CNN devotes an article to the Mprize for anti-aging research today. To quote Steven Spindler, the current Mprize record holder, "we need to convince policy makers that finding the causes of aging is a reasonable thing to do. Some people still consider extending life span as quackery, but like every other field of medicine, the more we know the more we are able to reverse things and extend life span, not just the bad years - but by slowing down the aging process." The Mprize is funded by people like you and I who want to see more and faster progress towards significant healthy life extension therapies - it is a popular prize in the best sense of the term. Join in and make a difference!
Now that calorie restriction is becoming a much more popular - and well funded - field of research, we are starting to see a range of basic, thoughtful tests as well as forward-looking work on genetics, biochemical mechanisms and calorie restriction mimetic drugs. Betterhumans covers some of the latest results in flies:
Cutting fat and protein extends fly lifespan without cutting calories, providing further insight into the effects of diet on longevity.
Researchers varied the nutrients in the fly's standard lab diet of yeast and sugar. Both yeast (which contributes protein and fat) and sugar (carbohydrates) have the same calories per gram, allowing the researchers to adjust nutrient composition without affecting the calorie count. They found that reducing both nutrients increased the flies' life span, but cutting out the yeast had nearly as great an effect. Flies on a calorie-restricted diet lived 82% longer than controls, flies on the yeast-restricted diet had a 65% gain and flies on a sugar-restricted diet had just about a 9% gain.
The original paper can be read in full at PLoS Biology. The obvious next step is to try something similar in mammals (such as mice) and see what happens; I will be interested to see the biochemical explanations for these results, bearing in mind the information that researchers have uncovered to date.
The work of the late Roy Walford is recalled at the open access journal Immunity & Aging: "Roy Walford died on April 27, 2004, at the age of 79. His contributions to gerontological research in such diverse areas as caloric restriction, genetics of lifespan, immunosenescence, DNA repair and replicative senescence were truly remarkable in their depth and innovation. Significantly, most of the areas that he pioneered during his illustrious research career remain the 'hot' areas of current gerontological research. ... it is highly fitting, therefore, to remember him on the anniversary of his death by briefly reviewing the contributions of Roy Walford to this important facet of gerontology. Indeed, it was Roy who actually first coined the commonly used term 'immunosenescence'".
I have to admit, I find it very annoying to see otherwise sensible people throwing around terms like "nut" and "fringe enthusiast" on the basis of the briefest aquaintance with facts and background to describe biogerontologist Aubrey de Grey. The man is a scientist. He works in science. He writes papers, organizes conferences, chairs a journal, is an advisor to any number of scientific organizations. If his chosen field - a small, neglected, underfunded field repleat with situational oddities and personality clashes - happened to be anything other than rejuvenation and anti-aging research, you most certainly wouldn't be seeing any of this nonsense. Does the small community of biologists who spend their time scraping together conferences and funding for the study of rare frogs in obscure parts of the world get this much disrespect?
I really find it hard to believe that my modest acquaintance with the inside of the scientific sausage-making process renders me somehow privileged when it comes to understanding the way in which these things work. It's not rocket science! The slow fight over the introduction of a new paradigm is just human nature; one of the hardest aspects of working within the scientific community is getting the old guard to debate your new ideas in public. I experienced that in person in a completely different field, but is this concept really so hard to understand?
The International Herald-Tribune profiles Korean scientist Hwang Woo Suk and the advances he and his team have achieved. "On one hand, you have 15 micrometers of skin cells, on the other a patient who has suffered from an incurable disease. Maybe this 15 micrometers of skin cell can relieve and save the life of a human being next to me, someone who has suffered for 50 years or must suffer for 50 years. Of the two, which do you think is ethically reasonable to save?" Peering past the the light and noise of the South Korean government publicity and myth-making machine at work, it is still clear that promising medical science is taking place; we can hope that the newly developed techniques will spread rapidly as promised.
The latest newsletter from the American Aging Association (AGE) includes a PDF format discussion on the state of the evolutionary biological theory of aging. It "predicts a polygenic basis for aging and the likelihood that multiple mechanisms are involved. Then how, many would ask, can the theory be reconciled with the mounting evidence that single gene mutations in worms, flies and mice can lead to enhanced life spans? And how to reconcile the fact that a single environmental intervention - caloric restriction - can enhance the life spans of so many species?" Aubrey de Grey and Leonid Gavrilov are amongst those offering opinions, making it well worth reading. As a reminder, the 34th AGE annual meeting starts this week in California.
The early registration and abstract submission deadlines for the second conference on Strategies for Engineered Negligible Senescence (SENS 2) are on June 15th, 2005. "The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research and the Methuselah Mouse Prize), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - reverse - those changes, rather than merely to slow down their further accumulation. This year's SENS Lecture, provisionally entitled 'Stem cells, SCNT and the rejuvenation imperative', will be given by Dr. Michael West, CEO of Advanced Cell Technology."
FuturePundit provides more commentary on recent research into the consequences of age-related damage to cellular mitochondria. "Failures in mitochondria due to aging are suspected of causing atherosclerosis and heart disease ... Mentally I file this under 'Totally Unsurprising'. Mitochondria have their own DNA for some of their proteins. Some gerontologists (e.g. Aubrey de Grey) theorize that the mitochondrial DNA (mtDNA) acts as a sort of Achilles Heel in cellular metabolism and cellular aging. Very reactive chemical compounds get generated in mitochondria by breaking down sugar and some of those compounds occasionally break loose and fly into the mtDNA causing damage. So mtDNA might accumulate damage at a much faster rate than DNA in the nucleus."
Aubrey de Grey's latest thoughts on WILT - Whole-body Interdiction of Lengthening of Telomeres - will appear in Frontiers in Bioscience later this year. Those who are new to the Strategies for Engineered Negligible Senescence (SENS) proposals may want to take a look, although only the abstract and list of contents are online as of the moment:
The intrinsic genetic instability of cancer cells makes age-related cancers more difficult to postpone or treat than any other age-related disease. Any treatment that a cancer can resist by activating or inactivating specific genes is unlikely to succeed over the long term, because pre-existing cancer cells with the necessary gene expression pattern will withstand the therapy and proliferate. "Whole-body Interdiction of Lengthening of Telomeres" (WILT) is a proposal to pre-empt this problem by deleting from as many cells as possible, the genes required for telomere elongation. Cancers lacking these genes can never reach a life-threatening stage by altering gene expression, only by acquiring new genes, which is far more unlikely. Continuously-renewing tissues can be maintained by periodic reseeding with telomere elongation-incompetent stem cells that have had their telomeres lengthened in vitro with exogenous telomerase. Here, I describe why WILT might prove to be an exceptionally powerful anti-cancer modality.
Both InfoAging and Wikipedia are good places to start for basic information on telomeres and why you should know more about them in the context of healthy life extension. You'll find more on the whys and wherefores of WILT and age-related cancer at the SENS website, and even more discussion and argument in the Immortality Institute SENS forum. That should keep you reading for a while...
UPDATE: The full paper in PDF format is now available at the SENS website.
The Financial Times follows the party line for mainstream media articles on transhumanism and transhumanist enthusiasm for the technologies of healthy life extension. The article presents a short list of amazing achievements and improvements to the human condition that technology - and medical technology in particular - has already accomplished, followed by another list of amazing advances yet to come ... and then dives off the cliff into why this is all a terrible, terrible thing and will never work to boot. I note numerous references to the uniform mortality rate amongst past advocates of radical life extension - but looking at the past is a very bad way to predict the future, that much is certain. A final question: what is worse, forcing billions of people to suffer and die, or making a few hundred self-righteous bioethicists uncomfortable?
An article at Newsday.com expects the Connecticut legislature to follow through with a plan for public funding of stem cell research: "On a 31-3 vote, the Senate approved spending $100 million over 10 years to fund the research, which scientists believe could hold the key to curing diseases such as juvenile diabetes and Alzheimer's. Eighty percent of the funding would come from the state's share of the national settlement with tobacco companies. ... The bill now goes to the state House, where it has the support of the speaker. Republican Gov. M. Jodi Rell applauded the Senate action. 'I would be proud to sign the bill when it reaches my desk.'" It is plausible that present battles over much larger sums of money will make it easier to pass more modest funding legislation.
I feel it's worth noting that Brian Delaney and Lisa Walford's new book on calorie restriction is now shipping; you can order from Amazon and expect a near-future delivery. It has a weighty title: "The Longevity Diet: Discover Calorie Restriction - the Only Proven Way to Slow the Aging Process and Maintain Peak Vitality" - following the old adage about the best way to sell from the bookstore shelf, I suspect.
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 to extend your healthy years.
Here's the concept: eat fewer calories and choose foods more carefully. This will reallocate how your metabolism uses its resources to convert food into energy; in other words, what goes in will be used more efficiently. You 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.
Brian Delaney and Lisa Walford, 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.
If any of you folks in the community have your hands on a copy and want to let me know what you think, go right on ahead. More publicity for calorie restriction and the Calorie Restriction Society is a good thing in my view - CR is a gateway concept that can lead a wide range of people to think seriously about radical life extension and advanced medicine for longer, healthier lives.
During a panel on the future of nano-biotechnology, Alan Russell, head of regenerative medicine at the University of Pittsburg, described progress in moving from treating symptoms to generating cures and regenerating tissues as a result of the convergence of nanotechnology and biology. "Every tissue from head to toe is being regenerated somewhere across the planet," Russell said. Corneal epithelium are being grown in dishes at one temperature and then cooled and peeled off and placed on an eye. Three patients in the U.S. have received whole cultured bladders grown using nano-biology techniques. A uterus can be grown outside the body in animal tests, placed inside the body and subsequently produce babies. He predicted that within the next five years, spinal cord injuries will be treated with stem cells and some of the paralyzing effects reversed. In South America, stem cell therapy is used to eliminate disease in failing hearts. U.S. trails are starting next week, Russell said. The Department of Defense has allocated $20 million to study whole limb generation. "If a newt can do it, why not we," Russell said. However, limb regeneration is more than five years out.
"Nanotechnology" in this business-oriented context should be taken to mean nanoscale engineering rather than more futuristic visions (such as molecular manufacturing). The first wave of nanotechnology is an straightforward advance in materials science and the ability to reliably manipulate ever smaller objects - such as cells and their subcomponents. The above quote is very enthusiastic on the topic of regenerative medicine, but is not too much of an exaggeration - a great deal of very interesting work is currently taking place at the cutting edge of medical research. We'll have to wait a decade to see what crystallizes out of the mix in terms of therapies and widespread uses, but it all looks very promising from where I stand.
RedNova reports on the goals of a new Irish bioengineering center: "Research on mechano-biology will be used for tissue engineering or muscle skeletal tissue. For example when you get degeneration of cartilage, such as you get with arthritis, we can grow tissue outside the body and put it in to replace defects inside the body ... There is another disease where the bond underneath the cartilage begins to stiffen. When the bond underneath the cartilage gets stiffer, the cartilage then is more highly stressed because it is sitting at the top of a stiffer bond, and there is the start of the process of degeneration of the cartilage. Many musculature diseases begin with problems with the bond tissue." Developing regenerative medicine for all age-related conditions is going to take a vast amount of work.
SFGate.com excerpts a profile of Cynthia Kenyon from David E. Duncan's latest book: "I think that [immortality] might be possible. I'll tell you why. You can think about the life span of a cell being the integral of two vectors in a sense, the force of destruction and the force of prevention, maintenance and repair. In most animals the force of destruction has still got the edge. But why not bump up the genes just a little bit, the maintenance genes. All you have to do is have the maintenance level a little higher. It doesn't have to be much higher. It just has to be a little higher, so that it counterbalances the force of destruction. And don't forget, the germ lineage is immortal. So it's possible at least in principle" Interesting in light of Kenyon's recent reluctance to critique Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS).
Since we've already touched on the topic of transhumanism and Ramez Naam, I should note that More Than Human is reviewed at Betterhumans today. "Rather than just defending human enhancement, he delineates why we should embrace it, and suggests approaches for doing so responsibly. In regards to life extension, for example, Naam points out that older people are more likely to vote, less likely to commit violent crimes and less likely to prefer militaristic solutions. So why wouldn't we want more older, wiser people in society?" A little too indirect for me - we should embrace healthy life extension because it will greatly reduce suffering and death. Very simple. You can read an excerpt from More Than Human focused on healthy life extension and population growth here at the Longevity Meme.
A long three-way interview with James Hughes, Ramez Naam (author of More Than Human) and Joel Garreau is posted over at WorldChanging: the future of healthy life extension and advancing medical technology is one of the many topics addressed. Some good points are made along the way: "I also don't think that there's any useful distinction between therapy and enhancement although many people will persist in making it. My favorite example is that anti-aging medicine will stop an awful lot of diseases. I don't see how you can distinguish in that case between saying well this is also a prophylactic against cancer, and saying that it will extend my life a couple tens of decades."
The reliability-engineering approach to understanding aging is based on ideas, methods, and models borrowed from reliability theory. Developed in the late 1950s to describe the failure and aging of complex electrical and electronic equipment, reliability theory has been greatly improved over the last several decades. It allows researchers to predict how a system with a specified architecture and level of reliability of the constituent parts will fail over time. But the theory is so general in scope that it can be applied to understanding aging in living organisms as well.
In reliability theory, aging is defined through the increased risk of failure. More precisely, something ages if it is more likely to fall apart, or die, tomorrow than today. If the risk of failure does not increase as time passes, then there is no aging.
Reliability theory is, like evolutionary considerations of aging, a "why" theory rather than a "how" theory. It is useful as a reference point and foundation when thinking about how to address the aging process via medical science, and fits well with Aubrey de Grey's Strategies for Engineered Negligible Senescence. You can download the PowerPoint materials at Leonid Gavrilov's website.
From Nature, information on yet another part of age-related degeneration that can be blamed on accumulated damage to mitochondria. "As the cells in blood-vessel walls grow old, their energy-generating machinery begins to leak, says the team. This releases reactive molecules into the vessels, triggering a chain of reactions that ultimately clogs up arteries and increases the risk of having a heart attack ... They speculate that an increased flow of reactive oxygen damages the blood vessel's walls. The body then mounts an immune response to repair this damage, and scientists have already established that cells trying to fix arterial damage can create problems." Fixing mitochrondial damage is one of the proposed Strategies for Engineered Negligible Senescence.
An interesting article from the New Scientist looks at the work of Yuri Verlinsky in Chicago, who "claims to have produced patient-matched embryonic stem cells without resorting to therapeutic cloning. ... Verlinsky says he has already created 10 embryonic stem cell (ESC) lines using his new 'stembrid' technique. Unlike therapeutic cloning, it uses existing ESCs instead of human eggs, and so would be much cheaper and easier. ... other experts say Verlinsky must do a lot more work to prove his claim." The ethical discussion is something of a red herring; the real item of note is that multiple research groups are working on different paths to the same goal. That is a good sign in any field of medical science.
US stem cell politics casts its pall across the land and requires me to write on the topic rather than on something more constructive and directly related to longevity research. Let me start by saying that, in my cynical, libertarian eyes, little of use was accomplished by politicians yesterday - as on any other day. Sure, the US House of Representatives passed a few bills on stem cell research amidst much posturing and grandstanding:
The US House of Representatives has voted to increase government funding for embryonic stem cell research. The vote sets up a confrontation with President Bush, who has vowed to veto the bill if it passes the Senate. The bill was passed by 238-194 votes - short of the two-thirds majority required to override Mr Bush's veto.
The senate has sat on stem cell legislation of varying sorts - good, bad and ugly - without a vote for two years now; it is quite possible there will be no further vote on this latest legislation. Even if there was, and even if the President declines to follow through with the threat of a veto, will this bill mitigate or stop threatened anti-research legislation that has scared away private funding for years in the US? Would it prevent politicians and other parasites from holding back research, pinning down the engines of progress beneath a mountain of regulation and unnecessary costs?
One can suppose that a degree of my cynicism on this issue is triggered by policitians yet again donning the robe of savior to "fix" a problem of their own creation. Without overreaching politicians and an overpowered state, we would simply have freedom of research and rapid progress. Past history should teach us that true progress is made despite politics, not because of it.
Here is an interesting comparison: look at the size and funding of the Korean team that made two noteworthy breakthroughs in embryonic stem cell research and therapeutic cloning in the past two years:
... their research got less than 200,000 US dollars a year in funds mainly from the government.
Two years is around the length of time that Advanced Cell Technology - a formerly high profile private company and one of the original forerunners in stem cell research - has been languishing for lack of private investment as a result of the hostile US political environment. From October 2004:
Due to a dearth of funding, Lanza said his company has been unable to follow up on promising results in animals and carry out experiments that could lead to life-saving therapies for humans. The financial situation is so dire, the company has at times been unable to afford basic office supplies."
Another interesting comparison: the concrete philanthropic donation of $50 million to stem cell research - including embryonic research and therapeutic cloning - from the Starr Foundation was announced this week. A search for "Starr Foundation" on Google News will net you a bare 22 hits as of the time of writing. Compare that with the barrels of ink spilled on the worthless posturing of politicians yesterday ... the denizens of our society appear to have serious problems relating to values, what is important and a general grasp on reality.
DrugResearcher.com reports on a survey of the scope of current cancer research: 399 new therapies and medicines are currently in development. Most will no doubt flounder in one way or another (the FDA proving to be a very effective barrier to medical innovation), but this is still an impressive breadth of work. The cancer research community, from activists to funders to scientists, is something that we in the healthy life extension community should seek to emulate. The pathway for medical activism leading to growth of research and large-scale funding is proven; it's been done for cancer and diabetes and is in progress for Alzheimer's disease. We can do this for serious anti-aging, rejuvenative medicine - it's just a matter of work.
Sadly, his seems to be a week for politics and obstruction rather than research. SFGate.com looks at what is happening to the California Institute for Regenerative Medicine: "Leaders of California's Proposition 71 stem cell research program launched a new campaign Monday against state legislation they say threatens to kill the $3 billion program before the first grants are issued. ... Both those developments underscore just how unsettled public policy has become as scientists try to fulfill the medical promise of regenerative medicine against a backdrop of ethical objections and funding uncertainties." Massive public funding makes for massive waste as groups fight slow legislative battles. In my humble opinion, it would be far more effective to eject government from research and regulation, letting scientists make rapid progress with philanthropic and private funding.
As I noted in an update to a recent post, Cynthia Kenyon backed down from agreeing to review Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS) for Technology Review. All within a few days of editor Jason Pontin announcing it too; one has to wonder about the timing and thought processes there. This is, sadly, par for the course; as Aubrey has remarked in the past, one of the hardest parts for him is to get other scientists to debate on the merits of his proposals in public. There is still tremendous stigma attached to anti-aging and healthy life extension in the gerontology community, counterintuitive as that might be. Imagine a cancer research community that did nothing but examine the biochemistry of cancer, that made no effort to seek cures, and indeed actively discouraged attempts to implement therapies - sounds ridiculous, right? Yet that is exactly the state of affairs we are faced with within gerontology. There is no shortage of calls for more funding for aging research, for work to understand the aging process, but only the sound of crickets (and forward-looking folks like Aubrey de Grey) when it comes to working towards rejuvenative therapies for the aging process.
I seem to recall someone suggesting that we place a bounty on a published, peer-reviewed scientific critique of SENS from an A-list life scientist. This is sounding like a better idea as time goes by, but it looks like such a bounty would have to be somewhat larger than whatever the going rate for articles is at the Technology Review...
Another point to consider: so long as Jason Pontin is working towards this goal, he's doing good work for the cause of healthy life extension activism, even though his ultimate intentions are less than helpful and his his views on the nature of science are very wrong:
My objections to de Grey's prescriptions were pseudo-philosphical: I felt de Grey wasn't doing science so much as religion. This feeling sprang from scientific skepticism: no working biogerontologist to whom I spoke thought much of de Grey's theorizing. All noted that he had never worked a "bench"--that is, he performs no experiments.
By this standard, my years in theoretical astrophysics count for nothing - and half the scientists in the world are doing pretty much nothing as well. It's just plain wrong to equate non-lab work with non-science.
Against a backdrop of far too much politicking, the Starr Foundation has committed to $50 million in funding for stem cell research in New York. "The Tri-Institutional Stem Cell Initiative will seek to decipher the molecular codes ultimately responsible for human cellular diversity and eventually use this understanding to design cell-based therapies. ... greater understanding of their capacity and of how to direct their activity allows scientists considerable potential to develop new regenerative treatments that would deploy the body's own ability for growth and repair against a range of conditions such as Parkinson's disease, diabetes, spinal cord injury, stroke, burns, heart disease, cancer, and arthritis."
The Foresight Nanotechnology Challenges are a high level roadmap for improving the human condition with advanced nanotechnology. As a part of the challenge to increase health and longevity through the application of nanomedicine, biogerontologist Aubrey de Grey provides the first and second expert opinions. "The postponement of aging is likely to follow a trajectory similar to most technologies for which there is widespread enthusiasm: after an indeterminate period in pursuit of the initial breakthrough, improvements to the technology in terms of cost, convenience and efficacy will occur rapidly. ... effective life-extension therapies will [repair age-related damage, rather than merely slowing down its accumulation, thus] most of the beneficiaries of the early life-extension therapies will survive long enough to benefit from subsequent, more effective ones."
Frank from Anti-Aging Medicine & Science sat in on the Immortality Institute's latest online chat session, this time with S. Jay Olshansky as a guest. He comments:
I came away from the chat with the feeling that Professor Olshansky has been unfairly villanized by some in the anti-aging community. Folks, he's on our side. While he doesn't see radical life extension happening any time soon, he believes that anti-aging work should be done and he is a supporter of the Methuselah Mouse Prize.
I've probably done my share of unfair villanizing in the past, but in my defense I should note that Olshansky has changed his public position on healthy life extension over time. The positive spin to put to that is that Aubrey de Grey is succeeding in his fight to bring the scientific community around to his way of thinking about things. The sort of criticisms I have applied in the past to Olshansky are still true for many other prominent folks in the research community; people whose public and private stances on healthy life extension research are quite different, or who refuse to address the issue publicly in a substantiative way. Progress at this early stage is a matter of broading and expanding the discussion as much as anything else.
UPDATE: You can find the chat log in the discussion thread for the chat session. Go read it - interesting stuff.
[17:01] <BJKlein> Jay, so why are you picking on us?
[17:01] <JayO> because I want you to succeed.
Wouldn't it be good to be able to put the spare processing power of your computer to use in advancing medical science? You can! Folding@Home is a distributed computing project from Stanford University that relies on the contribution of millions of hours of spare computing time from people like you and I. This processor power is used to solve the hardest, most pressing problems in protein biochemistry, speeding up the search for therapies and cures for degenerative conditions of aging. Currently, Alzheimer's disease is one of those at the head of the list. The Longevity Meme Folding@Home team (number 32461) is growing and moving up in the ranks - join the team and compete to advance medical science!
I spent a little time cleaning up the Longevity Meme website content yesterday, focusing on the Take Action! activism section. Maintaining a website is a little like maintaining a mansion - there are always too many rooms to clean and too little time to do the work. So you polish the areas that people look at most frequently and work on the rest as you can. Slick, relevant, useful content has a way of getting stale and dusty even with the best of future-proofing - and no-one wants to be perusing a stale, dusty website.
Having brought that area up to some semblance of respectability, the next project is to revamp the way in which I present the concepts of healthy life extension, regenerative medicine and anti-aging research (of the Strategies for Engineered Negligible Senescence (SENS) variety). Much of the introductory writing on the Longevity Meme was originally drafted prior to my association with Aubrey de Grey and the Mprize team, at a time when I was very much more focused on early battles over stem cell research. While the content has been tidied up and improved since then, the original thrust - that regenerative medicine is the best way forward for healthy life extension - has been rendered a little dated ... or at least, my present understanding of the possibilities of research has improved. One or the other. Clearly regenerative medicine is necessary and important, but SENS-like research forms an entirely separate program, and is a better path forward for near-term progress in radical life extension. This is a distinction that I need to make apparent and clear in the Longevity Meme introductory and supporting material.
The Times Online provides us with a fascinating look at the history of tissue engineering over the past decade, placing it the context of advancing understanding of stem cells and the young field of regenerative medicine. "Problem one: it takes a long time to grow something to order; and that may be time the patient doesn't have. Problem two: no one has yet cracked the problem of how to create a blood supply within larger tissue scaffolds. Problem three: there hasn't been enough money in it for commercial companies to drive the technology. ... scientists' attention has been diverted to creating tissue 'on site', rather than making body parts separately." The end goal is still to be able to replace age-damaged tissue with something as good as new.
(From Science Blog). A study in mice shows that delayed motherhood lowers the life span of children in mice: "Negative effects of late maternal age in women, such as abnormal numbers of chromosomes in their children, are well known. However, other potential negative effects on offspring from delayed motherhood have been only anecdotal. ... a team of reproductive biologists [presents data showing] that delayed motherhood in mice results in decreased life expectancy and reduced body weight of their offspring." This would seem to reinforce theories of aging based on accumulated genetic damage - if this damage in germ cells reduces the life span of your children, what is the same damage in other cells doing to your own body?
It seems I'm behind the times in my predictions of the near future of computing-driven biotechnology. Within a few weeks of my saying this:
Most currently real world experimental techniques - rather than just a select few - will become cheaper to carry out in simulation. Why spend millions keeping racks of mice when you can spend hundreds of thousands on reliable, tested software to do the same job - software that will become cheaper by an order of magnitude with each passing decade.
Wired pops up with an article on a working simulation of a mouse:
This month, the American Diabetes Association and biopharmaceutical company Entelos completed a virtual mouse that will be used to study cures for type 1 diabetes.
Running on a server, the non-obese diabetic virtual mouse will allow researchers to test the effects of new drugs on the virtual animal's cells, tissues, organs and physiological processes, according to Barry Sudbeck, Entelos' business development manager.
The virtual mouse can replace several stages of a pre-clinical drug trial, sparing the lives of hundreds of mice, Sudbeck said.
It's only a narrow application simulation, but I'm impressed; I hadn't thought that anyone was close to a viable product. This is the first step on the road towards vastly decreasing the time and cost of biotechnology development - not to mention making it a great deal more ethical. The ideal world is one in which we can speed ahead rapidly towards viable therapies without causing animal or human suffering in the necessary trials, studies and tests. Simulational experiments are the best road ahead.
The New Zealand Herald takes a long look at the politics and science of xenotransplantation, a a field of medicine that could produce therapies or even cures for diabetes and other age-related, degenerative conditions. "From these pigs, Living Cell is taking hormone-producing brain choroid plexus cells for experimental treatment of animals with brain injury, such as strokes, and brain disease, such as Huntington's. Even more promising are the pigs' insulin-producing, pancreatic islet cells, which are now being used for treating humans with diabetes." Unfortunately, xenotransplantation is in much the same place as embryonic stem cell research - held back by political restrictions, threats and FDA red tape.
From MSNBC, a fine example of anti-research politics in the US: "President Bush on Friday said he would veto legislation that would loosen restrictions on embryonic stem cell research and expressed concern about human [therapeutic] cloning research in South Korea. ... 'The president is opposed to that. That represents exactly what we're opposed to.'" This is exactly the sort of threatening environment - backed up by pending legislation to criminalize this research into cures for age-related conditions - that has scared away private investment and held back progress towards the full potential of regenerative medicine. The lesson is clear - if we want the liberty to lead longer, healthier lives, then we have to stand up and fight for it.
An interesting study is noted in a release from Newswise: "Obesity has long been known to result in early death, but researchers don't fully understand the process of aging at the cellular level. ... people with insulin resistance and weight gain also have prematurely shortened white blood cell telomeres - a widely recognized sign of aging. Telomeres are part of each chromosome and naturally become shorter over time as cells multiply and reproduce. ... We know that obesity and insulin resistance place a physical burden on the body, leading to inflammation, the production of more blood to feed the body, and oxidative stress, all of which are important factors in the biology of aging. It makes sense that we would see other signs of aging, like shortening of the white blood cell telomeres, as well."
Since I'm paying less attention to stem cell research at Fight Aging! these days, I feel it's worth reminding folks that other blogs - such as Today's Stem Cell Research and Hype and Hope - keep up a regular patter of postings. But onwards; recent good news from Korea may, if we're lucky, cause productive ripples in restrictive Western stem cell politics:
Robert Lanza of Advanced Cell Technology comments that the researchers "have demonstrated that therapeutic cloning can work in a medically useful way. Prior to this study, there was a question as to whether it was biologically possible. ... The answer is yes, it works. And they did it in a dramatic way - they used therapeutic cloning to derive stem cells that genetically matched patients who had real diseases that could be treated using this technology."
Ronald Bailey put out a piece for Tech Central Station in a very short period of time - it hits many of the points I was considering for this post:
The Korean researchers allowed the stem cells to differentiate into various cell types including skin, nerve, kidney and muscle cells. The stem cells produced by Hwang and his team are immunological matches for specific patients, and that means that if they were transplanted that they would not cause immune rejection. While this research is a tremendous breakthrough, the researchers hasten to point out that it is too early to consider actually transplanting the cells into patients. First, because some of the cloned stem cell lines carry the defective genes that led to diabetes and immunodeficiency disease. Second, because researchers still have to learn how to safely and stably transform stem cells into specific cell types, say, pancreatic islet cells to treat diabetes.
The House of Representatives has twice voted to criminalize precisely this research, proposing to toss therapeutic cloning researchers into prison for up to ten years and fine them one million dollars. In fact, if this effort to criminalize research on cloned human stem cells were to succeed, Americans who go abroad to seek cloned stem cell treatments, say, to cure their diabetes, could be jailed for up to ten years for illegally "importing" cloned stem cells. The Bush Administration was also pushing the United Nations to adopt a treaty to outlaw both cloning to produce transplants and reproductive cloning.
Some of the most promising research into cures for age-related conditions has been held back and underfunded for years in the US. But regular readers know this already; much of the recent news regarding stem cell research has been nothing but politics. It is a great pity that we live in a society that places so little value on individual responsibility, freedom and choice, especially in those areas of human endeavor where the most good could be accomplished. Centralization and socialization of medicine are terrible things; why do we allow the uninformed and unskilled to squander resources and hold life and death decisions over our heads?
The bottom line: politicized medical research is slower, less effective, less efficient medical research. The slower it goes, the more likely you are to suffer and die from an age-related condition that might otherwise have been cured. The slower it goes, the less likely we are to make serious progress towards a cure for the aging process itself. Politicians can do nothing but destroy and delay; they should leave well alone - let those who are willing to work put their talents, unhindered, towards creating longer, healthier lives for all.
Wired has more on the breakthrough from Korean scientists. Robert Lanza of Advanced Cell Technology comments that the researchers "have demonstrated that therapeutic cloning can work in a medically useful way. Prior to this study, there was a question as to whether it was biologically possible. ... The answer is yes, it works. And they did it in a dramatic way - they used therapeutic cloning to derive stem cells that genetically matched patients who had real diseases that could be treated using this technology." This is a large step closer to the ideal of regenerative medicine: "Now we're waiting for the clinical trials (using non-cloned embryonic stem cells) to show that they're safe. ... and then we can start thinking about perfect match cells that are 100 percent compatible with any disease you want to go for."
By the look of things, biogerontologist Cynthia Kenyon has agreed to a column for Technology Review in which she discusses Aubrey de Grey's Strategies for Engineered Negligible Senescence. From a blog entry by Jason Pontin:
In August, Cynthia Kenyon, a much-respected biogerontologist working at UCSF (she has significantly extended the lifespans of nematodes, amongst other successes), will answer de Grey in Technology Review's "By Invitation" column. What are the most important issues that Dr. Kenyon should address in her analysis of de Grey's ideas on human aging? Quick, write and tell me. Her deadline is approaching fast.
From my previous readings, I'm not actually all that sure where Cynthia Kenyon stands in terms of her view on the science. We all know where Pontin stands, and have castigated him appropriately for his ad hominem and unseemly attacks; I can't say that he seems to have learned his lesson yet, unfortunately.
Still, Pontin is asking for feedback for an article addressing substantiative scientific issues, so I think we should go and provide it - politely, please, even though he's being provocative as usual.
UPDATE: Apparently, she declined to do it after all:
I asked Dr. Kenyon if she would comment on de Grey's prescriptions almost three months ago; she agreed; and I announced her "By Invitation" column on this blog last week, asking readers what issues they would like her to address. But after a great deal of work, Dr. Kenyon very graciously told me she simply felt she couldn't do an "effective" job. I remain committed to finding a biologist who will criticize SENS: after Technology Review's profile of de Grey, Do You Want to Live Forever?, many of his admirers challenged me to have a working scientist say why de Grey's ideas were impractical--if they were impractical. So far, I have been unable to find one biogerontologist who felt comfortable writing about SENS--which is telling perhaps. But I shan't give up yet.
I wonder what's going on there behind the scenes?
Good news for regenerative medicine today: "South Korean scientists reported Thursday that they've generated the first human embryonic stem-cell lines carrying genes that match the DNA of patients suffering from disease or spinal-cord injury. The development [represents] a major step in the field of stem-cell research. The immediate impact is that researchers could soon study cells carrying specific variations of disease in the laboratory. ... What the study shows is that stem cells can be made that are specific to patients regardless of age or sex, and that these cells are identical genetic matches to the donor ... If they can be safely used in transplant, the promise for effective treatment - perhaps even cure - of devastating diseases and injuries comes within reach."
From donga.com, a Korean view of the future of regenerative medicine, medical nanotechnology, and healthy life extension: "The National Science and Technology Council (NSTC) has unveiled its projection ... In 2020, robots the size of a nanometer (one-billionth of a meter) will travel around blood vessels, clean them, and heal the damaged areas just like car technicians. Also, 'nano capsules' will circulate one's body, encountering pathogens such as viruses, and eradicate them by emitting drugs contained inside. ... Diseased organs in fatal conditions can be replaced by transplants, or 'alternative organs,' cultured from one's own stem cells. Once these prospects come true, we will usher in the era of healthy longevity in two decades."
Reading between the lines of a recent press release, Elixir Pharmaceuticals is positioning for competition with startup Sirtris Pharmaceuticals. Both companies are aiming at new therapies based on an understanding of the biochemistry and genetics of calorie restriction: "Sirtuins are related to Sir2, a gene identified in yeast that is conserved across species and implicated in the control of lifespan, metabolism, resistance to stress and other cellular regulatory pathways. Modulators of this enzyme class may provide important therapeutic agents for metabolic diseases such as diabetes and obesity, as well as HIV and cancer. ... Elixir has a comprehensive patent estate related to the sirtuins, including novel compositions and their potential application to disease treatment and longevity."
The M could stand for many things - like a million dollars, the prize money in its pot, or even medicine, the field of science it hopes to revolutionize. But it stands for Methuselah, the biblical character whose name is synonymous with longevity. The prize, set up by University of Cambridge biogerontologist Aubrey de Grey, will go to the scientific team that successfully extends the life or reverses the aging of mice. What works for rodents, de Grey hopes, will someday work for humans. How will the winner be chosen? All a team has to do is extend a lab mouse's life beyond the current record of 4.98 years - the equivalent of a 150-year-old human.
Every little bit helps - and that goes for donations too. The number of donors matters just as much as the current prize total when it comes to attracting media attention and wealthy sponsors. So step up to the plate and put in a little money - it's a well-placed investment for the future of your health and longevity.
The Longevity Meme Folding@Home team is moving up in the rankings thanks to the new members who joined since my last reminder. All this competition is in a good cause, as outlined at the Folding@Home website:
Proteins are biology's workhorses - its "nanomachines." Before proteins can carry out their biochemical function, they remarkably assemble themselves, or "fold." The process of protein folding, while critical and fundamental to virtually all of biology, remains a mystery. Moreover, perhaps not surprisingly, when proteins do not fold correctly (i.e. "misfold"), there can be serious effects, including many well known diseases, such as Alzheimer's, Mad Cow (BSE), CJD, ALS, Huntington's, and Parkinson's disease.
Folding@Home is a distributed computing project which studies protein folding, misfolding, aggregation, and related diseases. We use novel computational methods and large scale distributed computing, to simulate timescales thousands to millions of times longer than previously achieved. This has allowed us to simulate folding for the first time, and to now direct our approach to examine folding related disease.
Michael Cooper emails to note:
The Longevity Meme is now being tracked at Extreme Overclocking, a large popular group. ... Since TLM moved into the top 800, it is being followed here:
Click on The Longevity Meme entry,
Provides detail, similar to Statsman, about TLM's team.
Send your spare processing cycles to help research into the fundamental biochemistry of age-related conditions ... and boost the rank of the Longevity Meme team. Download the Folding@Home client and join our team today!
From InfoZine, a mainstream view of calorie restriction as a tool for healthy longevity. As is - unfortunately - typical, this article focuses on health benefits rather than longevity, but the results of recent studies are percolating through the medical establishment. "Besides influencing your weight, some studies suggest that avoiding excess calories may directly affect your cancer risk. Laboratory studies show that calorie restriction can lead to fewer and smaller breast cancers. It also appears to inhibit all cancers by slowing down the development of cancer cells, increasing their self-destruction and reducing DNA damage. Furthermore, one study shows that long-term calorie restriction by people with a healthy weight may also lower their blood cholesterol and blood pressure and significantly reduce heart-threatening build-up in blood vessels."
CNN is running a series of articles on visions for the future from noted luminaries and thinkers. From biogerontologist Aubrey de Grey: "It is 2020. Life expectancy is still in the 80s and the world record life span is still 122. But humanity's attitudes to aging are unrecognizable from a decade ago, because of techniques that greatly extend the healthy life span of normal mice -- with therapies only begun at middle age." I can't say as I agree with all of Aubrey de Grey's thoughts on the immediate social changes this will bring - but his Strategies for Engineered Negligible Senescence (SENS) and Mprize projects are worthy of far greater attention and funding than it has recieved to date.
You'll recall that aging researcher Leonid Gavrilov was looking for suggestions on a Perspectives piece for the Science Advisory Board. You can find a recent draft copy via the always useful transhumantech list:
This Perspectives paper was commissioned to me for the Internet community of about 25,000 lab scientists, who are unfamiliar with aging and life-extension research. Hopefully this paper may help to increase public support for scientific studies on aging and life-extension.
If so, then why should we care about caloric restriction at all? Well,the answer to this question is that we can study the mechanisms of anti-aging action of caloric restriction, and this may help us to develop drugs that mimic the positive anti-aging effects of caloric restriction, while being free of its negative side effects. Also in this case there will be no need to impose severe limitations on human diet requiring a strong willpower. In other words, the caloric restriction is not an ultimate solution to the aging problem, but rather a light in the end of a tunnel, which gives us a hope and shows the way to go.
One thing is for sure: The dietary guidelines alone will not allow to defeat aging and to extend healthy lifespan beyond current longevity records. To achieve these goals we need concentration of the best minds and resources (like Manhattan project). These resources are unlikely to come from federal funding overstretched by war efforts, but perhaps they might come from such wealthy visionaries like George Soros, Bill Gates and Pierre Omidyar, who could make a difference.
Much of the currently funded research that pertains to healthy life extension is in the field of calorie restriction, calorie restriction mimetics and other ways to extend life through manipulating metabolic processes. As Gavrilov points out, this is not a path that will lead to radical life extension, but it is a step towards wider acceptance and understanding of the fight to cure aging. In terms of philanthropy, Gavrilov is clearly in much the same camp as biogerontologist Aubrey de Grey - he sees evangelism of healthy life extension to wealthy philanthropists to be a viable way forward in the face of conservatism within the gerontological community.
Medical News Today reports on a first step towards gene therapies for rheumatoid arthritis. A newly identified gene, Foxo3a, "may open a new window for treating arthritic conditions caused by immune dysfunction. Currently, most treatments in development for these disorders focus either on preventing wayward immune cells from attacking the joints or on reducing the ability of these cells to open fire. The new results suggest it may be just as helpful to let these cells kill themselves and each other. ... evolution has somehow provided protective mechanisms for innate immune cells when they go into the hazardous inflammatory environments they create. They need ways to keep themselves alive, and Foxo3a is one of those ways." Remove that ability and errant immune cells cannot survive to do damage.
Here's a little something from PubMed for those who like to keep tabs on telomere research and its application to healthy life extension: "We examined telomere biology in rabbits to expand the comparative biology of telomere-directed replicative senescence within mammals. ... The leporids neither exhibited cellular senescence after sustained periods in culture nor displayed detectable telomerase activity. Continued culture was possible because of their extremely long telomeric arrays. Immunofluorescence showed robust telomere signals at chromosome ends and significant internal chromosomal staining in some instances. ... These results show that it is unlikely that lagomorphs use telomere shortening and replicative senescence as a tumor protective mechanism.
As you might (or might not) have noticed, I'm currently experimenting with text ads for the Mprize for anti-aging research, using Google AdWords and Yahoo! Search Marketing (YSM), formerly Overture. Please refrain from running off to find and click them - I'm assuming that the folks reading Fight Aging! already know about the Mprize and what it aims to achieve. This experimentation aims to introduce the Mprize to folks who haven't heard about it before and gain some experience for later low-cost advertising campaigns. The Mprize is sufficiently different from both the Longevity Meme and Fight Aging! to prevent me from simply copying my existing keyword advertising lists and working from there, however.
I prefer YSM for the initial stages of this sort of experimentation, since it's more a much more time-consuming affair to get Google's automation to play ball for healthy life extension and related topics. The current YSM keyword list looks something like this:
anti aging pill
effects of aging
aging with dignity
anti aging medicine
anti aging product
anti aging therapy
longevity and aging
Of these, the first four are the most successful to date; the number of click-throughs is nothing to write home about, but the click-through rate is high. Meanwhile Google confirms that "aging disease" and "aging research" are good in AdWords, but I haven't been able to convince the system there to keep my keywords active for a number of other prospects.
I'm now soliciting suggestions from the floor as to other, higher traffic keywords I can try. Those and other thoughts on modes of low cost advertising would be greatly appreciated.
From Canada.com, a reminder that osteoporosis - age-related bone loss - is both common and unpleasant: "Osteoporosis is one of the most prevalent diseases of aging, affecting 1.4 million [of 32 million] Canadians. It is characterized by the deterioration of bone density, leading to increased fragility. It is a sneaky disease as bone loss occurs without any symptoms. While it largely afflicts those over 50, it can strike at any age. Twice as many women as men are affected." This is just one of many equally disabling conditions that high levels of funding for healthy life extension research could address. More resources must be directed towards addressing the root causes of age-related degeneration: that is the way to make rapid progress towards longer, healthier lives within our life spans.
The President's Council on Bioethics, a body led by a man who wants to force us all to suffer age-related degeneration and die and intended to put a rubber stamp on restrictive anti-research policies, is up to its normal tricks in the latest publication on "alternatives" to embryonic stem cell research. From one of the few remaining less conservative members: "Michael Gazzaniga, a professor of neurology at Dartmouth College, in a rebuttal to the council report said the proposed alternatives are 'high-risk gambles' and evade the question as to whether the United States should endorse embryonic stem cell research as it currently is done or whether the country will 'remain hostage to the arbitrary views of those with certain beliefs about the nature of life and its origins.'"
MSNBC is running a general interest article on stem cell research with the normal mainstream media emphasis on politics and public debate. "There is nothing controversial in and of itself about research on stem cells, which promise wondrous breakthroughs in treating thousands of diseases because of their potential to grow into many different kinds of tissue. Already, they are being used to create skin grafts, repair stricken hearts and generate bone marrow for patients with lymphoma and leukemia. The disagreements arise when you start talking about where those cells come from." So much effort is currently going into blocking medical advances and slowing down progress towards regenerative cures for age-related diseases.
I think that a recent Wired piece on low cost biotechnology reinforces the points I have made on the future of open source biotechnology development and healthy life extension.
The era of garage biology is upon us. Want to participate? Take a moment to buy yourself a molecular biology lab on eBay. A mere $1,000 will get you a set of precision pipettors for handling liquids and an electrophoresis rig for analyzing DNA. Side trips to sites like BestUse and LabX (two of my favorites) may be required to round out your purchases with graduated cylinders or a PCR thermocycler for amplifying DNA. If you can't afford a particular gizmo, just wait six months - the supply of used laboratory gear only gets better with time. Links to sought-after reagents and protocols can be found at DNAHack. And, of course, Google is no end of help.
Still, don't expect to cure cancer right away, surprise your loved ones with a stylish new feather goatee, or crank out a devilish frankenbug. (Instant bioterrorism is likely beyond your reach, too.) The goodies you buy online require practice to use properly. The necessary skills may be acquired through trial and error, studying online curricula, or taking a lab course at a community college. Although there are cookbook recipes for procedures to purify DNA or insert it into a bacterium, bench biology is not easy; the many molecular manipulations required to play with genes demand real skills.
A wide range of applied biotechnology development is no more complicated than applied electronics - and the present results of the work of an initially small group of garage entrepreneurs in that field are fairly impressive. Good things happen when the price point of participation becomes low enough: there's never any shortage of ideas and skill compared to capital.
As reported by the BBC, mortality rates are the lowest ever - another way of looking at the results of medical advances that increase life expectancy, reduce chronic disease and improve healthy life span. "In 2004, the number of deaths dropped by 5.4% to 7,576 per million for men and 5.5% to 5,279 for women. ... That was the lowest since 1954 ... The ONS has stressed it is part of a long-term decline in mortality rates." We can expect next year and the year after to be even lower as these trends continue. The flip side of the coin is that "lowest" is nowhere near "low enough for my liking" and the trend of increasing life span is not yet fast enough to reach escape velocity to radical life extension. Much more funding needs to go towards directed anti-aging research to achieve those goals.
There is a certain type of person who, when presented with a given scenario, will instantly jump to the boundary conditions and edge cases to try and probe the limits of what he or she is facing. This, I think, is why discussions on immortality - even the colloquial meaning of "vulnerable agelessness" resulting from a way to halt or reverse the aging process - have a way of slipping into discussions of cosmology: the life span and end states of the universe.
Personally, I'd hate to be put in the position of having to make any sort of long term plans based on cosmological certainty today. The field has been in the throes of tremendous change for the last twenty years - brought on by expanding computing power and new observational technologies - with no signs of letting up soon. Today's balance of competing models for the far future of the universe is very different from the consensus five years ago, and it will no doubt look just as different in another five years.
So discussing cosmology in the context of long term plans for transhumanist-style ageless physical immortality - worrying about risk functions, how to reduce accidental death rates to miniscule levels, reengineering the body and mind to support vastly longer life spans - isn't really a serious activity in my mind. Sure, it's fun to talk about it, but it's a form of escapism - just like avoiding the topic of death and the present fight to cure aging. Cosmological research, society and science will undergo amazing, accelerating advances and changes in just the next century ... but none of us will be around to see the end results if we don't ensure that the first steps towards effective healthy life extension and the defeat of age-related degeneration are taken now.
By all means talk about these things, but first things first, folks. We have a lot of work to do before we'll need to worry about cosmological changes interfering in the continuation of our daily lives.
The Mayo Clinic has a fairly sensible, conversative article on the sorts of products currently pushed by the "anti-aging" marketplace - and calorie restriction, which is not. The bottom line is that the science simply is not there to support most claims made by sellers in the marketplace; calorie restriction is the gold standard for scientific backing in present day healthy life extension techniques, and little else rises to that level. That said, the value of supplementation, exercise and calorie restriction in improving health and resisting age-related disease are well backed by research. If you want to be active and alive to benefit from working anti-aging medicine developed in the future then you have to take best care of your health here and now.
Researchers have taken another step towards a complete understanding of the biochemical mechanisms of Alzheimer's disease: "Researchers at the Department of Energy's Lawrence Berkeley National Laboratory have discovered an unsuspected subunit of the protein complex gamma-secretase, which plays a central role in Alzheimer's disease. The researchers have shown that the newly discovered component, the protein CD147, regulates the production of the toxic peptides that cause amyloid plaques, the brain lesions that are the defining feature of Alzheimer's." Understanding at this level, enabled by falling costs in modern biotechnology, is important because it enables scientists to work towards targeted, precise therapies.
EurekAlert reports on yet another new trial for a first generation stem cell therapy for heart damage. "The University of Pittsburgh Medical Center (UPMC) is beginning a clinical trial to evaluate the safety and feasibility of a potential treatment for congestive heart failure that involves injecting a patient's own bone marrow-derived stem cells directly into the heart muscle. The procedure is expected to be performed in five to 10 patients who are scheduled to receive a heart assist device as a bridge to organ transplantation." Other similar studies are also currently underway - there would no doubt be more and greater progress if the overly conservative FDA wasn't holding matters up.
The New Scientist gives a overview of the "green theory" of aging - "that evolution has favoured cells that opt out of the detox business and allow molecular detritus to pile up. Gems and McElwee now believe that ageing is largely due to a breakdown in routine waste disposal and maintenance ... In the end, the crud piles up and poisons your cells. ... And what of the prospects for using the green theory to combat the problem of human ageing? As it is more general than, say, free-radical theories of damage, you'd probably have to do lots of different things to keep the junk at bay. But the hope is that one or two of the genes involved in this system will turn out to have big effects all by themselves. Then, perhaps, we can learn to harness their effects, and live longer lives. "
An article of general interest to transhumanists and healthy life extension advocates is to be found at Reason Online. Ronald Bailey takes on the "democratic socialist" arm of transhumanist thought:
Technologies dealing with the birth, death and the meaning of life need protection from meddling - even democratic meddling - by others who want to control them as a way to force their visions of right and wrong on the rest of us. Your fellow citizens shouldn't get to vote on whom you have sex with, what recreational drugs you ingest, what you read and watch on TV and so forth. Hughes understands that democratic authoritarianism is possible, but discounts the possibility that the majority may well vote to ban the technologies that promise a better world.
However, even as he extols social democracy as the best guarantor of our future biotechnological liberty, Hughes ignores that it is precisely those social democracies he praises, Germany, France, Sweden, and Britain, which now, not in the future, outlaw germinal choice, genetic modification, reproductive and therapeutic cloning, and stem cell research. For example, Germany, Austria and Norway ban the creation of human embryonic stem cell lines. Britain outlaws various types of pre-implantation genetic diagnosis to enable parents to choose among embryos.
Furthermore, Hughes's analysis is largely free of economics - he simply ignores the processes by which wealth is created and gets busy redistributing the wealth through government health care and government subsidized eugenics. After reading Citizen Cyborg, you might come away thinking that Hughes believes that corporations exist primarily to oppress people.
Healthy life extension research - in effect, the right to live - is currently suffering from socialist ideals, just like all other branches of medical research. Socialism itself brings inefficiency, oppression, poverty and lack of freedom, slowing and blocking research that will lead to longer, healthier lives.
A recent News-Medical.net article is interesting in light of research into age-related stem cell decline and rejuvenation. "Declining function of cells that help repair the inner lining of blood vessels, known as endothelial progenitor cells, rather than a dwindling supply of the cells, may underlie the increased risk of atherosclerosis and other vascular diseases as people grow older ... The report [suggests] that it is not the quantity aspect of these cells produced by the marrow that fails with age, but instead, the quality of the precursors that become limiting, thus leading to deficient repair." This ties in very nicely with what is seen elsewhere in the body; this work suggests that more research should be directed to understanding whether chemical cues can restore the function of these cells.
Something good via Genetic Engineering News: human embryonic stem cells (hESCs) "can be differentiated into [hematopoietic stem cells (HSCs)], the cells which produce all of the cellular components of blood. When transplanted into immune deficient mice, the hESC-derived HSCs survive and establish multi-lineage hematopoiesis-producing human lymphocytes, red blood cells, and myeloid cells." In other words, "this work provides strong evidence that functional [blood] stem cells can be derived from human embryonic stem cells." Control over cellular differentiation is key to much of the future of regenerative cures for age-related disease. It is very gratifying to watch this important work progress, step by step.
As a recent ScienceDaily release points out - if we ignore the cries for more public funding in the guise of general doom and gloom regarding the current state of medicine - vaccination has had an enormous effect on health and prevalence of chronic disease in the time since its development:
A comprehensive system of vaccine development in the U.S. resulted in a reduction of 87 to more than 99 percent in illness from ten vaccine-preventable diseases during the twentieth century.
In addition to the major reductions in illness during the twentieth century from smallpox, diphtheria, measles, mumps, pertussis, polio, rubella, congenital rubella syndrome, tetanus, and H. influenzae, type b (in children less than 5 years old), new vaccines in the past 10 years for varicella (chickenpox), hepatitis A, and pneumococcal disease have led to significant reductions in disease in young children, including a drop of 92 percent in mortality from chickenpox in children four years and younger.
Quite aside from mortality rates and their effect on life expectancy, less chronic disease means less cellular and other forms of biochemical damage accumulated over a lifetime - and thus, by the Reliability Theory of aging, a better chance at a longer, healthier life. This class of explanation for historical gains in life span is explored elsewhere at Fight Aging!, so feel free to take a look. You might find some related musings on the fight against infectious disease interesting as well.
The BBC reports on the longer term results of 2002 trial for an Alzheimer's vaccine, a way of inducing the body to attack beta amyloid: "Results from the long-term follow up studies show 59 out of 300 patients who received at least one dose of the vaccine produced a significant immune response. This group performed significantly better on a series of memory tests than those who received a dummy injection. Brain scans also showed that their brains shrank in size - possibly because of a removal of built-up beta amyloid deposits." More sophisticated vaccine trials are already underway - this seems to be a promising approach to date, all told.
The transcript for the latest SAGE Crossroads webcast is available. To quote the Foresight Institute's Christine Peterson, "we want a system that works at the molecular level, that gives you the benefits of surgery, three-dimensional control, bring it all the way down to the molecular level, and combine it with the chemical action of drugs, to change bonds, do the kinds of things you need to do to actually heal the patient. ... You can read about this in a series of books, for example, which start with the word 'nanomedicine.' If you were interested in the future of medicine, in the long-term future, the books on nanomedicine would be a place to start." She goes on to a good discussion of healthy life extension research and those who oppose it - well worth your time to read.
I've often made parallels with the alchemists and their three goals of transmuting the elements, achieving flight, and immortality. I like to say: two down, one to go.
The alchemists were pre-scientific, of course, but had their heart in the right place.
Has to be said, I wish we were further along with the last goal there - but whatever you might think of that remark, it's food for thought.
Bruce J. Klein of the Immortality Institute dropped by today to shoot some interview footage for "Exploring Life Extension". Bruce has been traveling the length and breadth of the US for months now, meeting members of the healthy life extension community and racking up more than a hundred hours of tape. It's an open question as to whether anything I said is compelling or useful enough to make it into the final version or subsequent use of footage, but we shall see.
The film is a good and worthwhile project, but more interesting to me is the web of contacts and relationships that Bruce is putting together in his capacity as Immortality Institute chair. Journalists, scientists, businessmen, community leaders, and so forth, many of whom are names you'll recognize. As a fairly immediate extension of the rumor circuit and grape vine, Bruce indicated that there's a lot more going on out there in the community than makes it to a level at which I'm going to notice. Which leads me to conclude, once again, that healthy life extension advocates are being nowhere near vocal enough about their efforts. If I don't know about it, you can be sure that most of the rest of the world doesn't know about it either ... and as I tend to restate every now and again, that's a big part of our funding and credibility problem.
I mean, come on folks. We all know that the science of healthy life extension is "just" details, money and work. The high level path for technology and development to greatly extend the healthy human life span is clear. The big problem is one of public awareness, education and support. Not enough people know what is possible - so if you're off out there doing your part to get things done, make more noise about it! We've moved beyond the stage at which minor efforts at publicity vanish into the wild; there are enough people online and offline, professional and amateur, who write on this topic to act as an effective echo chamber and amplifer now. Give them something to write about.
But onwards: the logical next step would be to monetize Bruce's large and expanding network of relationships in order to fund a high profile healthy life extension project under the Immortality Institute banner. What could this be: a research prize, a major media project with mainstream distribution, or something different and more out of the box? There are many options, many doors opened by means of contacts made and proof of capability. We shall see how it turns out.
The San Francisco Examiner reports on lawsuits launched in opposition to embryonic stem cell research and the California Institute for Regenerative Medicine (CIRM). "Though the objections are related to fiscal oversight, the groups are represented by the Life Legal Defense Fund, which morally objects to embryonic stem cell research because days-old human embryos must be destroyed to collect the cells. State officials have insisted that the two suits have no merit but admit that they cannot borrow any funding while they are pending. ... if there is no way to approve bonds with the suits pending, the state [should] consider asking nonprofits to advance as much as $100 million." A "days-old human embryo" being an undifferentiated spherical clump of a hundred cells, of course, essentially the same as skin flakes shed every day.
The next symposium organized by the Buck Institute for Aging Research in October 2005 will "bring together investigators from diverse backgrounds to address the current status of the pharmacology of aging and tackle the challenges associated with the discovery of compounds that slow aging. As genetic interventions have resulted in spectacular progress in our understanding of the aging process, now pharmacological interventions promise to advance it further. The Buck Institute Symposium will focus on targets for interventions in aging, developing screens for anti-aging compounds, applied drug discovery and the criteria for successful pharmacological interventions." I suspect this will largely focus on manipulation of metabolism, given the work that makes up the bulk of funded anti-aging research today.
It's been a slow weekend for both news and my brain, more is the pity, so I'm reduced to pointing out research that suggests a modicum of "good stress" is good for longevity:
Dr Kyriazis, the medical director of the British Longevity Society, argued that moderate stress increased the production of proteins that help to repair the body's cells, including brain cells, enabling them to work at peak capacity.
"Research shows that cells subjected to stress repair themselves, allowing us to live longer," he said.
"As the body ages, this self-repair mechanism starts to slow down.
"The best way to keep the process working efficiently is to 'exercise it', in the same way that you would exercise your muscles to keep them strong."
"Good stress" in this context results from activities that require effort, learning and time management, but are not simply execises in frustration or feeling trapped. This is akin to normal exercise, supplementation or calorie restriction in terms of managing your health using present day knowledge and lifestyle choices - we know that it's a good thing to do, it will lengthen our lives and delay age-related disease ... but we can't use it to obtain what I would regard as significant healthy life extension. Yet far too much attention and time is put towards these issues rather than into, say, raising the profile of directed longevity research. Science is capable of providing us with far better than the absolute best we could ever manage with present day techniques for maintaining our health and lengthening our healthy life spans. Think regenerative medicine, stem cells, nanomedicine, therapies to repair mitochondrial free radical damage, the whole engineered negligible senescence plan. We should put more effort into supporting the advance of science into the realm of radical health life extension and less into tinkering around with present day methodologies that have a much more limited potential payoff.
Since its launch in 2003, the Mprize - or Methuselah Mouse Prize for anti-aging research - has gathered $1.25 million in pledges and donations from the healthy life extension community. The Mprize is on the way to breaking the research funding logjam in the gerontological community - encouraging more researchers to develop therapies that extend healthy life span and thus open the funding floodgates for directed, scientific anti-aging research. Your support is needed to make this happen! Donate today to place your vote, to have your say, for better medicine and longer lives. Make your opinion count and join The Three Hundred: show that you care about the future of health and longevity and you want to see something done.
As many sources have noted, the California Institute for Regenerative Medicine (CIRM) has settled on San Francisco to host its new headquarters. The San Francisco Examiner gives slight insight into the sort of bidding war with public funds and private donations that went on behind the scenes; it looks like we can expect international stem cell research conferences and other addendums to the business of CIRM in the future. Given the timing of events to date - even fast as they have been for government work - those folks who speculated that grants would not be awarded until 2006 may yet be proven right. "Now that the real estate competition is over, we must focus our collective energy on supporting the critical work of stem cell research; finding cures for diseases and saving lives."
Cambridge Massachusetts 2003 venture capitali start-up Helicos Biosciences claims that by 2007 Helicos will be selling a machine that will sequence a person's genome for $5000.
Incredibly cheap DNA sequencing will be occasion for a massive biomedical and social science project to compare the DNA sequences and large amounts of biomedical and behavioral and other information between millions of people.
Some of the commenters have expressed skepticism as to the plausibility of this timeline (rightly so, I suspect - it seems a little aggressive). However, the more important thing here is that venture funding organizations have bought into this timeline ... and are presumably still buying into this timeline. This is the sort of short time frame that venture investors like to put money on; hence more funding leading to more progress across the board leading to more aggressive estimates of short time frames. It's a positive feedback loop that drops ever more money into development until breakthroughs are made or the bottom drops out of this miniature bubble.
Finding a gene commonly associated with age-related conditions or damaging processes - like the inflammatory response - is a very good thing. With a gene in hand, researchers can make good progress towards an understanding of the biochemical processes involved, and thus craft a direct, targeted therapy. ScienceDaily has this to say: "The gene variant was first identified in an animal model ... The researchers discovered that people with the variant ran a 20-40 per cent greater risk of developing rheumatism, MS or a myocardial infarction. The gene variant is also common: an estimated 20-25 per cent of the population carry it. ... This gene variant can therefore be one of the single largest genetic causes of complex diseases with inflammatory components."
The BBC provides an overview of recent research into why stem cells fail with age and what can be done about it: "The study found special stem cells come to the rescue of damaged young muscles, but are not triggered in older ones. ... tests on mice suggest something in young blood spurs the stem cells into action to repair the muscle damage. ... We need to consider the possibility that the niche in which stem cells sit is as important in terms of stem cell aging as the cells themselves. ... This is an exciting leap in the research. It proves the fact that you can reverse this problem. But it's no small task to identify the factor in the blood that's involved." It's good to see this work gaining wider notice.
I'm preaching to the choir, I realize, but calorie restriction is a very good thing to look into if you haven't already. This MSNBC article takes the kinder, gentler approach: "Laboratory studies show that calorie restriction can lead to fewer and smaller breast cancers. It also appears to inhibit all cancers by slowing down the development of cancer cells, increasing their self-destruction and reducing DNA damage. ... Furthermore, one study shows that long-term calorie restriction by people with a healthy weight may also lower their blood cholesterol and blood pressure and significantly reduce heart-threatening build-up in blood vessels." You have to take best possible care of your health and longevity today if you want to live to see working anti-aging medicine in the future.
Stem cell research is becoming a healthy (and healthily funded) field of science despite political opposition to developing cures for age-related conditions - you can tell by the rate at which new institutes are endowed. EurekAlert notes that "Financier Leon D. Black has committed $10 million to Mount Sinai School of Medicine to establish the Black Family Stem Cell Institute. The Institute, which will be directed by Gordon Keller, PhD, Professor of Gene and Cell Medicine, will integrate research in embryonic stem cells, developmental biology, and adult stem cell biology." This sort of philanthropic endowment is the visible tip of the funding iceberg, and something we would like to see in the near future for serious anti-aging research.
Chances are you'll still be in no hurry to die if 100 years from now life is still rewarding. You may still feel the same in 1000 years. This is also an answer to those who might not want life extension. De Grey is not arguing for mandatory immortality. He's arguing against mandatory age-related death.
It's not life that gets old. It's the getting old that gets old.
People are funny creatures; too many of them think that they'll get bored with a life that is a few decades longer than the current standard. But I know from experience that I can get bored in a matter of a few minutes, an hour tops, if I really put my mind to it - as could anyone else. So if you can accept the possibility of an interesting and rewarding life of 80 years, why not one of 150? Or 1000?
Betterhumans reports on modest healthy life extension in mice, achieved by boosting their protection from damaging free radicals. "Rabinovitch and colleagues focused on the enzyme catalase, which helps convert hydrogen peroxide into water and oxygen. This is important because hydrogen peroxide is a waste product of metabolism that can be a precursor of free radicals. The researchers studied mice with a genetic variation that made them produce extra human catalase. ... Mice with higher catalase levels in the mitochondria had about a 20% increase in average and maximum lifespan." Scientists have already shown that life extension at this level is quite plausible through manipulation of metabolic processes.
Early stage work in the manipulation of cellular and bacterial mechanisms is covered by the Telegraph: "Proponents aim to make living cells function as if they were tiny computers so they can be harnessed as workhorses that detect toxins by glowing, help to build things, or repair tissues and organs within the body. ... They want, for example to design a cell that will swim around blood vessels and digest fatty deposits on artery walls." Researchers are not too far beyond the stage of creating basic patterns and cellular devices as a proof of concept - but computer scientists were at that same early point not so many decades ago. The future looks interesting indeed.
It has to be said, I feel odd pointing to a Michael Fumento piece as something worth reading. That, given his anti-science positions on embryonic stem research and blatant cherry picking of studies to support them. The man seems to be on more solid ground with the topic of weight, mortality, health and longevity - and that recent study that too many people have taken entirely the wrong way - however.
These all dovetail with findings that in every species from worms to monkeys, calorie restriction increases longevity. The leanest animals also look and act younger. In the only calorie restriction analysis of people, "The results clearly suggest that humans react to such a nutritional regimen similarly to other vertebrates." If Flegal's findings were valid, they would stand biology on its head.
As Wired notes, "a small piece of a planarian worm can regenerate an entire new body. The worm's ability to regenerate is so powerful that a tissue fragment only 1/279 of the worm's length can grow into a new animal." Researchers have been working to identify all the genes involved in this regenerative process - if human medicine can benefit from understanding salamander regeneration, then it will likely benefit from research into lower forms of life as well. "It's too soon to tell whether research into planarian worms might one day let doctors regrow amputated limbs or diseased organs in people. Nevertheless, since many of the genes found in flatworms are also present in humans, scientists believe they may provide insights into how to use adult stem cells to replace diseased or damaged human tissue."
Randall Parker of FuturePundit adds his thoughts on the future of unique personalized medicine heralded by falling costs. "Precise disease prediction will be feasible for many diseases. For example, I would expect disease prediction to be much more feasible for osteoarthritis, heart disease, kidney disease, and other ailments that strike once sufficient damage has accumulated over time. Also, predictive capabilities will become more useful as our toolbox of treatments expands. Why wait for a knee to become painful and severely damaged if we can detect the problem years earlier and send in stem cells to do repairs before repair becomes much more difficult."
People tend to be frightened by new ideas, but we need to recall that average life expectancy a century ago was only 47 years, but has now increased to 77 years today. This is a 63 per cent increase. The rate of technological progress is accelerating, and it is highly likely that we will see the same type of increase in life expectancy that occurred in the last century (1900-2000) to occur in the first 20 years of the present century (2000-2020). A 63 per cent increase in life expectancy would mean life spans of over 125 years in the next few years. As the biotechnology revolution begins to unfold (what we refer to as Bridge Two in our book), radical increases in life expectancy will result from several intersecting technologies that are already making their way from the research laboratory to patient care: stem cell therapies (using not only politically sensitive embryonic stem cells, but umbilical cord blood stem cells and even adult stem cells), therapeutic cloning (creation of specific cell types and organs as replacements for defective tissues and organs), bioengineered drugs and gene-based therapies (blocking the expression of harmful genes or their replacement with healthful genes). This will lead to Bridge Three, which will involve the full flowering of the nanotechnology and artificial intelligence revolutions, now in their infancy.
From ScienceDaily, an article on an elegant class of potential cancer therapies. This is a good example of what can be achieved with a greater understanding of biochemistry: existing mechanisms hooked together to produce a controlled biological system that attacks only cancer cells and can be turned on and off as needed. "[An antibody currently in clinical use], with the attached alliinase in tow, soon found and bound to the target cancer cells. Subsequently, the mice were repeatedly injected with the inert chemical alliin which, upon contact with alliinase, was processed into allicin molecules directly on the cancer cell's surface. Within three days, almost all of the human lymphoma cancer cells were destroyed in those mice."
An alternate path towards regenerative medicine - that requires a deeper understanding of cellular mechanisms - involves manipulating genetic and biochemical cues to induce cells into regeneration. EurekAlert reports that "heart-muscle cells, or cardiomyocytes, were previously considered incapable of replicating in mammals after birth, which is why heart attack is such a problem: once killed, heart tissue can't regenerate. Dr. Mark Keating and Dr. Felix Engel now show that an enzyme known as p38 MAP kinase suppresses cardiomyocyte replication, and that inhibiting p38 enables these cells to proliferate. ... This is just one baby step toward regenerative therapy, but it's an important one. Inhibiting p38 is now a candidate therapeutic strategy."
Who says that libertarians can't write articles that are simultaneously good and entertaining? Here's one from Bill Walker that covers a wide range of topics, from the evil done by centralized state control over medicine to cancer, telomeres and future therapies:
If telomerase inhibitors were a new kind of computer chip, they would have been on every Wal-Mart pharmacy shelf and selling for ten dollars a bottle by now. ... In a free system, life insurance companies, consumer magazines, and other competing interests would provide medical databases. Maybe even the AMA would become a force for "truth-in-medicine," as it was to some degree before the creation of the FDA. Under common law but free of arbitrary regulation, drug development would be as fast as computer development. Cancer would be extinct and human beings would finally, really, own their own bodies.
The Mprize for anti-aging research gets a link in the piece as well - something I'd like to see more of.
The Betterhumans magazine - the online face of transhumanism these days, so far as eyeballs and page views go in any case - is giving a sneak preview of their shiny new site design. It looks good and not-so-coincidentally happens to feature a nice new Mprize total display and prominent placement of biogerontologist Aubrey de Grey. Good job, I think - but take a look and see for yourself.
Why do stem cells - and thus our ability to heal - falter in effectiveness as we age? This Newswise release outlines the results that suggest "this behavior may be regulated by genetic mechanisms found in most human cells ... The current thinking is that there must be some unique 'stemness' gene that no other cell expresses, but what we found is that what makes stem cells special -- their ability to renew themselves and differentiate into other tissue types -- may be attributed to fundamental mechanisms of cell physiology common to all cells. ... The difference between those robust, self-replicating young [stem cells] and older cells appears to be the degree of expression of these two regulatory genes governing fundamental cell physiology." Might it be possible to restore old stem cells to youthful vigor?
EurekAlert reports on new understanding of age-related macular degeneration: "Age-related macular degeneration, the leading cause of blindness in the elderly, occurs when a common inherited gene variation is triggered, possibly by an infection, according to a new study ... The gene, known as Factor H, encodes a protein that regulates immune defense against infection caused by bacteria and viruses. People who have an inherited variation in this gene are less able to control inflammation caused by these infections, which may spark age-related macular degeneration (AMD) later in life, the study finds. ... By targeting the molecules involved in inflammation and its regulation we believe we can begin to develop therapies and diagnostic tools that could help countless people keep their sight."
Today I am starting to write a new Perspectives paper, and I am asking for your help and advice. ... I am invited to write a Perspective paper on caloric restriction, which in my mind has been transformed to a broader topic with a title:
"Life Extension, Caloric Restriction, and Scientific Philanthropy"
This Perspective paper is addressed to the audience of about 25,000 biomedical researchers world-wide (members of the Science Advisory Board), and it will be publicly available on the Internet for everybody.
This kind of Perspectives papers may be potentially important for making the Society and potential philanthropists more friendly to ideas of extension of healthy lifespan, so your help and editorial advice on this paper would be greatly appreciated.
He gives some references and enough of a beginning to show the direction he intends to take, so drop by and offer suggestions and references for similar past work.
Medical News Today reports on the first seed grants awarded by the Harvard Stem Cell Institute (HSCI). "The grants will support research aimed at advancing the understanding of stem cell biology and developing new therapeutic approaches to several diseases, among them cancer, diabetes, kidney disease, muscle disease, Parkinson's disease, and retinal blindness. Five of the twelve projects will involve human embryonic stem cells, including using or creating new stem cell lines that are not eligible for federal funding. ... The awards put particular emphasis on projects that might be difficult to fund from other sources either because a project is considered to be 'high risk/high payoff,' or because the research is ineligible for federal funding under the current federal restrictions on human embryonic stem cell research."
A comment in this Sunday Herald article accurately describes what needs to happen in order for the currently small cryonics industry to grow and mature: "Cryonics, ultimately, if proven to work, is going to become an adjunct to emergency medicine. If someone can't be treated, they will be preserved until such time when they can be treated. And it's not going to be the decades-long experiment that it is now; it could be just for a day, a week, a month or a year." Forming those ties to mainstream emergency medical practices via spin-off technologies and research is the way to a healthier, larger cryonics industry. If a realistic present day alternative to dying is to be available to more than a handful of people, this has to happen.