Sure, women have always smoked, but they never smoked quite as much as men, Case said. They tended to smoke fewer cigarettes a day, and for fewer years. At age 75, the typical male smoker has 25 years of smoking behind him, while a 75-year-old female smoker has 12 years, half as much cumulative smoking - and half as much damage.
But something changed in the 1960s. The U.S. Surgeon General's report on the health hazards of smoking came out in 1964, and men heeded its warning, Case said. Women didn't.
Men's smoking rates plummeted from almost 50 percent in the early '60s to less than 30 percent by 1995.
Smoking by women, who were undeterred, continued to spiral upward. By the late 1970s, almost a third of women were smoking, up from 20 percent in the 1950s.
Since then, rates have declined slightly, but almost 25 percent of women were still smoking in 1995.
The impact of smoking takes decades to show up. Over the past 20 years, lung cancer deaths for men in their 60s stabilized and then dropped. At the same time, lung cancer rates for women in their 60s climbed steadily, then plateaued.
An interesting theory - and smoking certainly is bad for you. If you're interested in living a longer, healthier life then smoking is a habit you should drop right now. No currently available technology or lifestyle choice can outpace the damage smoking does to your body and life expectancy - and by continuing to smoke you continue to rack up future medical costs above and beyond those required to take advantage of first generation regenerative therapies. It's expensive, and it's killing you.
Betterhumans is printing a very helpful piece on Lifeline and Protandim - a new anti-oxidant regulator with nice lab work from Ceremedix (as CMX-1152) behind it. This article goes in depth on the science and the uncertainty; it's not even entirely clear that what is currently branded as Protandim is the same substance as CMX-1152. While I'm sure that Protandim will be well-received by the healthy life extension community (as was resveratrol), it is simply too early to say whether this pill will have any meaningful benefits. The recent history of supplements is littered with substances that did well in the lab, but do nothing when ingested as pills, or whose supposed benefits were later invalidated. Make your own risk-reward calculation for Protandim, but make it an educated choice.
The LEF News reports that "for the first time, researchers at Stanford University School of Medicine have examined how kidneys change at a molecular level with the passage of time." The findings, from different tissue groups within the kidney, suggest that the same changes in gene activity with age occur in all tissue types. This would certainly be hopeful news if verified - dealing with one type of process will require far less time and research funding than if there were a different process for every tissue type in the body. This "study doesn't suggest what factors drive the aging process, only that once it starts it follows the same path even in different organs ... whatever happens once aging begins, the mechanism that kicks off the process is probably genetically determined."
If you have an eye for long term trends in medicine, you should be watching for progress towards molecular manufacturing and dry nanotechnology. Much of what currently goes on under the heading of nanotechnology in medical and manufacturing industries is simply progress in nanoscale fabrication and application of devices using nanoscale fabrication - good stuff, especially for medical diagnostics, but still a way away from precise molecule-by-molecule mass manufacture.
The level of progress towards dry nanotechnology today determines whether we will see the nanotechnologies of radical life extension arrive in 20 years, 30 years or 50 years. Robert Freitas' respirocytes and other nanorobots form the basis of an entirely new way of thinking about engineering in the human body. There are no theoretical obstacles to building replacements for blood, bone, and even internal cellular components that are hundreds of times more efficient and durable than the biological machinery we currently use - it's just going to be a lot of work.
Nanomedicine will take over enhancing our health and life spans when the gains provided by future regenerative medicine come up short. It's in our interest to see the groundwork for nanotechnology moving ahead as rapidly as possible.
If you'd like to keep track of progress, Responsible Nanotechnology is a good place to start. I may not agree with all of their concerns (or proposed solutions) for the future of technology, but they have their fingers on the pulse and provide good overviews of current trends and advances.
SwissInfo reports that the Swiss voted a strong yes on strictly regulated embryonic stem cell research in a recent national poll. "The new law on stem-cell research won the backing of 66.4 per cent of Swiss voters. In French-speaking western Switzerland the percentage was even higher. Canton Geneva recorded the highest level of support at 84.5 per cent. The new legislation will permit research on stem cells from surplus human embryos under strict conditions. The production of stem cells will be limited to embryos not older than seven days." Unfortunately, therapeutic cloning remains banned - which greatly limits the possibilities open to Swiss researchers in this field.
It's somewhat sad that journalists feel the need to play the "balanced reporting" game for longevity science. This Newsday article presents outrageous minority views - calls for the enforced continuation of mass death, suffering and disease - as though they have equal weight and merit as support for medical research and longer, healthier lives. Meanwhile, to quote aging researcher Richard Miller: "For every $100 [the National Institutes of Health] spends on research in biomedicine, exactly 6 cents are spent on research focusing on the mechanism of aging. If what we do in mice were applied to people, many 100-year-olds would be as vigorous as today's 75-year-olds." We need more support and more research!
We already know that cancer and aging share, effect and stem from many of the same biochemical and cellular processes. Now it appears that there may also be a significant overlap between stem cell repair and cancer mechanisms. "There is growing evidence that stem cells gone awry in their efforts to repair tissue damage could help explain why long-term irritation, such as from alcohol or heartburn, can create a breeding ground for certain cancers. ... If these stem cells are the starting point of some cancers, multiple genetic and other changes may be required to trap the stem cell during chronic irritation, and perhaps many more changes to get the rapid growth of cancer. We need to figure out what those changes might be."
(From InfoAging). This point can never be made too many times: "Obese men and women suffer more commonly from a host of potentially deadly and debilitating conditions than people with more slender builds." Even a little excess weight significantly raises the risk of suffering numerous age-related conditions, but obesity is far worse for your health, finances and life span. "Men [with a body mass index of 35 or higher] were eight times more likely to have diabetes, five times more likely to have high blood pressure or knee replacements, four times more likely to have congestive heart failure and three times more likely to report impotence." If you want to live a longer, healthier life, keeping off the fat has to be fairly high on the priority list.
An important - albeit early stage - advance is noted in passing in this article:
Scientists at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the National Institutes of Health (NIH), have induced human insulin-producing cells of the pancreas to revert to islet precursor cells. These precursor cells are capable of expansion and appear to naturally and efficiently differentiate into clusters of islet-like cells. This work may help to clarify the natural lifecycle of the beta cell and may eventually have applications for diabetes treatment.
These sorts of applications are a natural consequence of understanding leading to control of cellular processes and life cycles. Learning how to revert cells to earlier, less differentiated forms is fairly high on the list of things scientists would like to be able to do. One of the ultimate goals is to create stem cells from any cell in the body, while another is to be able to repair age-related damage inside those newly created stem cells. The net result: a personalized biological repair kit to fix the damage of aging and disease.
Optimism for aging research is on display in the South Bend Tribune. "Aging is really a set of processes. They converge and interact with each other. There is a high level of excitement now with aging research. ... Aging research has come of age. The key finding is that aging is plastic, that it can be manipulated ... There is a lot of interest from (large pharmaceutical companies) that was not there two years ago. ... Current research suggests that aging seems to be governed by interaction between the neurons in the brain and hormones such as insulin ... What we don't know is whether the head is the weak link in aging or (if it) is sort of a master control. The excitement in the field is that these studies offer the possibility of rational therapeutic interventions. It is no longer just philosophical. Now we can get going."
The Korea Times reports that researchers in that country have successfully treated a case of paralysis due to spinal injury with stem cell transplantation from umbilical cord blood. "The stem cell transplantation was performed on Oct. 12 this year and in just three weeks she started to walk with the help of a walker." This is a good example of the sort of first generation therapies - comparatively simple transplants - that are being trialed for a variety of currently incurable conditions. This is particularly poignant given the recent death of paralysed advocate Christopher Reeve. How much sooner could this therapy have come about without political opposition to stem cell research? How many more lives have been lost as politicians try to hold back the advance of medical science?
Those of you who follow telomere research in connection with healthy life extension efforts should find this interesting - recent research that extends our understanding of human telomeres and poses a whole new set of questions:
According to Cech, the findings raise important questions about the regulation of telomerase. When telomeric DNA is buried within POT1, telomerase cannot access the DNA to elongate the telomere. "This is something that could keep the cell from making telomeres all day long," he said. "We think this is one level at which telomerase is regulated." Therefore, he said, an important next step will be to determine the cellular mechanism that switches the telomere to the on state so that elongation can occur.
It turns out that human telomere structure is quite different from that of yeast (that researchers had previously been using as a conceptual model for understanding human cellular mechanisms).
One of the engineering methods required for Aubrey de Grey's proposed methodology of reversing aging is lengthening telomeres, since the gradual shortening of telomere length with age is apparently a mechanism by which cancer becomes more common in older people. (On the other hand, rampant lengthening of telomeres is also a good way for cancer to get going, since telomeres control the normal process of cell senescence and turnover in cell populations within the body). How do we work towards lengthening telomeres throughout the body in a reliable, controlled, safe way? Well, we start by determining how human telomeres are structured - as in the work described in this post.
JSOnline reports on the latest set of US state legislators to float the idea of local public funding for embryonic stem cell research. In this case, they are "proposing a 6% tax on face lifts and other cosmetic procedures to finance $1 billion in stem cell research over 10 years. Illinois Comptroller Dan Hynes wants the so-called 'nip-tuck tax' proposal put on the ballot as a referendum in 2006." The passage of Proposition 71 in California is inspiring debate and funding proposals in a number of other states - most notably New Jersey, Wisconsin and Massachusetts. Illinois legislators recently narrowly rejected a proposal to approve embryonic stem cell research in the state - but it is clear that local debate is still continuing.
Sweden becomes the latest European nation to explicitly permit regulated embryonic stem cell research and the associated technology of therapeutic cloning (or somatic cell nuclear transfer, as it is referred to in this article). "It is hoped that stem cell research will be able to lead to new methods of treatment for serious, currently incurable diseases like Parkinson's disease, diabetes and cardio-vascular diseases. It is also hoped that it will be possible to repair serious tissue damage such as injuries to spinal bone marrow. The objective is to replace dead cells with healthy ones and in this way restore functions that have been lost." Has the tide turned past the point of serious political opposition to this vital field of research? We can certainly hope so.
Michael Rae (of the CR Society) penned an informative post on calorie restriction (CR) research at the Immortality Institute today:
One of the most distinct effects of CR is the lowering of integrated insulin and glucose levels, and it's widely believeed that one or the other or both play major roles in the anti-aging action of CR. To test this, one wants to be able to manipulate one or the other or both, without lowering Caloric intake.
Famed CR and exercise researcher Roger McCarter has been doing some work with transgenic (TG) animals that overexpress the gene for GLUT4, the main glucose transporter in skeletal muscle. Basically, when insulin stimulates muscle, there is a cascade of molecular events which move GLUT4 to the cell surface, where they engulf glucose at the plasma and move it into the cell. By making more GLUT4, these mice suck up more glucose. Somewhat surprisingly, their insulin levels don't go down in homeostatic adjustment: they just have lower circulating glucose levels (and thus, presumably, fewer extracellular [advanced glycation end products]).
One of the many exciting things on which you missed out if you didn't come out to the CR Society 2004 Conference was McCarter's old coinvestigator, Ed Masoro, informing us that McCarter has found that these GLUT4 transgenics have no changes in their lifespan. This suggests that, at a minimum, low glucose levels per se -- and extracellular AGE -- are not the *primary* mechanism of CR's anti-aging action, and may conceivably not contribute to it at all.
Now, in results presented at the 2004 Gerontological Society of America meeting, they report that the lower glucose level does not appear to effect (OR affect!) CR-associated gene expression changes.
The interesting science continues to roll in for calorie restriction - a sign that decoding the puzzle and the ensuing production of CR mimetic therapies for healthy life extension cannot be too many years in the future. In the meanwhile, there's nothing stopping you from investigating calorie restriction the old fashioned way. Why wait years for treatments when you can get started on at least modestly extending your healthy life span right now?
I pointed out an article on life expectancy statistics last week, and said:
What benefits to life span have been incidentally derived from advances in medical technology? I think we're all aware of the underlying reasons for large gains in life expectancy - but comparatively little has been gained in the extension of healthy old age: "In 1900, the average 65-year-old could expect another 12 years of life, on average. A century later, in 2000, life expectancy post-65 had increased to 19 years for women and 16 years for men. Similarly, in 1900, 85-year-old Americans could expect an additional four years of life. By 2000, that statistic increased seven years for women and six years for men." Clearly, incidental life extension only gets us so far - we need more directed research into the untreated mechanisms of aging.
In a private e-mail, Ian Clements elaborates on the figures:
The Forbes article you quote appears to miss the point about increasing longevity. The apparent near-doubling of Western lifespans over a century or so is, to a large extent, a statistical trick, implying the average person now lived twice as long - well, yes, if the average includes the new-born. It was the high death rate of the latter that has dramatically fallen, giving rise to the apparant doubling lifespan. But for an adults, lifespans haven't doubled.
But they have STEADILY increased - and THAT is the point. There is a linear increased lifespan for all adult ages, including the very old, over the recorded couple of centuries we've had figures. This is the basis for maintaining that there is no 'natural' upper limit; if there was, then the increase in lifespans would be levelling off.
So don't let's worry that the increases are small, but note that they are continuously linear (or even increasing). This gives hope that we can uncover the mechanisms which cause steady degeneration, and slow or reverse them.
The Reliability Theory of Aging is a good introduction for newcomers who want to place the historical extension of longevity - and thoughts about limits on life span, or lack thereof - within a scientific framework:
"We are like machines made up of redundant components, many of which are defective right from the start." Machine failure rates and human death rates are very similar in form - which should not be too surprising. Reliability theory predicts no fixed upper limit to life span: "Even small improvements to the processes of early human development - ones that increase the numbers of initially functional elements - could result in ... a significant extension of human life."
Within the framework of Reliability Theory, we can suggest that gains in life expectancy in old age are incidental - they result from reductions in bodily damage due to chronic disease. As advances in medicine eliminate or minimise diseases that plagued our ancestors, we benefit as the complex machines that are our bodies run better, for longer.
It's still past time to get to work on directed research into real anti-aging medicine, however. The incidental rate of increase of healthy life span is far too slow for my liking.
This SignsOnSanDiego article gives a brief look at the way in which the scientific community is divided on the subject of extending healthy life span. "The good news is that most scientists think human life expectancies can be substantially stretched." The public debate taking place today is over how much stretching can take place, and how soon new medical technology can be developed - this debate greatly influences research funding. Personally, I think that the faction represented by S. Jay Olshansky is taking an unreasonable position. The technology and models proposed by Aubrey de Grey for the future of serious anti-aging research are much more plausible - far better to get on and solve the problem of aging than to extrapolate a gloomy prognosis based on historical data on aging!
SignOnSanDiego takes a look at some of the science backing calorie restriction as the only currently available way of even modestly extending healthy human life span. "A human study by John O. Holloszy, a professor of medicine at Washington University in St. Louis, published earlier this year noted that 18 people who had been practicing CR for three to 15 years showed dramatically reduced risk of developing diabetes or clogged arteries.
... It's very clear that calorie restriction has a powerful, protective effect against diseases associated with aging ... We don't know how long each individual actually will end up living, but they certainly have a much longer life expectancy than average because they're most likely not going to die from a heart attack, stroke or diabetes."
Betterhumans gives more background on the research behind the inaugural award of the Methuselah Mouse Rejuvenation Prize. "The research showed conclusively that mice fed a calorie-restricted diet in middle age had fewer age-related diseases and lived longer than mice on normal diets, suggesting that the intervention and drugs that mimic it could provide the same benefits to middle-aged humans. Spindler worked on the project with scientists from Campbell, California-based BioMarker Pharmaceuticals Inc., which is working to develop drugs that reproduce the beneficial effects of caloric restriction." By recognizing and rewarding this sort of early rejuvenation research, the Methuselah Foundation hopes to encourage more and better progress towards healthy life extension in the future.
The Methuselah Foundation is happy to report that they have awarded the first Rejuvenation Prize to Stephen Spindler, who led "the first experiment to achieve rejuvenation in middle-aged mice, making them biologically younger while extending their lifespans." The Methuselah Foundation prize fund is supported by public donations - by people like you and I who wish to make a tangible difference to the future of medicine, health and longevity. Donors include the "X PRIZE Foundation, Foresight Institute, the Life Extension Foundation, Dr. William Haseltine -- Founder of Human Genome Sciences and Dr. Raymond Kurzweil -- noted futurist and entrepreneur." I encourage you all to step up to the plate and make a donation that will help to invigorate serious anti-aging research!
Here's one for the political junkies amongst you. Chris Mooney has penned a host of informative posts on the recent politics of stem cell research conference at Rice University.
Goldstein gave a primer on the field, helpfully explaining why stem cells--and especially embryonic ones--are so medically promising. He noted that these cells could help us get past four major "bottlenecks" in the development of medical therapies: 1) there aren't enough sources of tissue for transplantation at present, but we might grow vast amounts of transplant tissues from stem cells; 2) drugs are very expensive to make because of the cost of human trials and because animal trials can lead scientists down the wrong road, but we might do better by testing drugs in human stem cell preparations; 3) we have an incomplete understanding of disease mechanisms, but research on stem cells with specific disease fingerprints will allow greater understanding of the development of many conditions; 4) we have enormous variation among individuals in terms of their response to various drugs and therapies, but down the road stem cells derived by nuclear transfer (or adult stem cells) could lead to patient-specific therapies.
I thought this "bottlenecks" approach provided a great way of explaining all the different reasons for doing stem cell research. Stem cells are "not a one trick pony," Goldstein explained; rather, the field should be thought of as a "broad enabling technology." Unfortunately, this point is frequently lost in the debate.
Moving on in his presentation, Goldstein talked about the limitations of adult stem cells, so beloved by the religious right. He noted that these cells: 1) are promising but have limited applications, and are poorly understood except in the case of the much-studied hematopoietic stem cells; 2) have restricted potency and growth potential, according to most studies. On the second point, Goldstein added that studies suggesting otherwise have not yet been independently reproduced and tend to suffer from "flawed designs, flawed assays, [and] poor data quality." To top things off, Goldstein concluded that even the scientists who specialize in adult stem cells think embryonic research should go forward as well. You will find "no strong scientific opinion that says you can do one to the exclusion of the other," he said.
Finally, Goldstein talked about Alzheimer's disease. Conservatives have argued that stem cell research has nothing to do with Alzheimer's, but this would come as surprising news to Goldstein. He noted that the disease has two basic forms--hereditary and sporadic (the most common human version)--and that embryonic stem cell research promises to be useful in each case.
For hereditary Alzheimer's, Goldstein explained, we could 1) genetically screen IVF-derived embryos for those that have the condition; 2) derive stem cells from these selected embryos and grow those cells into brain cells; 3) use these brain cells as a screening tool to test for new drugs. For sporadic Alzheimer's, on the other hand, Goldstein noted that the disease has complex origins and cannot be detected simply through genetic screening of embryos. Nevertheless, he continued, scientists might: 1) create cloned embryos containing the DNA of grown adults who have developed this condition; 2) extract stem cells from those embryos and grow them into brain cells; 3) conduct drug testing in these cells. In short, embryonic stem cell research could tell us a lot about Alzheimer's.
Chris Mooney makes the point that this sensible sort of presentation of research, potentials and what it all means doesn't seem to be making it into the mass media. Well, this is a (very) small start.
How does the UK regulate embryo research? Well, all research is approved on a case-by-case basis and those submitting applications have to show that the work is necessary medically, for one thing. No one can use embryos older than 14 days, genetically engineer human embryos, or implant them in wombs. For each line, researchers also have to put a sample in the UK Stem Cell Bank to be shared with other scientists. Britain has also, more recently, allowed "therapeutic cloning" or cloned embryo research to go forward.
First, Battey directly addressed President Bush's August 2001 claim that "more than 60" genetically diverse embryonic stem cell lines existed at the time of his speech. Saying this statement had generated "confusion," Battey blankly noted, "There weren't 60 lines. There were more than 60 derivations." See here for my explanation the crucial distinction between derivations and lines.
As if this isn't outrageous enough, Battey added that back in 2001, there was probably only one well-established embryonic stem cell line. Looking forward, he also noted that, with 22 actual lines currently available, there's only one more line that's well along in development and might be available to researchers at some point in time--leaving the likely final total under the Bush policy at 23.
Attorney Gregory Glover, of the firm Ropes & Gray, took a first crack at this question. He said that there are differing interpretations of the constitution's Commerce Clause and often, the clause's scope ends up being decided on political grounds. I didn't find this particularly useful, but in the question and answer period Glover went further. He noted that should the Brownback bill pass Congress, California could be expected to file an injunction against it, asking for constitutional review. At that point, there would be a legal limbo, allowing research to continue in California until the case is heard. But after that, the state could have to fall in line if the law was deemed constitutional.
In a later session, lawyer and ethicist John Robertson of the University of Texas went further. Without discussing the Commerce Clause, he argued that the Brownback bill would be unconstitutional under the First Amendment, and might also be unconstitutional under the Fifth and Fourteenth at some point in the future. Why? Well, as far as the First Amendment goes, Robertson thinks that banning research would amount to a content-based restriction, which would be an unconstitutional interference with free speech. As far as the Fifth and Fourteenth Amendments go, meanwhile, Robertson thinks that as soon as life-saving therapies from this research are available, it would be unconstitutional to deprive people of "life" and "liberty" by blocking them from getting these treatments.
Ugh. Based on the results of conflict between the states and Federal government over medical and drug policies, I don't see the resulting fight over therapeutic cloning being pretty. This is why it is very important to continue to loudly oppose the pending criminalization of therapeutic cloning in the US.
It has to be said, based on those last three posts, that watching the regulatory impulse in action is distressing. So many people so desperate to exert control that they would damage and destroy valuable progress in medical science rather than see it succeed. The irony is, of course, that the success or failure of any distributed activity (like medical research) is beyond the ability of any politician or regulator to control - all they can do is slow the rate of progress and impose additional costs.
The best thing that all these folks can do is to get out of the way. Real progress requires freedom.
Newswise reports on an advance in tissue engineered blood vessels (TEVs). Blood vessel development is currently a sticking point for the on-demand growth of replacement organs and other complex tissue. Scientists are making progress, however: "We have shown that fibrin-based vessels can be implanted in vivo, remain patent and support blood flow rates for 15 weeks. ... "It's not a stretch to extrapolate that these TEVs could remain functional in the long term because the animals presented no adverse effects .. the TEVs performed like native vessels 15 weeks after implantation ... exhibited excellent "remodeling," producing collagen and elastin, and had increased their mechanical strength by more than a factor of three."
(From the The Scotsman). UK scientists are projecting a 10 to 15 year timeline for curing deafness using regenerative medicine based on embryonic stem cell research. This is much in line with projections for other similar initiatives to treat degenerative conditions using stem cells. "Researchers from Sheffield University are using embryonic stem cells in efforts to grow new cells in the inner ear. ... during the 10 months of research conducted so far it had been shown that stems cells from the sensory nerves could be regrown in the damaged area, potentially leading to the return of hearing." As a general rule, it takes a decade to get from the laboratory to full commercialization - while modern science is getting faster and cheaper, the old regulatory and human costs are staying much the same.
I noticed a nice entry on the tangible economic results of progress in medical science from Randall Parker at FuturePundit:
Charlie Rose conducted a group interview of Robert Klein, campaign chair for the Calfornian Proposition 71 embryonic stem cell funding initiative, Brook Byers, partner at venture capital firm Kleiner Perkins Caufield Byers, and Susan Desmond-Hellman, president of product development for Genentech. The general area of discussion was about biotechnology and medicine. These three interviewees all agreed on one very important point: only innovation can solve the problems caused by high and rising health care costs. It was gratifying to see these figures make an argument that is familar to readers of my blogs. Scientific and technological advances will be the ultimate solutions to the rapidly rising costs of medical care.
In one of his Lives Of A Cell books (this is an old memory, forget which one, probably Lives Of A Cell: Notes Of A Biology Watcher) published some time in the 1970s Thomas noted that before the advent of effective treatments of tuberculosis the many tuberculosis sanitariums were very expensive to operate. But he pointed out that once effective drugs against TB were developed the vast bulk of the sanitariums were quickly shut down as their patients were quickly and cheaply cured of TB. Thomas contended that expensive treatments are expensive because they fail to fix the underlying causes of diseases and that just about any really effective treatment is going to be pretty cheap. I agreed with him then and decades later I've grown only more confident that he correctly saw the fundamental problem (far more important than tort law, regulations, tax law, government entitlements programs, or market failures) that that is the root of high medical costs.
"In my own early professional life when I was an intern on the wards of Boston City Hospital the major threats to human life were tuberculosis, tetanus, syphilis, rheumatic fever, pneumonia, meningitis, polio, septicemia of all sorts. These things worried us then the way cancer, heart disease, and stroke worry us today. The big problems of the 1930s and 1940s have literally vanished."
A few of those diseases have made a come-back of sorts. But all are still problems of much lower orders of magnitude than they were a century ago. But what is most important to note is that when effective treatments were found for them the costs of preventing and treating them became a small fraction of the costs that those diseases previously inflicted on their victims, families of victims, and the rest of society.
All very interesting in the context of some of my previous comments on the projected cost of future healthy life extension medicine:
As medicine improves - and improves faster thanks to the efforts of researchers, educators, businesspeople, advocates and other pro-research folks - we will have access to ever more options for living longer, healthy lives. Those options are unlikely to be free, however, especially in the early years of availability. The cost of any given medical treatment drops as marketplace competition sets in and the technology is improved, but most medical expenses require planning.
There are good reasons for believing that costs will remain much the same for major new medical procedures. Very little of that money actually goes towards technology and materials (no matter what that bill says). Most of it pays for people, time, expertise and organizational overhead. Those items tend to remain more consistant across the years even as the underlying technologies, skills and materials change.
I was discussing getting in at the early part of the curve of cost decline - since most of us won't have any other option (aside from the obvious and rather unpleasant one). Still, the very interesting references in Randall Parker's post point to a future - not too far away - in which no-one worries about heart disease, cancer and stroke. What will medical science focus on in those years? If we're lucky, we'll get much more time and money spent directly on aging and serious anti-aging research.
Yahoo! News reports that Brazilian scientists will begin limited trials in the use of a stem cell therapy to treat stroke damage. "The patient ... lost movement in the right side of her body and could not understand other people or communicate with them. Bone-marrow cells from her body were slowly infused in the middle cerebral artery through a catheter on the fifth day after her stroke. After 17 days she was discharged, having recovered movements, comprehension and some speech, with further improvements reported in the following months." Researchers emphasise that this recovery could be natural, but are optimistic about the prospects of a wider clinical trial.
Betterhumans reports on more progress in discovering and manipulating human stem cells: "Adult muscle holds stem cells that could be used to treat nerve and muscle diseases. ... Until a few years ago, muscle cells were thought to be capable of generating muscle fibers only. ... But more recent studies have pointed to the power of these cells to differentiate into mesenchymal cells." Many parts of the human body are turning out to hold stem cells that can be differentiated into several other types of cell and used to build regenerative therapies. These are still early days for the science of regenerative medicine, however. There is a long, interesting and potentially very beneficial road ahead.
A couple of times a month I receive e-mail from people asking for information and advice about medical advances relating to their specific conditions. The purpose of this entry is to provide a modestly encompassing answer for these sorts of inquiries.
Firstly, I am not a physician. I am merely an observer and advocate for medical research aimed greatly extending healthy longevity. That I report on advances - and potential advances, some of which never materialize - in treating specific age-related conditions is par for the course. It doesn't give me any particular expertise beyond a fair general knowledge regarding the current state of research in a few broad fields. I am certainly not infallible, and most certainly not a replacement for your own research, due diligence, decision-making process and responsibility for your own health. You should read the disclaimer here before proceeding.
So, that said, how does one find out more about the current state of play regarding therapies for a specific condition? The first place to start is with your physician or specialist: it is your responsibility to use these folks as a resource for obtaining information about current therapies, what is in the pipeline and access to trials. If you don't ask, you don't find out - so ask!
Specialists in a given field tend to be more aware of the latest work and possibility of placement in clinical trials for new technologies, but they also tend to be behind the curve - as would you if you had a specialist's workload. You have far more time than your specialist to devote to learning about the latest research related to your condition. Knowing how to effectively search the internet and filter out bad information is an essential skill if you want to fully participate in ensuring your own health.
A good starting point - especially for more common conditions - is Google News. Enter the common name of your condition along with terms such as "research," "science" or "stem cell" and see what crops up. In general, the sources used by Google News lean towards the more reputable for this sort of information - press release reprint sites like ScienceDaily and major news organizations like Reuters. This doesn't make these sources infallible (and Google News will only dig up articles from the past couple of months) but it does tend to exclude the more unreliable regions of the internet.
Still, always check the source of a given article! Is it from the newsdesk of a reliable organization, a well-known company, or a press release from a reputable research group or university?
UPDATE 08/22/2005: You might want to read a PLoS Medicine article on how to use search engines to find efficiently find medical information online. It's aimed at beginners, but has plenty of useful pointers and references for more experienced folks. I think you'll find it helpful.
For the purposes of this discussion, I am assuming that if you can read, evaluate (within the broader context of scientific debate in a given field) and extract value from scientific papers, then you already have access to and know how to use sites like PubMed. The majority of us should leave that for the professionals - medical research is still a field in which arguments can take decades to resolve one way or another, generating papers along the way that express every possible point of view. A single scientific paper is not as useful as a single media article - unless that media article is simply parroting the contents of a single paper, but that isn't too common.
UPDATE: Michael Rae opines:
I actually think it's extremely common. A single article comes out in the press, and the story summarizes it in popular form, often with interviews coming only from the investigators -- and in much less cautious terms, and with less review of previous research. When one gets an article with a broader focus, it's often so vague (space constraints, attention span of readership) as to give few to no useful details that a person already asking these questions wouldn't already know. A PubMed search is exactly likely to give one a range of views on a subject, because you *don't* get a single article, but a range of editorial, review, clinical, and preclinical material on the subject (unless one constructs one's search very narrowly -- in which case, one is probably already one o' them professionals ;) ).
What to look for in articles about medical research into your condition? Well, you might consider keeping notes on the following items:
- Which researchers are working on this condition?
- Which research institutions are working on this condition?
- Have clinical trials in humans taken place? Are they working with animals only, or are they still at the stage of tests in petri dishes?
- How successful are results to date?
News articles from responsible organizations almost always list the scientists and research institutions involved.
At this point, I'll assume that if you are interested in researching progress with respect to a given condition, you are probably also interested in find out how to gain access to clinical trials. Human trials take place at all stages through the research and commercialization of a new therapy, and the therapies vary from extremely speculative through to fairly sure things - depending on how far along and how large the trials are. It is important to recognize that all trials can expose the participants to serious risks and that simply having the relevant condition is no guarantee of participation. This is another of those risk-reward calculations that you and your physician or specialist should make in the full knowledge of your own medical history.
But onwards: how does one get into a human trial for a new therapy? The first step is to find out whether trials are taking place, and if so who to talk to about participation. As always, start by talking to your specialist; a well-connected physician is a good thing, but only if they know that you are interested in trial participation.
Beyond that, the best way forward is to pick up the phone and start calling. Take that list of names and institutions you obtained from online research and start working your way through them. Finding contact information for scientists is usually easy - it will be listed on the research institution website, or you can call the department secretary (or equivalent) to obtain it. The research community associated with any given combination of therapy and condition is usually small enough that any given researcher knows who is doing what - and who you should call next. If you are polite and persistent, you should be able to find out everything you need to know about current and forthcoming human trials and who to talk to about participation.
UPDATE: Michael Rae offers the following suggestion:
You might mention http://www.clinicaltrials.gov/, which lets you search initiating, ongoing, and just-concluded-but-unpublished clinical trials registered with the NIH -- a very useful resource if someone actually wants to get involved with same.
UPDATE 09/22/2005: The International Federation of Pharmaceutical Manufacturers and Associations has recently launched a clinical trials site. You should find this helpful as well.
If you find a clinical trial you are qualified for and would like to participate in, involve your physician or specialist in this process. He or she knows your medical history and can help quantify the risks involved. Make your decisions with your eyes open and in possession of all the facts.
Science Daily reports on successful efforts to grow cartilage outside the body - in this case using biodegradable scaffolds and "an innovative bioreactor, which creates mechanical stimulation that builds the tissue." Growing replacement cartilage is a good step forward because "the regenerative ability of cartilage tissue in cases of damage or wear is very limited and nearly non-existent in adults." Age-related joint damage is a big health problem in and of itself, but it also tends to compound other health issues by restricting physical activity. This is one of the many areas in which regenerative medicine can help mitigate the damage of aging.
With the prospect of a UN treaty banning therapeutic cloning now fading, eyes turn to the pending criminalization of this vital technology in the US. Newswise presents some cogent thoughts: "Republican Senators could be voting on acceptable ways to mend a broken heart. I am not referring to reaching out to disappointed Democrats, but rather to the debate on whether the U.S. government should ban embryonic stem-cell research, and its ultimate application in medicine - therapeutic cloning. As they consider the issue, I hope that everyone will weigh the words I recently saw carved in marble on the Thomas Jefferson memorial: 'I have sworn upon the altar of God eternal hostility against every form of tyranny over the mind of man.'"
Lifeline has surfaced again with news about their forthcoming antioxidant-promoting drug, now called Protandim.
Protandim is not an antioxidant, but its patent-pending formulation induces the body to produce more of its own natural antioxidant enzymes, thereby utilizing biology not chemistry to fight oxidation.
The body's primary antioxidant is Superoxide Dismutase (SOD) and its levels have previously been shown to be directly correlated to aging in 14 different species, including humans. Species with the highest amounts of SOD live the longest and any increase in SOD corresponds to an increase in lifespan. According to separate studies conducted by John Tower, a molecular biologist at the University of Southern California, and by molecular biologist John Phillips of the University of Guelph in Ontario, the extended time of life was youth. Old age was postponed.
After very promising pre-clinical results, Protandim is currently undergoing human trials at the renowned Webb-Waring Institute of Cancer, Aging and Antioxidant Research (Webb-Waring). Although the duration of the studies will continue for a period that extends past the projected product release timeframe, there is already enough data to demonstrate the safety and efficacy of the Protandim product.
I imagine that this will prove popular with the healthy life extension community, just like resveratrol, and for all the same reasons. There is a school of thought that suggests trying anything with modest scientific backing for positive effects on healthy life span - and very good backing for a lack of negative effects - is worth the money. This is more of the same risk-reward evaluation that responsible consumers should apply to any supplement or medical product.
I confess that I'm not quite following the shuffle of companies involved in this product, but I'll be interested to see the results from human trials. Like other substances (such as resveratrol), it has some nice lab work behind it to date. The big question, as for all supplements with nice lab work behind them, is whether or not it works once stuffed into a pill...
UPDATE: It's actually rather unclear as to whether the product being pushed by Lifeline is the same as the original (produced by Ceremedix) back when they started out. The same applies to whatever they are testing now - is it in fact backed up by clinical studies, or do those refer to a different chemical or protein? Read this thread from the Immortality Institute forums for more background information.
UPDATE (June 03 2005): In light of all the recent interest, visitors might find it helpful to read my latest post on the topic of Lifeline and Protandim.
RedNova reports on one part of the slow expansion of aging research in larger institutions - the opening of a new biogerontology laboratory at Newcastle University in the UK. "Better understanding of ageing is essential if we are to address the challenges of age-related disability and disease and improve the quality of life for older people. Our research focuses on the mechanisms of ageing and why damage to key molecules such as DNA and proteins leads to chronic disorders in later life." Knowledge is power in medical research - the more we have, the better our lives will be. Newcastle Institute for Ageing and Health researchers have already made important contributions to our understanding of the aging process; we hope to see more of that in the future.
What benefits to life span have been incidentally derived from advances in medical technology? I think we're all aware of the underlying reasons for large gains in life expectancy - but comparatively little has been gained in the extension of healthy old age: "In 1900, the average 65-year-old could expect another 12 years of life, on average. A century later, in 2000, life expectancy post-65 had increased to 19 years for women and 16 years for men. Similarly, in 1900, 85-year-old Americans could expect an additional four years of life. By 2000, that statistic increased seven years for women and six years for men." Clearly, incidental life extension only gets us so far - we need more directed research into the untreated mechanisms of aging.
I've brought up the therapeutic cloning debate at the United Nations many times over the past few months - because I think it is important. A treaty may not have had much in the way of direct legal effects, but it would have been a blow for the fight for freedom of research in many countries. Therapeutic cloning is a fundamentally important technology, vital to much of the most promising research into regenerative medicine and therapies for age-related conditions. Ban it and you throw away the best and most promising stem cell research.
Today, it looks like attempts to craft a treaty to ban therapeutic cloning have been abandoned:
In a victory for advocates of stem cell research, U.N. diplomats on Thursday gave up trying to craft a treaty to outlaw human cloning, and will probably settle for a less powerful document that won't seek a worldwide ban, officials said.
In the end, both sides realized they wouldn't get enough support for a treaty to achieve worldwide ratification, said Marc Pecsteen, a Belgian diplomat in the thick of the talks. Instead, they were leaning toward a nonbinding declaration that would include language ambiguous enough to please both sides.
"There is such a division in the international community that any treaty would not make it. So the idea of the declaration is to find some general language that we could all live with," Pecsteen said.
This last quote sounds like a face saving exercise that will, hopefully, have little effect on research in the US and elsewhere.
Overall, I think we can hope that the tide of public support, funding and actual scientific progress has turned past the point at which politicians are willing to play Canute. In just the past few days, Geron has been loudly proclaiming their embryonic stem cell research results (and more here), while Wisconsin politicians are the latest group of elected officials in the US to declare major funding plans for embryonic stem cell research. I suspect it will be much harder for anti-research groups in the US to push through the pending bill criminalizing therapeutic cloning than in previous years - and a good thing too. Now if that obnoxious bill could just be buried completely, so that it stops scaring away private funding...
Geron has been rolling out tangible results for human embryonic stem cell work of late - a good thing given the current anti-research political atmosphere. The closer science is to cures, the harder it will be for politicians to be shut down or ban research. This latest Geron press release describes progress towards regenerative medicine for diabetes: "Insulin-producing cells can be differentiated from human embryonic stem cells (hESCs). ... Differentiation of pancreatic islet cells from embryonic stem cells is very challenging and protocols reported from work with mouse embryonic stem cells have not proven useful for human embryonic stem cells. We are focused on improving the yield and purity of hESC-derived islet cells to advance our preclinical studies in models of diabetes."
Wired reports that Proposition 71 funding in California is continuing to have effects elsewhere - Wisconsin in this case. "Gov. Jim Doyle announced plans Wednesday to invest nearly $750 million to support human embryonic stem cell research and other medical experiments. The governor wants to use a combination of public and private money to build two research centers and support scientists studying infectious disorders, cardiovascular illnesses and Alzheimer's disease." Much of this proposal is speculative (subject to private backing and a vote in the state legislature), but it shows that organizations elsewhere in the US are concerned about a brain drain to California. Competition is a good thing, even in the realm of government funding, it seems.
The results of separate research into telomeres, human embryonic stem cells (hESCs) and related cellular mechanisms are starting to cross paths again. This is a good sign of progress - it shows that scientists understand these areas well enough to produce applications. In a press release from last week, Geron reports that they can use telomerase and limited control over embryonic stem cell differentiation to produce an immortalized growth medium from the stem cells under study:
In a report published in the November issue of the journal Stem Cells, scientists from Geron and the Roslin Institute demonstrated (i) that fibroblast-like cells could be differentiated from hESCs, (ii) that those cells could be immortalized with telomerase, and (iii) that the immortalized cells could then be used to produce conditioned medium to support feeder-free growth of undifferentiated hESCs.
hESCs are unique, unspecialized stem cells that can be grown in large quantities and differentiated into a wide variety of cell types potentially useful for treating a range of human diseases. Undifferentiated hESCs have unlimited proliferative capacity because they express the enzyme telomerase. In the course of differentiation, telomerase is down-regulated and the resulting differentiated cells have a finite lifespan. In these studies, the researchers derived fibroblast-like cells, termed HEF1 cells, from hESCs. The telomerase-negative HEF1 cells underwent senescence after approximately ten population doublings. Upon insertion of the gene encoding the catalytic subunit of telomerase in the HEF1 cells, the cells stably expressed high levels of telomerase activity, showed continuous growth in culture, and did not senesce. Moreover, the telomerase-immortalized HEF1 cells still responded to osteogenic inductive factors and were capable of differentiating into fully mature osteoblasts (bone-producing cells). These results show that cells derived from hESCs can be immortalized by insertion of the telomerase gene without affecting their ability to further differentiate into functional effector cells.
Geron has previously reported its development of an improved method for culturing hESCs in medium conditioned by mouse embryonic fibroblasts (MEFs), instead of on feeder layers of MEFs, thereby eliminating the need for direct contact with mouse cells. In the new studies, the telomerase-immortalized HEF1 cells were used to produce conditioned medium, which was shown to be capable of supporting the growth of undifferentiated hESCs, including the same hESC line from which the HEF1 cell was derived. The culture system was thus both human- rather than mouse-based, and genotypically homogeneous.
A little technical perhaps - but this is a noteworthy advance in the technologies that support cutting edge research into regenerative medicine. One of the show-stopping problems with many existing stem cell lines is that they are supported on mouse cells. This new advance will make the process of generating stem cell lines to order - in other words, tailored for work on a specific disease - that much easier.
In addition, this lends ammunition to calls for further research into the application of telomerase to extending the working life span of cell groups. You may recall that researchers recently did just this for immune system cells to prevent premature aging in HIV-positive patients.
"Immune cells that fight HIV are under constant strain to divide ... This massive amount of division shortens these cells' telomeres prematurely. So the telomeres of a 40-year-old person infected with HIV resemble those of a healthy 90-year-old person." This sort of premature aging is the result of a part of your body running at an accelerated rate - but with telomerase, "immune cells could divide endlessly. They grew at a normal rate and didn't show any chromosomal abnormalities that might lead to cancer."
So what else can we safely use telomerase for? This would seem to be a question worth spending time and money on.
(From Reason Online). Ronald Bailey weighs in on the current attempts to ban therapeutic cloning at the UN. This piece provides good context and background for those arriving late to the debate. Therapeutic cloning produces "embryonic stem cells that are virtually genetically identical to those of the person who donated the adult cell's nucleus. This means that tissues and cells produced using them would not be rejected by the donor's immune system, and thus would make perfect transplants for the donor." A swathe of the most important research into regenerative medicine and cures for age-related conditions depends on this technology. A UN ban would lend support to those groups attempting to force a ban in the US.
Jump in and read the latest Longevity Meme article, composed of excerpts taken from Fantastic Voyage by Ray Kurzweil and Terry Grossman. While I may not agree with all of the book's focus, I think that the authors do a good job of articulating an expansive, ambitious, but ultimately sensible agenda for the future of healthy life extension and related medical research. This path to the future is often taken as read (and for granted) within the healthy life extension community - but we can never say these things too loudly or too often! Education for the purpose of generating public support for serious anti-aging research is vital to our future health and longevity. It's that view that I hope I've captured with this article.
Read about the vision that Ray Kurzweil and Terry Grossman have for the future of healthy life extension, reprinted with permission from their new book, Fantastic Voyage: Live Long Enough to Live Forever.
Copyright © Ray Kurzweil and Terry Grossman.
Immortality is Within Our Grasp
Do we have the knowledge and the tools today to live forever? If all science and technology development suddenly stopped, the answer would have to be no. We do have the means to dramatically slow disease and the aging process far more than most people realize, but we do not yet have all the techniques we need to indefinitely extend human life. However, it is clear that far from halting, the pace of scientific and technological discovery is accelerating.
According to models that Ray has created, our paradigm-shift rate - the rate of technical progress - is doubling every decade, and the capability (price performance, capacity, and speed) of specific information technologies is doubling each year. So the answer to our question is actually a definitive yes - the knowledge exists, if aggressively applied, for you to slow aging and disease processes to such a degree that you can be in good health and good spirits when the more radical life-extending and life-enhancing technologies become available over the next couple of decades.
Longevity expert and gerontologist Aubrey de Grey uses the metaphor of maintaining a house to explain this key concept. How long does a house last? The answer obviously depends on how well you take care of it. If you do nothing, the roof will spring a leak before long, water and the elements will invade, and eventually the house will disintegrate. But if you proactively take care of the structure, repair all damage, confront all dangers, and rebuild or renovate parts from time to time using new materials and technologies, the life of the house can essentially be extended without limit.
The same holds true for our bodies and brains. The only difference is that while we fully understand the methods underlying the maintenance of a house, we do not yet fully understand all of the biological principles of life. But with our rapidly increasing comprehension of the human genome, the proteins expressed by the genome (proteome), and the biochemical processes and pathways of our metabolism, we are quickly gaining that knowledge. We are beginning to understand aging, not as a single inexorable progression but as a group of related biological processes. Strategies for reversing each of these aging progressions using different combinations of biotechnology techniques are emerging. Many scientists, including the authors of this book, believe that we will have the means to stop and even reverse aging within the next two decades. In the meanwhile, we can slow each aging process to a crawl using the methods outlined in Fantastic Voyage.
In this way, the goal of extending longevity can be taken in three steps, or Bridges. Fantastic Voyage is intended to serve as a guide to living long enough in good health and spirits - Bridge One - to take advantage of the full development of the biotechnology revolution - Bridge Two. This, in turn, will lead to the nanotechnology-AI (artificial intelligence) revolution - Bridge Three - which has the potential to allow us to live indefinitely.
This, then, is the premise of Fantastic Voyage and the case we will make throughout: the knowledge of how to maintain our biological "house" and extend its longevity and vitality without limit is close at hand. We will tell you how to use the extensive knowledge that we do have today to remain heathy as the reverse engineering (decoding and understanding the principle methods) of our biology proceeds.
The 21st Century is Worth Living to Experience
Most of our conceptions of human life in the 21st century will be turned on their head. Not the least of these is the expectation expressed in the adage about the inevitability of death and taxes. We'll leave the issue of taxes to another book, but belief in the inevitability of death and how the perspective will soon change is very much the primary theme of Fantastic Voyage. As we succeed in understanding the genome and the proteome, many dramatic advances in treating disease and even reversing aging will emerge. The first two decades of the 21st century will be a golden era of biotechnology.
Many experts believe that within a decade we will be adding more than a year to human life expectancy every year. At that point, with each passing year, your remaining life expectency will move further into the future. (Aubrey de Grey believes that we will successfully stop aging in mice - who share 99 percent of our genetic code - within 10 years, and that human therapies to halt and reverse aging will follow 5 to 10 years after that.) A small minority of older boomers will make it past this impending critical threshold. You can be among them. The authors of Fantastic Voyage are of this generation and are intent on living through this threshold era in good health and spirits. Unfortunately, most of our fellow baby boomers remain oblivious to the hidden degenerative processes inside their bodies and will die unnecessarily young.
As interesting as the first two decades of this century are likely to be, subsequent decades should lead to even more dramatic changes. Ray has spent several decades studying and modeling technology trends and their impact on society. Perhaps his most profound observation is that the rate of change is itself accelerating. This means that the past is not a reliable guide to the future. The 20th century was not 100 years of progress at today's rate but, rather, was equivalent to about 20 years, because we've been speeding up to current rates of change. And we'll make another 20 years of progress at today's rate, equivalent to that of the entire 20th century, in the next 14 years. And then we'll do it again in just 7 years. Because of this exponential growth, the 21st century will equal 20,000 years of progress at today's rate of progress - 1,000 times greater than what we witnessed in the 20th century, which itself was no slouch for change.
The result will be profound changes in every facet of our lives, from our health and longevity to our economy and society, even our concepts of who we are and what it means to be human. Within a couple of decades we will have the knowledge to revitalize our health, expand our experiences - such as full-immersion virtual reality incorporating all of the senses, augmented reality, and enhanced human intelligence and capability - and expand our horizons.
As we peer even further into the 21st century, nanotechnology will enable us to rebuild and extend our bodies and brains and create virtually any product from mere information, resulting in remarkable gains in prosperity. We will develop means to vastly expand our physical and mental capabilities by directly interfacing our biological systems with human-created technology.
Although human ability to take command of the course of life and death is controversial, we belive that the ability to broaden our horizons is a unique and desirable attribute of our species. And we certainly believe that it is worth the effort to remain healthy and vital today to experience this remarkable century ahead.
Who Is The Enemy?
It is wise to consider the process of reversing and overcoming the dangerous progression of disease as a war. As in any war, if the enemy is at the gates - or worse, inside the gates - it's important to mobilize all the means of intelligence and weaponary that can be harnessed. That's why we'll advocate that key dangers be attacked on multiple fronts. For example, we'll discuss 10 approaches that should be practiced concurrently for preventing heart disease, particularly for people with elevated risk factors.
But if fighting disease and extending longevity and vitality is a war, who is the enemy? At the top of our list we should put ourselves. Of course, health issues get our attention the moment clinical disease strikes, but most people fail to focus on prevention and health enhancement in a timely manner before the onset of overt symptoms. Unfortunately, the medial profession is oriented toward detecting and treating these conditions only after they reach the point of crisis (symptom-control medicine), so most people receive limited guidance on disease prevention from their health professionals. You should not wait for others to show you the path to healing; the only person who can take responsibility for your health is you.
Our second enemy is the disease process itself. Our bodies evolved when it was not beneficial to the survival of the species for people to live beyond their child-rearing years and compete for the tribe's or community's limited food and other resources. Only a century and half ago, life expectancy was 37 years. If we want to remain vital for as long as possible, we cannot simply rely on the natural order that biological evolution has given us.
The third enemy is an increasingly vocal body of opinion that opposes extending human longevity on the basis that it supposedly violates the essence of human nature. Author Francis Fukuyama, for example, considers research that might extend human longevity beyond its current fourscore years to be immoral. Opposition to certain biological technologies such as stem cell research is delaying vital therapies for a wide range of diseases. We should note that we don't consider these thinkers themselves to be our adversaries but, rather, their regressive ideas. The essence of the human species is to extend and expand our boundaries. Ultimately, such opposition will end up being mere stones in a torrent of innovation, with the continue flow of progress passing around these barriers. But even minor delays will result in the suffering and death of millions of people.
Bridge Two: The Biotechnology Revolution
As we learn how information is transformed in biological processes, many strategies are emerging for overcoming disease and aging processes. We'll review some of the more promising approaches and further examples in Fantastic Voyage. One powerful approach is to start with biology's information backbone: the genome. With gene technologies, we're now on the verge of being able to control how genes express themselves. Ultimately, we will actually be able to change the genes themselves.
We are already deploying gene technologies in other species. Using a method called recombinant technology, which is being used commercially to provide many new pharmaceutical drugs, the genes of organisms ranging from bacteria to famyard animals are being modified to produce the proteins we need to combat human diseases.
Another important line of attach is to regrow our cells, tissues, and even whole organs, and introduce them into our bodies without sugery. One major benefit of this therapeutic cloning technique is that we will be able to create these new tissues from versions of our cells that have been made younger - the emerging field of rejuvenative medicine.
As we are learning about the information processes underlying biology, we are devising ways of mastering them to overcome disease and aging and extend human potential. Drug discovery was once a matter of finding substances that produced some beneficial effect without excessive side effects. This process was similar to early humans' tool discovery, which was limited to simply finding rocks and natural implements that could be used for helpful purposes. Now that we can design drugs to carry out precise missions at the molecular level, we are in a position to overcome age-old afflictions. The scope and scale of these efforts is vast; the examples in Fantastic Voyage are only a small sampling of the most promising ideas.
Reversing Human Aging
Our understanding of the principal components of human aging is growing rapidly. Strategies have been identified to halt and reverse each of the aging processes. Perhaps the most energetic and insightful advocate of stopping the aging process is Aubrey de Grey, a scientist with the department of genetics at Cambridge University. De Grey describes his goal as "engineered negligible senescence" - stopping us from becoming more frail and disease-prone as we get older.
According to de Grey, "All the core knowledge needed to develop engineered negligible senescence is already in our possession - it mainly just needs to be pieced together." He believes we'll demonstrate "robustly rejuvenated" mice - mice that are functionally younger than before being treated, and with the life extension to prove it - within 10 years, and points out that this demonstration will have a dramatic effect on public opinion. Showing that we can reverse the aging process in an animal that shares 99 percent of our genes will profoundly transform the common wisdom that aging and death are inevitable. Once demonstrated in an animal, robust rejuvenation in humans is likely to take an additional 5 to 10 years, but the advent of rejuvenated mice will create enormous competitive pressure to translate these results into human therapies.
Earlier in the evolution of our species (and precursors to our species), survival was not aided - in deed, it would have been hurt - by individuals living long past their child-rearing years. As a result, genes that supported significant life extension were selected against. In our modern era of abundance, all generations can contribute to the ongoing expansion of human knowledge. "Our life expectancy will be in the region on 5,000 years ... by the year 2100," says de Grey. By following the three bridges described in Fantastic Voyage, you should be able to reach the year 2100, and then, according to de Grey, extend your longevity indefinitely.
The title of this post is a rhetorical question for many of the readers here. Rainbough Phillips hits most of the necessary points related to this topic in a recent post on healthy life extension:
I take the somewhat Heinlein-ian approach that one who learns to live well can live well indefinitely, and that if one can live well indefinitely then there is no reason why they shouldn't.
I actually came to realize that a far stronger and more reliable impetus for learning and self improvement came from my own desire for growth, and that what I lacked was the belief in myself that I would carry out on that desire without some external pressure to do so.
I think the sentiment that life would be meaningless without death arises from a similar fear. Many individuals think that their friends, neighbors, loved ones, and even their selves will not rise to the occasion and make their lives meaningful and worth living without the certainty of death knocking on the door - as if our natural state is to drift towards a drone-like stupor and only the occasional midlife crisis can knock us out of it. Perhaps this is true for some, but it is not true for all, and I look instead at the valuable amount of time and resources devoted to death.
Without senescence (or rather with negligible senescence) we could save literally billions of dollars per year that is spent on fighting diseases brought on by old-age (various cancers, most type-2 diabetes, osteoporosis etc.).
We could curtail the extremely high prices of funerals, and funerary rituals - when your funeral is a ritual you choose to take on and plan rather than a cost foisted upon a grieving family that simply wants to get it over with, the entire market structure of the industry would change.
We could get rid of the billion dollar industry that sells snake-oil cures to curtail aging. From the makeup that promise to hide "fine lines and wrinkles" to the spa treatments designed to make you look 20 years younger, when senescence is a treatable illness treated by medical professionals instead of a private obsession and a daily gamble on the health and beauty isle, we'll be able to spend more time embracing life rather than searching for a fountain of youth.
These are only a few of the resources we could reclaim from senescence and death and spend instead on living.
Sadly, "do we need death?" is not a rhetorical question for most people. Acceptance, rationalization and defense of what is - no matter how terrible - are very human traits. There can never be too many people hammering on the points that Rainbough Phillips makes, the same points I and many others make. We need to continue to voice the obvious in order to make it widely heard and understood: that healthy life extension, medical research and the fight to cure aging are possible, plausible, necessary, desirable, greatly beneficial and ultimately ethical activities.
Ivanhoe reports that, barring further upsets, "a United Nations General Assembly panel will vote this Friday, Nov. 19, on an anti-cloning treaty put forward by the United States and Costa Rica." A United Nations ban on therapeutic cloning, a vital technology for the most promising research into regenerative medicine, would be a blow to the fight for freedom of research in many countries - including the US. "We have to listen to our scientists, listen to our physicians and by all means listen to the millions of people that are suffering with diseases. Eventually, this science will advance. I think the question is: How many millions of lives might we lose? How much suffering will take place before we find the true benefits of this research?"
A press release notes a new license and research direction. "Elixir Pharmaceuticals, Inc. announced today that it has licensed intellectual property [relating to] NaCT-1, a human ortholog of the longevity gene, INDY ... Our research suggests that aging is a carefully regulated metabolic process. The INDY gene product is an excellent example of an anti-aging target that has been proven to play a role in the cellular regulation of lipid and carbohydrate metabolism. ... a drug that inhibits NaCT-1 may provide a pharmacological means to reduce fat and cholesterol synthesis and thus enable control of [excess lipids, cholesterol and body fat] ... Elixir has an interest in the NaCT-1 transporter as a drug target for the development of pharmaceuticals to improve human health and prolong youthfulness."
Michael Cooper wrote to me to point out his research that suggests calorie restriction (CR) does not in fact work to extend life span in houseflies:
It is widely believed that CR extends life in all species. But, it does not. My work in Musca domestica (houseflies) reveals that CR does not extend their lifespan.
In fact this work raises questions about the claims in other species as well. For example: in drosophila [fruit flies], they claim significant effects of CR, but no one has been able to directly measure the food the flies consume, the amounts are simply too small. So instead, drosophila researchers use food dilution as a mimic for CR. I believe this tactic is used in other smaller species as well.
FASEB J. 2004 Oct;18(13):1591-3. Epub 2004 Aug 19.
Effect of caloric restriction on life span of the housefly, Musca domestica.
Cooper TM, Mockett RJ, Sohal BH, Sohal RS, Orr WC.
Department of Biological Sciences, Southern Methodist University, Dallas, Texas 75275, USA.
Caloric restriction (CR) has been found to extend the life spans of a wide variety of species, transcending phylogenetic boundaries. The objective of this study was to test the generality of this phenomenon, using the male housefly as an insect model in which food intake can be quantified precisely. Sucrose was found to promote a longer life span than diets additionally containing proteins and lipids. Flies were fed sucrose or a more complex diet ad libitum (AL), or in amounts ranging from 50% to 100% of the average amount consumed by young flies. CR shortened rather than prolonged the life span of houseflies, particularly flies fed sucrose only. The rate of oxygen consumption was not affected by caloric restriction or by the exclusion of proteins and lipids from the diet, and the reproductive activity of male flies remained unchanged by sucrose feeding. Thus, it is unlikely that the life-shortening effects of CR can be explained either in terms of an adaptive response in metabolic rate or use of a suboptimal food source. Results of this study contradict the widely held view that CR has a life-extending effect in all species.
PMID: 15319362 [PubMed - in process]
In the discussion section of this paper, the problem of inability to directly measure food intake in small species is addressed.
Reason, I work with both drosophila and houseflies. My major efforts are actually with drosophila. I do genetic engineering, molecular biology, with drosophila, trying to understand the aging process. So, I am intimately familiar with the care and feeding of this species.
In mice CR, the food is directly measured. As far as I know, all mammal studies have used direct measurement of food. It is in the small species that direct measurement becomes impractical. Houseflies may be close to the practical limit for direct measurement.
There are other more complicated ways of determining food intake, such as; radioactive or other means of labeling. So far as I know, these labeling methods have not been used in CR studies.
The plot thickens. There are certainly a number of studies indicating that fruit flies do experience the benefits of CR - but doubts raised over experimental methods would mean that a more rigorous examination of those findings is called for. On the other hand, if it were the case that fruit flies benefit from CR while houseflies do not ... well, that would seem to be a difference worth investigating more closely. Pinning down the biochemical and genetic roots of CR will have long term benefits for our health and longevity - hence all this careful work with flies.
EurekAlert notes that UCLA researchers have demonstrated that telomerase - a telomere-extending protein - can be used to prevent the premature aging of the immune system. "Immune cells that fight HIV are under constant strain to divide ... This massive amount of division shortens these cells' telomeres prematurely. So the telomeres of a 40-year-old person infected with HIV resemble those of a healthy 90-year-old person." This sort of premature aging is the result of a part of your body running at an accelerated rate - but with telomerase, "immune cells could divide endlessly. They grew at a normal rate and didn't show any chromosomal abnormalities that might lead to cancer." This research opens up possibilities far beyond the obvious benefits to HIV-infected people.
There are two pieces of good news for embryonic stem cell science in this report from the The Australian. Firstly, a Melbourne company is allowing free, unconditional access to a new embryonic stem cell line, with more to come in the future: "The company planned to release five more stem-cell lines over the next two years." This is an interesting varient on open source development strategies; the company plans to profit indirectly from its altruism. Secondly, this line only cost $100,000 to develop! This comparatively low price point (itself a sign of advancing technological prowess in the field) indicates that we should be seeing many more lines becoming available in the future - an essential condition for real progress in regenerative medicine.
When Penn State researchers made small changes in young women's meals -- reducing calorie density by 30 percent and serving size by just 25 percent -- the women ate 800 calories less per day and felt just as full and satisfied.
Dr. Barbara Rolls, who holds the Guthrie Chair of Nutrition in Penn State's College of Health and Human Development, directed the study. She says, "We lowered the energy density, or calories per gram, of the participants' meals by incorporating more vegetables and fruit in recipes and also using food products reduced in fat and sugar. The subjects found the smaller, lower energy density meals just as palatable, filling and satisfying as the big, high calorie menu items -- and they didn't compensate for lowered intake on the first day by eating more on the second day of the study."
If you were eating a nominally sane (say, 2500 calories per day) diet and dropped 800 calories per day, you'd already be into calorie restriction territory. As practitioners have been saying for a while, it's quite possible to do this without feeling hungry if you are sensible about what you eat.
The CR Society conference took place last week, and by all counts it was a successful event. The CR blogs commented from the convention and afterwards. Here are another couple of entries. Those blogs are mostly food- and lifestyle-focused; very useful for practitioners and newcomers, but somewhat light on convention details.
You'll find the details, including some lengthy convention reports, by searching the archives of the CR Society mailing list. I can't link directly, unfortunately - it would be nice on a number of levels if the society administrators would liberate the list archives from that onerous login requirement.
I have it on good authority that we'll be seeing presentations and transcribed reports from the convention in a more accessible form fairly soon. I'll link to them when they are up.
While I'm on the subject, it's worth noting that Brian Delaney - CR Society president - has collaborated with Lisa Walford on a new calorie restriction book aimed at newcomers.
At last, here's a book that synthesizes the increasingly popular CR (Calorie Restriction) diet for the layperson. CR is not a diet primarily about weight loss, although readers will lose weight. CR is about eating highly nutritious foods in smaller quantities to extend your healthy years. Here's the concept: eat less, but choose foods more carefully. This will "upregulate" your metabolism; in other words, what goes in will be used more economically. Dieters will feel better and function better - and the big bonus: the CR diet slows aging. CR lengthens the periods of youth and middle age and substantially reduces the risk of virtually all the diseases of aging. Lisa Walford and Brian Delaney, two longtime CR practitioners, will take you on a handheld stroll through the process, including an introduction to CR, how to do it, some of the key issues in the current dialogue, and the skinny on superfoods.
I'm not sure we can claim the stronger scientific sense of the word "proven" on "slows aging in humans" yet, but we're close to being able to say something like this based on recent research. There is certainly a strong presumption amongst respectable researchers that CR should slow aging in humans, just as it does in all other species science has tested. Regardless, I don't see anyone jumping up to dispute the greatly reduced risk of age-related disease or other health benefits provided by CR at this point; that's pretty much in the bag thanks to the CALERIE study.
The Life Extension Foundation News relays some interesting statistics on the health and lifestyle history of participants in the New England Centenarian Study. The majority (80% or so) of those who reach the age of 100 have survived age-related conditions - often for decades - rather than avoided them altogether. This would seem to indicate that genetic and other factors are as important as suspected: "Delaying the onset of these diseases or escaping them entirely does not seem to be the only assurance of a very long life. ... brothers of centenarians are 17 times more likely, and sisters 8 times more likely, to live to at least 100 than the general population."
The Times lavishes attention on resveratrol, one of the current darlings of the anti-aging marketplace. "It works by binding to a class of proteins called sirtuins which regulate the repair of cells and dramatically boosts their efficiency. Studies have shown that it has an impressive anti-inflammatory action which, in animals, has delayed the process of ageing and increased lifespan by up to 50%." While researchers see promise in a compound that appears to mimic some of the effects of calorie restriction, most responsible observers are suggesting it would still be premature to run out and buy resveratrol supplements. Efficacy in the laboratory is a fair way away from the proven benefits of supplementation.
The findings suggest that DHEA replacement therapies could reverse some of the hormonal and metabolic changes that come with aging and cause abdominal fat to accumulate more easily.
Since levels of DHEA decline with age, supplementing to maintain youthful levels is thought by some to be a valuable antiaging strategy. DHEA is currently widely available as a dietary supplement, after it was banned by the FDA in 1985 due to a lack of scientific proof that it was safe for over-the-counter sale as a drug.
There has been debate over the value of DHEA supplementation, and some think that it may be harmful. DHEA eventually converts into testosterone and estrogen, for example, so might increase the risk of prostate tumors in men and ovarian cancer and heart disease in women.
While the new study suggests that DHEA supplementation could have valuable therapeutic benefits, the researchers involved admit that it was run on too small a cross-section of participants to be considered anything more than preliminary. They are currently planning more long-term, large-scale studies to determine possible negative side-effects.
I think the Wikipedia entry cuts more directly to the chase, however:
The significance of the hormone in health and disease is not fully established. It is postulated that substitution of it can be beneficial in a number of disorders
However, there is too little scientific proof to advocate the use DHEA outside specialist centres under careful observation of experts in the field of endocrinology.
DHEA has long been a favorite of the old school healthy life extension community (as for other line items, in the absence of what I would consider sufficient scientific backing for commonplace use). I think that the diversity of studies and results for varied hormone treatments indicate that we don't fully understand the mechanisms and consequences of such treatments, and that results vary widely between people.
Hormone-related treatments like this seem to be a case of pulling the unmarked big red lever on the side of the complex machine. We need more research - but I suspect there are better areas on which to focus resources than homone-related supplements.
BusinessWeek provides a reality check on progress in commercial research and development of stem cell based regenerative medicine. "The politicization of this has created a whole field of overnight experts who have no clue what they are talking about. Most of them have never seen an embryonic stem cell." The article makes that case that gains in the market due to the passage of Proposition 71 are largely misguided investor enthusiasm - a closer look is required before taking any of it at face value. Commercialization of medical advances is a long, hard road; there is a way to go yet for even the earliest and most promising stem cell therapies.
Some of the most important medical research taking place right now is also the most basic - learning to understand and control cells and cellular processes. Here, the Boston Herald looks at work on clams and its relevance to future medicine: "The clam eggs are the key. They give scientists an extraordinarily good look at a process that's fundamental to living organisms, from baker's yeast to humans: cell division. When things go wrong in cell division, it can cause disease. ... That's a vital first step in using the clam to discover the root causes of baffling human ailments, including cancer, muscular dystrophy, premature aging and diabetes. ... The molecular basis for disease might be variable. We're trying to understand all the molecules involved."
As long-time readers will know, all advertising revenue from Fight Aging! and the Longevity Meme is donated to the Methuselah Foundation. Currently, this money goes to help build the Methuselah Mouse Prize fund.
Our latest sponsor (you'll see their banners starting next week) is asking about other opportunities for advertising beyond the standard header banner you no doubt see at the top of this page. Examples included paid placement in the Resources section of the Longevity Meme, inclusion of links to sponsor articles, the inclusion of advertisments in the Longevity Meme newsletter and so forth.
I think that any sort of paid placement is a bad thing - it always has been a bad thing in search engines, for example. It subverts the useful original purpose of the places in which it occurs. Similarly, there is such a thing as too much advertising for a given website. However, inclusion of modestly sized text ads in the Longevity Meme newsletter seems like a reasonable step - assuming that the subscribers are on board with such a change. What else could fall into that category without stepping over the line?
I'm throwing this open to the gallery - what do you folks think? Ultimately, these sites are here for your benefit, so your suggestions and ideas are welcome.
The BBC singles out one area in which attitudes towards later life must change: "We live in an ageist society and it is a society that has not adjusted to the increased life expectancy that we have." If advocates and researchers are successful in ensuring even greater gains in life span over the next few decades, the need for change will become more pressing. This is not to say that the top-down legislative approach is the right one - far from it, since it is precisely these top-down policies (such as fixed retirement ages and Ponzi-scheme benefits) that cause many of the current problems. Advocacy, education and the increasing ability of fit, healthy, smart seniors to participate in society should do the job in the long term.
As reported at CNN, US ambassadors to the United Nations are still pushing hard for a vote to ban therapeutic cloning: "A General Assembly panel is headed for a close vote next week on a plan for an anti-cloning treaty put forward by the United States and Costa Rica." This technology is vital to much of the most important stem cell research - including attempts to cure common age-related degenerative conditions. While a UN ban would likely be ignored by countries like the UK, it would provide further impetus for pending criminalization of research in the US. I strongly suggest that you contact your elected representatives and let them know exactly what you think of these dangerous, anti-research initiatives.
S. Jay Olshansky was kind enough to comment on one of my Fight Aging! posts critical of his mainstream media declarations on the prospects for healthy life extension. This extended into an educational three-way commentary between myself, Olshansky and Aubrey de Grey (proponent of the Strategies for Engineered Negligible Senescence initiative). We each have interesting differences of opinion on this topic - differences that I feel have a material effect on the prospects for funding in rejuvenative research. If you take an interest in the way in which science, activism, funding, the mainstream media and healthy life extension interact, I suggest that you take a look.
An article in the Guardian provides the European take on the passage of Proposition 71 in California. "People decided they weren't interested in waiting, that this science needed to be pursued aggressively. They said if the US isn't going to do this as a country, then let's make California do it. ... In some respects, Proposition 71 is one of the great bright lights of this election, it's a very healthy amount of money and we're very pleased it got passed. The problem is, it's so healthy, that those of us outside California are pretty concerned. What do we do to compete?" I'm still of the opinion that removing the threat of criminalization is more important than providing government funding - since the potential private funding pool is much larger.
I still have high hopes for positive change in the cryonics industry - greater professionalism, better organization and more basic research - based on events of the last year or two. On the basic research side, Suspended Animation, Inc, a company funded by Saul Kent of the Life Extension Foundation, was supposed to get underway earlier in the year. You may recall the series of setbacks and resulting second-guessing based on refusal of a zoning permit in Boca Raton.
So it seems that Suspended Animation, Inc is still essentially in the setup phase:
After getting an icy reception from Boca Raton last year, a company hoping to perfect techniques for freezing dead people with the hope of someday bringing them back to life is paring its plans and considering lab space in Boynton Beach.
Suspended Animation Inc. informed city planners this year that the company intended to lease space at 3020 High Ridge Road for biomedical research. The cryonics research firm has since applied for, but has yet to receive, a city occupational license. Now, Boynton Beach city commissioners want company officials to appear before them to elaborate on their research plans and answer commissioners' mounting questions.
One can hope that they will overcome the business location hurdles fairly soon and get to work on improving cryonics technology - and generating sensible spin-off products. If this industry is to grow, basic research is essential.
S. Jay Olshansky was kind enough to comment on one of my previous posts. After a short exchange of e-mails to clear up misconceptions on both sides, I sent this reply:
Let me start by saying that at no point and in no way am I criticizing the procedures or conclusions of this research, and I do appreciate you taking the time to address these issues. In the piece you singled out for comment, I was holding up your figures on obesity and cancer as a point well worth thinking about, while mentioning that I don't agree with other items - independent of your research - as discussed below.
In addition, I bemoaned the inability of media articles of this sort to responsibly discuss the technology curve associated with medical science. The NIH projects that cancer will be largely treatable by 2015, and responsible scientists in the field of regenerative medicine expect to be able to repair age-related damage to major organs by 2020 or thereabouts. This is what I mean by "fails, like most, to consider the effects of current technological development on historical and short term trends." I find it very frustrating that most science journalists limit themselves to joining the dots and extrapolating from there.
I can see where the language in that third paragraph on the page you commented on could be misleading if you are unfamiliar with my previous remarks on your views as they are presented in the media. I have put in an edit to make things a touch more clear.
But on to my chief criticism, unrelated to your research. This relates to your numerous representations in the media on the dim prospects for extending the healthy human life span through medical research. In particular, I think this following piece gets to the heart of my objections to the way in which you present your case to the mainstream media:
It is, I suppose, possible that you are consistantly being misrepresented and quoted out of context in the press. You are, however, one of the most quoted scientists in the mainstream media in the field of aging research at the moment, and it is your responsibility to ensure that your views are reproduced accurately. Most people in the world get their information about progress and prospects in healthy life extension through the mainstream media. They base their support and desire for further research on this information. This in turn drives the engines of public and private funding processes. By putting an unreasonably conservative position forward to the world in this fashion you greatly damage the long term prospects for funding in this field.
Based on media analysis and number of appearances, I'd say you are currently about as influential on the common view of the future of extending the healthy human life span as either Leon Kass or Ronald Klatz. Unfortunately, like both of these characters, your net influence on public support for serious healthy life extension research is negative. Now, this may or may not be independent of your actual views on the subject and supporting science you have worked on. However, I don't just speak for myself here - the wider community of which I am a part has come to place you on a par with Leon Kass (unfairly or not, based on your appearances in the media) in terms of your views and influence. I get fairly sharp e-mails whenever I mention you on my site.
I take activism for longevity research very seriously, and I am always greatly disappointed when scientists take it upon themselves to sabotage the rate of progress in this fashion. There are more than enough varieties of people out there already working hard to cut the legs out from underneath directed rejuvenation research.
If you sincerely believe that extending the healthy human life span is as difficult and remote as you represent to the world through the mainstream media, the responsible thing to do is - rather than continue to push your position in the press - to engage in debate with those scientists who hold the opposite view, such as Aubrey de Grey. After all, the worst that could happen is that you prove yourself to be right.
In his comments on my previous post, Olshansky mentioned that he does in fact sign on to the healthy life extension agenda:
"We enthusiastically support research in genetic engineering, stem cells, geriatric medicine and therapeutic pharmaceuticals, technologies that promise to revolutionize medicine as we know it. Most biogerontologists believe that our rapidly expanding scientific knowledge holds the promise that means may eventually be discovered to slow the rate of aging. If successful, these interventions are likely to postpone age-related diseases and disorders and extend the period of healthy life. Although the degree to which such interventions might extend length of life is uncertain, we believe this is the only way another quantum leap in life expectancy is even possible. Our concern is that when proponents of antiaging medicine claim that the fountain of youth has already been discovered, it negatively affects the credibility of serious scientific research efforts on aging. Because aging is the greatest risk factor for the leading causes of death and other age-related pathologies, more attention must be paid to the study of these universal underlying processes. Successful efforts to slow the rate of aging would have dramatic health benefits for the population by far exceeding the anticipated changes in health and length of life that would result from the complete elimination of heart disease, cancer, stroke and other age-associated diseases and disorders."
So I look forward to seeing this view reflected in his future appearances in the mainstream media...
Competition is what keeps people comparatively honest and working hard, even in government it seems. Newsday reports on competition between biotech hubs in California and New Jersey in the wake of Proposition 71 funding for embryonic stem cell research. New Jersey business developers are concerned that many biotechnology companies will move work to California - which seems very likely under the circumstances. Massachusetts politicians are also under pressure to make their state more hospitable to stem cell research. So while the threat of federal anti-research legislation remains, it looks like state legislative environments will become less threatening where it matters.
From the long term perspective, the most basic stem cell research taking place at the moment is also the most important: "We want to learn more about stem cells over the lifetime of a human and why they seem to quit working as we age. Is it because the stem cells are becoming depleted. Is it because stem cells are dying out and not being replaced? Is it because you have other hormones being produced that interfere with the action of stem cells?" The range and effectiveness of potential regenerative therapies will expand as we learn more about stem cells - how to control them and how they actually work. With that in mind, it's good to see that research programs are underway.
I'm willing to bet that the first widely available regenerative therapies based on stem cell research will be adult stem cell transplants of some form or another. The research is going well:
Results from an animal study conducted at Johns Hopkins show that stem cell therapy can be used effectively to treat heart attacks, or myocardial infarcts, in pigs. Stem cells taken from another pig's bone marrow, when injected into the animal's damaged heart, were able to restore the heart's function to its original condition.
A number of other approaches to regenerating damaged hearts - based on the same theme of transplants or culturing the patient's own stem cells for reimplantation - are in trials or late stage research. Some are looking very promising.
Repairing currently irrepairable heart damage is a big deal in and of itself, but scientists will be able to do far better than this in the years ahead - assuming that the obstructionists get out of the way and freedom of research is maintained.
Intriguing research into the mechanisms of age-related mental decline is discussed at Betterhumans. Scientists have identified a very low-level process in neurons that can be tweaked to at least partially negate "the cognitive decline that affects about 40% of people over 65. Although scientists don't know the exact cause of age-related mental decline, studies have implicated decreases in neuronal excitability as well as decreases in synaptic plasticity - basically, the ability of brain cells to change connections. ... the ion channel-altered mice retained neuronal excitability into old age and had greater synaptic plasticity." This is early stage work, of course, but - like all research on the brain - very important to the big picture of regenerative medicine.
A recent study on fish from areas of high and low predation is challenging evolutionary theories of senescence, the rate at which animals degenerate with age. "We instead found that senescence was a mosaic of traits. ... The composite picture is that all of these fish deteriorate with age, but the comparative rates of deterioration is a mix of responses, most of which do not correspond to classical theory." As is usually the case, an aspect of biology is proving to be more complex than first imagined. "The differences between these results and the classical predictions gives cause to take the new, more derived, theories for the evolution of the aging process more seriously."
I was intending to title this post "How Far Down the Rabbit Hole?" but decided that was unfair to many of those in the business of optimizing health and healthy life span through presently available technologies. I currently have my hands on a review copy of Fantasic Voyage: Live Long Enough to Live Forever, the book by Ray Kurzweil and Terry Grossman. You may recall that I am unhappy with the strong focus on old school ("Bridge One" in their terminology) technologies, medical knowledge, and health optimization via supplementation.
I have to throw up my hands at this point. The world has more than enough people who are taking the Life Extension Foundation, A4M and similar paths. We don't need more sellers of vitamin shakes. I think that history demonstrates that when dedicated advocates for healthy life extension research start to focus on old school technologies, their fervor and original message becomes diluted and lost. They change into simple health advocates focused far more on selling largely ineffective present day technologies than supporting medical research goals for the future.
That shouldn't stop you from stepping out to pick up a copy, however. If you are someone who found a book like Roy Walford's Beyond the 120-Year Diet useful, then you will probably get just as much out of Fantastic Voyage. In it's own way, it's a big step forward for the realm of lifestyle and health advocacy, explicitly taking on and discussing transhumanist ideas associated with extending the healthy human life span. The focus is, however, very much on Bridge One / the old school, with the expectation that staying healthy for another twenty years will bring you amazing further benefits due to new medical science.
My suspicion has always been that this approach takes future advances in medical technology - and the rate of advancement - too much for granted. I don't think it is a given that we will achieve the goals required for radical life extension soon enough to help those of us alive now. Advances in specific fields of medicine require widespread public support to drive the necessary large-scale funding, whether that funding is private or public. (From the other side of the coin, it's possible that folks like Ray Kurzweil think that I take the implementation of Bridge One/old school technologies for granted - but I look out at the world and see any number of people working hard on that problem, while all too few are looking to the future).
So how much time should you spend working on optimizing your own health - using what are, frankly, pretty crude tools in the grand scheme of what is possible - versus working to accelerate medical research and bring about healthy life extension more rapidly? This is very personal decision based on a number of factors, and I don't attempt to discuss it at great length at the Longevity Meme. To pick a few:
Do you have enough money to buy supplements and access to medical technology now with an unknown chance that they will work as advertised? Would you be better off saving most of that money for future healthy life extension procedures that may turn out to be pretty expensive?
There is no reliable way (right now, in any case) to evaluate the effects of lifestyle and medical choices aimed at prolonging your healthy life span - short of waiting, that is. What do you consider reasonable evidence for a good chance of effectiveness? How effective per dollar expended does a treatment or lifestyle choice have to appear to be before you would adopt it?
Many people obtain great satisfaction from tinkering with supplement regiments and other old school technologies for health. It's much like working on a car - only you don't find out whether you're actually getting that last 10% of extra performance until it's too late to make a difference. I suspect that the lack of cut and dried answers makes it all the more appealing to a certain set of people.
For my money, as I've said before, I suspect that we can't presently do much better than well thought-out calorie restriction, moderate exercise, a good relationship with your physician, and sensible, moderate supplementation - at a cost of at most a few hundred dollars a month, and probably much less, depending on your definition of "sensible, moderate supplementation." You can work a great deal harder and spend a lot more money, but what will you have to show for it? It's a big point to argue, and many people spend a lot of time and effort doing just that.
I think we can do better. I say put all that extra effort into supporting medical research for longer, healthier lives. Future technologies to greatly extend your healthy life span won't come about any faster if you are spending your time and money tinkering ever-finer gains out of 20th century supplements and lifestyle options.
Researchers at Columbia University Medical Center are "confident that we may be closing in on new Alzheimer's genes." If verified, these would be the first genes found to increase Alzheimer's risk in a decade: "Researchers think that Alzheimer's is caused by the interaction of several different genes, but so far only one gene, ApoE4, has been linked conclusively to the disease. Finding the other genes will be a huge step toward understanding how Alzheimer's begins and how it can be treated." Modern bioinformatics allows scientists to work rapidly towards understanding the mechanisms of a condition from the basis of identified genes, so genetic discovery is a noteworthy landmark in the research process.
Wired reports on the US ban on therapeutic cloning, a single Senate vote away from becoming law since 2003. "Brownback's and Weldon's legislation would outlaw therapeutic cloning in the United States. The bills would also ban importation of any medical products created using the technology in other countries. Punishment would be up to 10 years in prison and a $1 million fine." Therapeutic cloning is vital to much of the most important research into regenerative medicine and cures for age-related conditions. This pending ban has done a great deal of damage to private investment in stem cell research - it's time for it to be removed. Contact your elected representatives today!
The Monterey Herald reports that research institutions in California are off to a quick start in the competition for state funding authorized by Proposition 71. It is likely to take six months or more for anything to happen at the government level, but preparations are underway. The article emphasises the importance of therapeutic cloning - a technology still under threat of criminalization - to research into curing age-related disease. "There are many human diseases, like Alzheimer's or Lou Gehrig's, that are genetic diseases. We are even honing in on some of the genes that might be involved." But without therapeutic cloning, "We don't understand how the disease develops and how to go in the direction to find cures for those diseases."
An article I noticed earlier today reminds me that the process of changing popular views on later life is an important part of generating wider public support for medical research into healthy life extension.
In 1900, average life expectancy in America was 49.2 years. Today it's 76.9 years. But Americans are not only living longer, now they're staying healthy longer. In the process, they are not only shattering old stereotypes, but redefining what it means to grow old in America.
"What are you supposed to do, sit around and die?" says Smith, 75, the owner of a 1973 Harley Davidson. "I don't think so. I've got too much to live for."
Consider that iconic vision of old age depicted in James Whistler's famous portrait of his mother, known as "Whistler's Mother." She is shown seated, grim-faced and feeble, with a lace cap covering a down-turned head. She was only 67 when she posed for the painting.
Now, consider Vera Gagen. She's only 54, though she could easily pass for 10 years younger. She's riding horses. She's taking salsa dancing lessons. The rocking chair is a long way off.
The stereotypes of later life held by many people - young and old - go a long way towards suppressing support for medical research into the aging process. Why live longer if it means more years as Whistler's Mother? In reality, of course, the era of later life as illustrated by Whistler's Mother is already long gone - but the stereotypes linger. 70 may be the new 50, but that hasn't quite sunk in yet for many people who have yet to get there.
The demonstrable improvements in quality and length of life achieved in past decades should be inspiring people to support more medical research aimed at greatly improving and speeding the process of healthy life extension. Advocates, futurists and scientist must keep working to ensure that this is the case.
From the Life Extension Foundation News: "Aubrey de Grey reckons 'we have a 50-50 chance of developing a human rejuvenation therapy that works.' His timetable calls for 10 years to prove the scheme works for mice, and another five years to apply the techniques to humans. From then on, 'radical life extension' will mean 'the indefinite postponement of aging.'" On the other side of the coin: "Olshansky believes it is misguided to regard aging as a 'disease' that can be 'fixed.' Instead, he sees it as the inevitable result of irreparable cellular damage that is a byproduct of living." Olshansky's views are widely regarded as indefensible - some cellular damage can already be repaired, and the research required to repair the rest is not a mystery.
Robert Fogel will be speaking in Berkeley later this month on the economic implications of increasing healthy life span and better medicine over the course of the 20th century. A choice quote: "Fogel argued in a recent lecture that assessments of economic gains over the past 130 years should include the 50-percent likelihood that a U.S. student today will reach the age of 100 'in good health.'" This is, of course, a very conservative projection given current research trends. Increased life span brings greater opportunities for wealth and further increases in life span: "The advances in the first half of the 20th century have been greatly underestimated because economists have concentrated on wealth but ignored gains in health and longevity."
EurekAlert examines advances in our understanding of cellular recycling: "This process of internal house-cleaning in the cell is called autophagy - literally self-eating - and it is now considered the second form of programmed cell death." Like many cellular mechanisms, this turns out to have relevance to cancer and aging. "Laboratory mice with suppressed autophagy also appears to have a higher rate of spontaneous tumors ... Autophagy activity is known to decrease with aging ... Conversely, more autophagy may prolong life. This fits with findings that caloric restriction can extend the life span in rats, since near-starvation triggers more autophagy as the cells recycle parts of themselves for fuel."
In the midst of a pessimistic article about future trends in life span (that fails, like most, to consider the effects of current technological development on historical and short term trends) we find this item for consideration:
Obesity, [Olshansky] said, is "a global pandemic" that's already reduced life expectancy worldwide by 3.5 years. The effect of obesity on longevity is about the same as cancer, he said, and will double or triple in coming years, shortening lives by seven to 12 years.
Now I certainly don't agree with most of Jay Olshansky's propositions. His views on the possibility of increases in life span through directed medical research into the aging process are very unreasonable and he has not yet defended them in a rigorous fashion.
EDIT: Just to be clear here, I'm not disagreeing with Olshansky's conclusions regarding obesity and its effects on life expectancy, or calling into question this piece of research. What I do take issue with are his representations in the media regarding the dim prospects for healthy life extension through medical research. I - and to a lesser extent the scientists below - are skeptical about a decrease in overall life expectency because we expect to see gains due to advances in medicine.
Even other scientists who are not looking towards a future of radically increased healthy life spans are criticizing the projections made in this article:
"The modern era of dramatic increases in life expectancy is about to come to an end in the developed world - including the United States - as well as in the underdeveloped world," said Jay Olshansky, a demographer at the University of Illinois in Chicago.
"Life expectancy might very well decline in this century," he told last month's annual meeting of the Institute of Medicine, a branch of the National Academy of Sciences in Washington.
"Biology can play out quite differently in different countries at different times," said Richard Suzman, associate director of the Institute of Aging at the National Institutes of Health.
"Jay Olshansky's position is a minority perspective in demography," Suzman added. "However, majority positions in science sometimes turn out to be wrong, and so minority positions should certainly be entertained."
"There is a small chance - less than one in 100 - that Olshansky's prediction of declining life expectancy might possibly prove correct," Vaupel said.
Another skeptic is James Oeppen, a researcher at the Cambridge Group for the History of Population and Social Structure in Cambridge, England.
"If Dr. Olshansky is correct, he won't have to share the accolades with a large group of like-minded contemporaries," Oeppen scoffed.
Still, one cannot argue that excess weight in the form of body fat has been shown to be very harmful to your long term health. It greatly raises the risk of suffering all of the most common age-related conditions, shortens your healthy life span and increases your medical costs. I think that pointing out the comparison to cancer in terms of effect on life expectency is a powerful motivating argument. It's certainly something to think about if you are one of those people who needs that extra something in order to work towards better diet and lifestyle choices.
For those folks in the UK, it's worth noting that biogerontologist Aubrey de Grey will be giving a presentation entitled "Promotion of life extension research via the Methuselah Mouse Prize and other methods: recent progress" at the next ExtroBritannia event on November 28th.
Promotion of medical research aimed at extending the healthy human life span is some of the most important work in this arena at the moment. From a technical perspective, the path ahead is as about clear as it gets in medical science. It's clear that it is possible in principle to greatly extend healthy life span in humans, and it's clear where the basic research needs to start. The obstacles in the way of longer, healthier lives for all are the lack of funding, education and public support for serious anti-aging research.
(From EurekAlert). An accurate and easily measured biomarker for the aging process would be an important step forward, and researchers may have found one: "As cells and tissues age, the expression of two proteins called p16INK4a and ARF dramatically increases. This increase in expression, more than a hundredfold in some tissues, suggests a strong link between cellular aging and the upregulation, or increased production, of p16INK4a and ARF. ... Both p16INK4a and ARF are known potent tumor suppressors, or proteins that halt tumor cell growth. The study suggests that the important anti-cancer function of these proteins to limit cellular growth might in turn cause aging. ... the increase in p16INK4a and ARF can be substantially inhibited by decreasing caloric intake, a known retardant of aging."
Commentary on recent Alzheimer's research can be found over at FuturePundit. "Injected antibodies might avoid the side effects produced by vaccination against Alzheimer's amyloid plaques. ... While the Elan Pharmaceuticals experimental vaccine AN-1792 against Alzheimer's amyloid plaques caused brain inflammmation in a small subset of people treated I still think a better vaccine may be able to eventually work well against amyloid plaques. In fact, a new oral vaccine has just been tested in mice and shows promise." Some other good points are made regarding the payoff from investment in medical research - it's always better in the long term to be doing more to cure age-related degenerative conditions.
Betterhumans reports on interesting developments in telomere research. Telomeres serve as protective caps for our chromosomes and regulate planned cell death. They also become shorter throughout the body as we age. "Researchers Mariuca Vasa-Nicotera, Scott Brouilette and colleagues from the University of Leicester in the UK have linked differences in telomere length in humans to a region on chromosome 12." In addition to the aging process, cancer development has been linked to shortened telomeres. Establishing a good candidate gene for telomere length may open the door for genetic therapies to lengthen telomeres - something that biogerontologist Aubrey de Grey considers an important advance in the fight to cure aging.
From MENAFN, commentary on the significance of medical research currently taking place from biotech writer Gina Smith. "Look at what [Cynthia Kenyon is] doing. Molecular geneticists like her are already helping identify the proteins that inhibit aging in animals. I can't believe we won't make improvements in human anti-aging treatments in the next 100 years. ... The premise is that we can slow down the aging process. And if we can do that, we can reduce the risks for all kinds of diseases. Cancer, heart disease, osteoporosis - the risks for all of these go up as you get old. But if we can slow down the aging process, we can reduce risk." The basic research taking place now is vital to the future of longer, healthier lives - but we must see more directed and less incidental healthy life extension.
What to expect from the interventionist US government over the next four years in areas of relevance to healthy life extension and medical research? As I said last week:
Whoever is elected to office following the November US election, whichever way the UN jumps on therapeutic cloning, and whatever the result of the Proposition 71 vote in California, the mechanisms of government capable of restricting medical research will still be in place. The degree to which medicine is socialized - and thus slowed, hobbled and held back from the best possible pace of advance - will remain largely unchanged. Most of the threats to the future of your health and longevity will still be there, personalized by the same government employees and rules that existed before the election.
In his recent commentary on science policy at Reason Online, Ronald Bailey proposes that matters will remain much as they are now:
President Bush limited federal funding for research on human embryonic stem cells to colonies of cells that had been derived before his speech on the topic on August 9, 2001. To date, only some 22 colonies of stem cells have qualified for such funding. With the bioluddite Leon Kass, head of his Council on Bioethics, whispering in his ear, President Bush is unlikely to change his position on this issue despite the fact that recent polls show that a majority of Americans favor more federal funding for stem-cell research. The passage of California's Proposition 71, which establishes a $3 billion state fund for stem-cell research, is an interesting exercise in federalism which Bush will likely ignore.
Of the 22, almost none are useful - and hundreds or thousands of lines are needed for serious progress in any case. Federal funding is far less important than private funding; what is really needed now is for governments to step back from trying to ban therapeutic cloning and related medical research. These anti-research efforts have been effectively scaring away private funding for years now.
On the topic of pro-death bioethicist Leon Kass, wider bioethics and anti-research forces in government, the the american journal of bioethics editors blog has a few choice words:
There is still one winable battle, although I fear it is not in Ohio or Iowa. The battle is to reform or reject the President's Council on Bioethics. Leon Kass is no doubt gearing up to lead all the President's ethicists for another term of moral seriousness. He must be put on notice that bioethics cannot afford four more years of feckless, xenophobic neocon posturing.
The PCB literally ignores the entire literature in bioethics in its writing. Wait, I forgot, they did cite Carl Elliott a couple of times. But it is shameful to see the degree to which they ignore - as in do not respond to at all - those who do not agree with them entirely. This Council must go, or at least be made to play a peripheral role in the bioethics scene, unless it is radically remade with voices from both sides of the aisle.
Is there anyone who doubts that the Leon Kass who spoke on behalf of the President's policies openly during an election season will seize upon Bush's "terminal presidency" to push for real actions that could really set back stem cell research and even IVF? I don't.
It is a pretty terrible day for those of us in bioethics who supported the right to choose, hES research, and dozens of other areas I have not taken the space to discuss.
A concern I have voiced before (Chris Mooney also) is that federal organizations have shown themselves very willing to intervene in conflicts between local and federal law: personal drug use, medical decisions, patients rights and privacy are all fair game, and more restrictive federal laws have won out. There are anti-research laws just waiting to be passed that would conflict with local support for medical research - such as California's embryonic stem cell research initiative. We have seen federal raids before - will we see federal agents raiding laboratories and arresting researchers who are working to cure age-related conditions?
It's an ugly possibility, but it is a possibility.
(From bio.com). In a clever piece of work, scientists have demonstrated that the natural mechanisms of stem cells can be used to deliver gene therapy to tumors in the body. "The researchers then used a virus to deliver a particular gene that has therapeutic action against cancer into the stem cells. When given back through an intravenous injection, the millions of engineered mesenchymal progenitor cells engraft where the tumor environment is signaling them, and then activate the therapeutic gene." This is quite ingenious, utilitizing the normal stem cell response to injury that has been subverted by cancer in order to grow tumors. "This drug delivery system is attracted to cancer cells no matter what form they are in or where they are."
MSNBC reports that California Proposition 71 has passed. "Proposition 71 authorizes the state to sell $3 billion in bonds and then dispense nearly $300 million a year for 10 years to researchers for human embryonic stem-cell experiments, including cloning projects intended solely for research purposes." The current US administration is strongly opposed to this research, and has shown itself willing to intervene in states where local law and federal policies are at odd - in matters relating to drugs and euthanasia, for example. In addition, the long term effects of this proposition, as with all government actions, are far from certain. The fight to support research into regenerative medicine is by no means over.
Healthy life extension is human enhancement, just like efforts to create bigger muscles or better minds. There is absolutely nothing wrong in turning our efforts to improving our lot in life - and better bodies, health and life span are a perfectly valid part of the quest for self-improvement.
In his latest piece at Betterhumans, James Hughes takes a look at the split between forward-looking and conservative factions - over human enhancement, needless to say - in the bioethics and nanotechnology communities. If you're interested in hearing about some of the butting of heads and disagreements going on behind the scenes, then dive right on in.
A battle royale between bioconservatives and transhumanists is brewing in US politics. From ground-zero communities such as bioethicists and nanotechnologists, the struggle for our right to use technology to control our own bodies and minds is spreading.
Of course, I'm not at all fond of bioethics as a field - and I certainly don't see bioethicists as a "ground zero community." Are bioethicists out there performing essential medical research? Of course not - they're the ones consuming fat salaries while trying to stop esential medical research from happening at the best possible speed.
However, some important points are touched on in this article. It is worth remembering that in even "free" societies today, you do not have full legal rights over your own body and mind. You are forbidden from undertaking a great many things, in fact. Medical research and the practice of medicine are similarly constrained. So long as government interference in private lives and contracts is accepted in our societies - thus allowing conservative groups to prevent or slow progress - we will continue to see progress towards healthy life extension technologies that is far slower than it might otherwise be.
The Boston Globe examines the evidence for mitochrondrial damage as a root cause of aging. "The evidence is piling up but not yet definitive. It is grounded in the knowledge that mitochondrial function deteriorates with age, that mitochondria generate damaging molecules called free radicals, and that mutations accumulate in mitochondrial genes, some of them caused by free-radical assault." This is a hot area for research right now - and deservedly so. We need more research funding for important basic science like this! From the conservative side of the science bench: "Mitochondria are a source of energy and a lot of damage. But the body is designed to deal with a lot of this. I'd like to be a believer, but I also have to remain skeptical until we see rigorous proof."
Wired reports on successful efforts to induce the regeneration of neurons in mice: "They induced the birth of new cells by killing nearby neurons in mice, which set off a cascade of events that led to stem cells, also called precursor cells, producing new neurons in the cerebral cortex. If scientists can turn this into a therapy for humans, it would mean that patients could literally heal themselves with stem cells already present in their brains." This initial methodology is not one that would be used in humans; the object here is to study the chemical signals and cellular processes involved. Once those can be replicated, the door is wide open for brain regeneration in humans - and therapies for neurodegenerative disorders like Parkinson's and Alzheimer's.
Joao Pedro de Magalhaes pointed out the implications of recent work on cancer in mice:
It looks like cancer-resistant mice have a normal lifespan and age normally.
http://www.genesdev.org/cgi/reprint/gad.310304v1 (subscription required)
Here's a link to the story on BBC:
This is a very nice work by Manuel Serrano's group in Madrid as it shows that increasing cellular defences against damage, while influencing cancer, does not impact on aging. What it tells me is that aging is not merely a result from damage accumulation. It also raises questions on the link between cancer and aging--one which I've argued for in the past.
This is very interesting, to say the least, but I think it's a little premature to discount damage accumulation as the mechanism of aging - and the benefits of increasing cellular defences.
Dr Manuel Serrano used DNA technology to breed mice that had an extra copy of part of the tumour suppressor genes called Ink4a/ARF locus.
This locus controls the production of two proteins that together appear to stop most human cancer cells developing.
These 'supermice' were found to be extra resistant to things known to trigger cancer, called carcinogens, in normal mice.
Quite aside from all that, I think we should all be cheering the prospect of a genetic therapy that insulates people from developing most cancers!
One item that campaigners and politicians opposed to embryonic stem cell research like to point out is the comparative absence of private funding for this field of science. Well, that funding isn't there because anti-research groups have pushed very hard - and with a fair amount of success - to restrict or outright ban embryonic research and the very essential technology of therapeutic cloning. If you're a venture capitalist, you don't invest in companies that may have their main line of research and revenue criminalized in the near future.
If the prop passes, cash-strapped California taxpayers will be spending their money on a handful of second-rate biotech companies that the smart venture capital money housed around San Francisco's famed Bay Area already passed on. To the smart money, these companies had poor prospects and, in many cases, shoddy or highly speculative science.
That's not to say Wall Street's elite investors didn't make their own investments in stem-cell research. But after years of delays, disappointments, and dead ends, most of the venture capital that once flowed into these ventures is slowing down and awaiting better science to come out of institutions and academic research.
In a page of this sort of commentary, the author somehow neglects to mention that these poor prospects came about due to ongoing efforts to restrict and criminalize this field of research. By his criteria, a company like Advanced Cell Technology is shoddy, speculative and second rate. This is obviously nonsense.
Futurist Ray Kurzweil discusses his views of the path to radical life extension over at PCWorld. While I don't agree with his emphasis on current old school life extension strategies like pills and supplements, Kurzweil has a good vision for the healthy life extension technologies of the future. "There is a connection between my work on longevity and my role as an inventor overall. In order to time my inventions, I became interested in technology trends, and that has taken on a life of its own. ... Based on these models, we can anticipate the emerging role of biotechnology and nanotechnology on our health. That is how Dr. Grossman and I developed our 'bridge to a bridge to a bridge' concept for radical life extension." You and I can help bring these future medical technologies closer by donating to groups like the Methuselah Foundation.
The healthy life extension community is discussed and referenced in many Fight Aging! posts. Understanding a new community can be a fairly slow process for newcomers, however - it certainly took me a few years to find my way around and come to some understanding as to how it all fits together. The following chart is intended to be a rough guide to the territory, showing alignments, overlaps, and groups surrounding the healthy life extension community.
Overlapping balloons in the visualization indicate areas of common interest and communities that share a sizeable number of members. It is interesting to note that, up until comparatively recently, parts of the community were very isolated from one another. The cryonics, calorie restriction, supplement advocates, and anti-aging research and advocacy communities have grown closer only since the advent of the Internet. This modern ease of communication opens up enormous opportunities for growth in the healthy life extension community, since everyone has wider access to the "feeder groups" (libertarians, transhumanists, extropians, dieters, health enthusiasts, and so forth) that are closely associated with parts of the wider community.
Where do new supporters and advocates of healthy life extension come from? Well, from the surrounding groups - such as health enthusiasts and dieters who discover calorie restriction; libertarians and transhumanists who are interested in cryonics and nanomedicine; advocates for established aging research or specific medical research; scientists involved in searching for cures.
Most importantly, the new avenues of communication and community allow many more people to easily learn about healthy life extension, as you are now. A list of the groups shown in the the diagram on this page, along with examples and references, follows:
Aging researchers and research groups examine the mechanisms and theories of aging. Understanding exactly how and why aging takes place will be essential to developing a cure.
Aging Research Advocates:
Aging research advocacy is a large and well funded non-profit sector, including dedicated organizations like the Alliance for Aging Research.
"Anti-Aging" Frauds, Fakes, and Adventurous Marketing:
As always, I draw a firm distinction between real, scientific anti-aging research and the sort of fraudulent nonsense that drives the billion dollar "anti-aging" industry. This populous group works a nefarious influence on newcomers to the community through misinformation, bad science, outrageous claims, and aggressive, adventurous marketing. A good rule of thumb is to refer to Quackwatch when in doubt about any medical information you find online.
Dieters, Diet Interest Groups, etc:
The world sees calorie restriction diets through the filter of weight loss plans, even though that really isn't what calorie restriction is about. The community of dieters is enormous and complex, but many members are finding their way to healthy life extension through the calorie restriction community.
The calorie restriction community is large, active, and has been getting a fair amount of mainstream press attention in 2003 and 2004. You can read our introduction or visit the CR Society website to find out more about these friendly folks.
Cryonics has great application to the medical industry, but there is little commerce between the cryobiology and cryonics communities. Many cryobiologists are very leery of being in any way associated with something that might damage their funding prospects (meaning anything that is in the least bit unusual or out of the mainstream). With the increasing public exposure - and now legislation - of cryonics in 2003 and 2004, we can hope that this rift will soon be healed.
The cryonics community (and industry) is one of the oldest and most established modern scientific life extension movements. Many people of note in the wider community have some ties to it, and cryonicists can take some credit for driving the modern interest in developing nanomedicine based on molecular nanotechnology. You can read more about cryonics here at Fight Aging!
Health Enthusiasts and Advocates:
It can be a short jump from health advocate to healthy life extension advocate. Professionals like Dr. Mercola discuss ways to extend (or rather, not reduce) natural longevity through lifestyle and diet choices.
Hormone therapies do not have the scientific credibility of other older healthy life extension technologies, and studies are very divided on their use and usefulness. There is a sizeable group of for-profit entities who stand behind the use of hormone therapies, however.
Why is libertarianism the only political philosophy noted here? The historical association between libertarianism, transhumanism, futurism and cryonics is a strong one and worth noting. You'll find an even distribution of political orientations throughout the healthy life extension community, but there are a lot of libertarian cryonics supporters, futurists and transhumanists. This is in part a function of the history and personalities of these movements, but it also comes with the territory.
Little serious research into enhancing healthy longevity takes place in comparison to aging research - which seeks only to understand the aging process, not change it. Aging research is itself underfunded in comparison to research into curing conditions like cancer. A good example of a modern longevity research effort is Aubrey de Grey's SENS project.
Longevity Science Advocacy:
Fight Aging! is, I like to think, a good example of this part of the community. I support a rapid advance in all fields of science likely to extend the healthy human life span. The SENS Foundation, Methuselah Foundation and Immortality Institute are other noteworthy longevity research advocacy groups.
Longevity Science Business Ventures:
The newer companies working on the science of calorie restriction, regenerative medicine, the biochemistry of aging, and similar high tech goals. These are startups, some very well funded, founded over the past decade.
Mainstream Doctors and General Practitioners:
Most doctors in general practice tend to be a few years behind the curve, so it's a good idea to make sure that your doctor understands healthy life extension. The Life Extension Foundation can help you with that.
Nanomedicine is still in the conceptual stages, although many new diagnostic tools are expected from the nanotechnology field within the next five years. Proponents of nanomedicine based on molecular nanotechnology explicitly aim at methods of greatly extending the healthy human life span. Robert Freitas' book "Nanomedicine" is a good starting point if you want to learn more, as is the full version of "Death is an Outrage."
Old Anti-Aging Business Ventures:
The Life Extension Foundation and A4M fall into this category. These businesses tend to be rooted in the supplement, hormone and older medical technology base, although some do fund modern research. The Life Extension Foundation founders are also deeply involved in the growth of the cryonics industry.
Patient Advocate Groups:
These groups support efforts to cure particular medical conditions, and many have thrown their weight behind fundamental regenerative medicine research as well. Good examples of the type are the Coalition for the Advancement of Medical Research and the Christopher Reeve Paralysis Foundation. Christopher Reeve was an outspoken advocate for stem cell research and therapeutic cloning, and his work continues to benefit the healthy life extension community.
Regenerative Medicine and Tissue Engineering:
Efforts in this rapidly growing field are likely to lead to the first wave of real healthy life extension therapies: medical technologies that can repair some of the damage caused by aging and degenerative age-related conditions.
Related Advanced Medical Research:
No research happens in a vacuum, and amazing advances in any one field rest on breakthroughs in others. Progress in bioinformatics in particular is driving the speed of modern research into biochemical mechanisms of aging, disease, cancer and the natural workings of the body.
The intersection of sports medicine and healthy life extension is an interesting one, but it makes sense if you stop to think about it. Both aim at extending and improving natural capabilities. A4M is a good example of intersections in this part of the diagram.
Supporters, Buyers, Sellers and Advocates of Supplements, Vitamins, etc:
Modest supplementation is definitely a good thing. That said, there is no end to how far you can go in the quest to optimize your health, and no end to the businesses that will help you or the discussion groups devoted to the topic. It's very much like tinkering with your automobile: people put significant time and energy into improving their supplement intakes by a tiny amount. But will you ever really know if you're getting that last 10% of possible health and longevity? I think it is better to focus your efforts on helping regenerative medicine arrive more quickly.
Transhumanists and Other Futurists:
Transhumanism and futurists have long had a close association with healthy life extension. Aging and death are limits to be challenged and overcome, just as we humans have overcome many past limits with advancing technology. Ray Kurzweil and many of his contemporaries are strong supporters of efforts to extend the healthy human life span.
The Strategies for Engineered Negligible Senescence, or SENS, is the name given to a research and advocacy program that aims to develop a cure for aging. This will take the form of a package of therapies and biotechnologies capable of repairing the known forms of cellular and molecular damage that accumulate in our bodies with age, and are thus most likely the root causes of aging. This may sound ambitious indeed, but read on: you'll find that the research community is closer to being able to realize this goal than you might imagine.
An Introduction to SENS
At present the Strategies for Engineered Negligible Senescence (SENS) are a synthesis of the following items: a scientific research program carried out under the auspices of the SENS Research Foundation and involving a number of laboratories and researchers around the world; a wide range of existing life science knowledge produced over the past decades; a call to action for the public and the scientific community; and the SENS proposals first put forward by biomedical gerontologist Aubrey de Grey.
SENS is of great importance for those of us who are interested in living much longer, healthier lives. The crucial, central point of the SENS vision is that scientists already know more than enough to be working on the development of therapies that can reverse the root causes of age-related degeneration. There is no reason or need to delay this work. SENS provides a roadmap for the near future of rejuvenation research, as well as ethical and utilitarian arguments for moving to defeat age-related degeneration as rapidly as possible. The SENS initiative has been growing over the past decade and now has the support of prominent philanthropists and life scientists.
If you'd like a complete description of SENS from top to bottom, Aubrey de Grey and Michael Rae have written Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. In that book they explain, as best we know based on the biotechnology and scientific knowledge of today, how we can band together, build a mighty research infrastructure, and greatly extend our healthy life spans soon enough to matter. Ending Aging is perhaps the best introduction to the science and rationale of SENS, and is highly recommended.
The Science of SENS
It is proposed that there are most likely only seven categories of biological process that lead to degenerative aging and age-related disease, all of which have been known for at least twenty years. That no new categories have been discovered since the late 1980s - over a time of great progress in all fields of biology and medicine - strongly suggests that there are no other significant causes of age-related degeneration and disease. Scientists can already describe potential therapies that could address each of these processes. The basic tools required for these therapies have in many cases already been demonstrated in the laboratory or in trials for more limited uses. A list follows:
1) Some tissues lose cells with advancing age, like the heart and areas of the brain. Stem cell research and regenerative medicine are already providing very promising answers to degeneration through cell loss.
2) We must eliminate the telomere-related mechanisms that lead to cancer. One possibility is to selectively modifying our telomere elongation genes by using targeted gene therapies.
3) Mitochondrial DNA is outside the cellular nucleus and accumulates damage with age that impairs its critical functions. The SENS approach is to use gene therapy to copy mitochondrial DNA into the cellular nucleus. There are other strategies for manipulating and repairing damaged mitochondrial DNA in situ some first demonstrated as early as 2005.
4) Some of the proteins outside our cells, such as those vital to artery walls and skin elasticity, are created early in our life and never recycled or recycled very slowly. These long-lived proteins are susceptible to chemical reactions that degrade their effectiveness. Scientists can search for suitable enzymes or compounds to break down problem proteins that the body cannot handle.
5) Certain classes of senescent cell accumulate where they are not wanted, such as in the joints. We could in principle use immune therapies to tailor our immune systems to destroy cells as they become senescent and thus prevent any related problems.
6) As we age, junk material known as amyloid accumulates outside cells. Immune therapies (vaccines) are currently under development for Alzheimer's, a condition featuring prominent amyloid plaques, and similar efforts could be applied to other classes of extracellular junk material.
7) Junk material builds up within non-dividing, long-life span cells, impairing functions and causing damage. The biochemistry of this junk is fairly well understood; the problem lies in developing a therapy to break down the unwanted material. The SENS approach here is to search for suitable non-toxic microbial enzymes in soil bacteria that could be safely introduced into human cells.
The State of Progress in SENS
Modest philanthropic funding for SENS research commenced in 2005 under the administration of the Methuselah Foundation, and the total funds raised grew to more than $7 million by 2009 - and kept going. By 2010, the SENS Research Foundation's yearly expenditures topped $1 million, in 2012 more than $3 million, and as of 2015 the annual budget of the SENS Research Foundation is about $5 million, a tenth of that of comparable research institutions in the mainstream of aging science such as the Buck Institute. The pace of progress on work that is funded only within the SENS research community is consequently slow in comparison, and one of the principle aims of the SENS Research Foundation staff is to ensure that they are not the only group coordinating and funding this research. There is far too much to accomplish for any one organization.
The SENS research portfolio incorporates some lines of work that are well funded and widely supported, however. In the stem cell research community many groups are making progress on understanding why stem cell activity declines with age and how to safely intervene in this process. Additionally, similarly broadly supported work on the replacement of stem cells and enhancement of regeneration in aged and damaged tissue is taking place. Since the majority of potential regenerative treatments emerging from stem cell research target age-related disease, scientists must solve the problems of stem cell aging in order for therapies to work effectively. The cancer research community is as well funded and energetic as the stem cell field, and here too there are lines of work that will lead to robust treatments for many different types of cancer in time. The Alzheimer's research community is also heavily funded, and in this case the most interesting work from a SENS perspective is the development of immunotherapies to clear amyloid from the brain. This has proven to be a challenging goal, with only failures so far at the clinical trial stage despite the time and money invested, but at the end of the day the outcome will be a general technology platform that can be turned to address other forms of amyloid in the body, and thus remove their contributions to degenerative aging.
Concrete progress is also occurring in some of the poorly funded areas of SENS rejuvenation biotechnologies, albeit at a far slower pace. In 2014 and 2015 researchers produced technology demonstrations for senescent cell clearance treatments, showing benefits to health in normal aged laboratory mice, and received considerable attention from the media as a result. A startup company was funded based on one of these technologies. It may or may not succeed, but the point is that this particular line of work is now expanding beyond the bounds of research groups funded by the SENS Research Foundation, and attracting a growing level of attention. There is increasing interest in the scientific community in this strategy for treating aging. Also in 2015 another startup was founded, Human Rejuvenation Technologies, with the aim of producing a therapy for atherosclerosis based on the results of SENS Research Foundation programs for clearance of intracellular aggregates. Further, methods of repairing mitochondrial DNA damage funded in part by the SENS Research Foundation have moved beyond the laboratory and have been under commercial development since 2013 for narrow uses in the treatment of inherited mitochondrial disorders such as Leber's hereditary optic neuropathy - but the resulting technologies will be applicable to aging.
Unfortunately other lines of SENS research have yet to reach this point of critical mass: for example clearance of cross-links does see some interest and research in the broader scientific community, but has not yet had its breakthrough moment.
The Role of the Rest of the Research Community
It is not unreasonable to expect the broader research community - motivated as it is to seek cures for specific named diseases - to slowly fill in the gaps in SENS as time moves on and as the path ahead is better illuminated. For example, Alzheimer's researchers are working on immune therapies to address both amyloid plaques and other forms of junk material suspected to cause neurodegeneration. Further, some groups with no direct affiliation to the SENS Research Foundation are attempting to develop repair techniques for damaged mitochondrial DNA, build cross-link breaking drugs, or clear less well known forms of amyloid in order to treat certain classes of age-related illness.
It is also the case that regenerative medicine is a large and well funded field largely focused on using existing biological mechanisms to build new, replacement tissue for the body. Other researchers are also investigating the manipulation of telomeres in order to prevent or treat cancer. Yet more groups are working on compounds to break down accumulated biochemical junk outside cells.
Making gains in SENS research by way of unrelated bits and pieces is likely to be a slow path for progress towards meaningful extension of healthy life, however. Curing any one age-related condition is a wonderful thing for sufferers, but it will not increase healthy life span for anyone else - nor will it lead directly to therapies that can extend life without further investment and work. All of SENS must be implemented in order to reliably extend healthy life for all of us, and thus there must be at least some portion of the research community working directly and deliberately towards a complete implementation of the SENS vision.
The Ethics of a Cure for Aging
In many ways the hardest part of the path ahead for supporters of healthy life extension lies in convincing people that SENS and similar scientific projects should be funded in the first place. The science is much more certain than the public support. This is a strange state of affairs when you stop to look at it. As Aubrey de Grey notes: "Aging really is barbaric. It shouldn't be allowed. I don't need an ethical argument. I don't need any argument. It's visceral. To let people die is bad. I work to cure aging, and I think you should too, because I feel that saving lives is the most valuable thing anyone can spend their time doing, and since over 100,000 people die every single day of causes that young people essentially never die of, you'll save more lives by helping to cure aging than in any other way."
Many people demonstrate a certain willful blindness to the death and suffering caused by aging, a blindness that is not present for age-related disease like cancer or Alzheimer's. Yet if you support medical research to cure disease, prevent death, and relieve suffering, then you should also support medical research to prevent and rejuvenate age-related degeneration. How is suffering and death caused by the general deterioration of aging any different from suffering and death caused by a specific age-related condition we understand and have given a name?
We should all do our part to help speed development of therapies for aging. It is the right thing to do.
Last updated: September 28th 2015.
The first Immortality Institute book of essays is now available at Amazon.com. It includes work by scientists like Michael Rose, Michael West, Robert Freitas, Aubrey de Grey, Marvin Minsky and João Pedro de Magalhães, writing alongside futurists and transhumanists like Ray Kurzweil, Max More and Mike Treder. How can we best work towards defeating the aging process and preventing all age-related disease? How rapidly could we attain these goals and how much would it cost? What would an ageless future society look like, and what technologies would be required to support it? How does this all fit in with current trends in accelerating technological development? You can read more about the book and these authors at the Immortality Institute website.