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Fundraiser by Lifespan.io & CellAge: Targeting Senescent Cells With Synthetic Biology

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Categories: Announcements, Science, Transhumanism, Tags: , , , , , , , , , , , , ,

The New Renaissance HatCellAge
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Editor’s Note: The Rational Argumentator and the U.S. Transhumanist Party support Lifespan.io and CellAge in their work towards groundbreaking scientific life-extension research. Finding a way to repair age-related damage to senescent cells would be a fundamental breakthrough for transhumanism, and we offer our best wishes and support for those striving towards these new technologies.

               ~ Gennady Stolyarov II, Editor-in-Chief, The Rational Argumentator, December 11, 2016

From Lifespan.io and CellAge:

Our society has never aged more rapidly – one of the most visible symptoms of the changing demographics is the exponential increase in the incidence of age-related diseases, including cancer, cardiovascular diseases and osteoarthritis. Not only does aging have a negative effect on the quality of life among the elderly but it also causes a significant financial strain on both private and public sectors. As the proportion of older people is increasing so is health care spending. According to a WHO analysis, the annual number of new cancer cases is projected to rise to 17 million by 2020, and reach 27 million by 2030. Similar trends are clearly visible in other age-related diseases such as cardiovascular disease. Few effective treatments addressing these challenges are currently available and most of them focus on a single disease rather than adopting a more holistic approach to aging.

Recently a new approach which has the potential of significantly alleviating these problems has been validated by a number of in vivo and in vitro studies. It has been demonstrated that senescent cells (cells which have ceased to replicate due to stress or replicative capacity exhaustion) are linked to many age-related diseases. Furthermore, removing senescent cells from mice has been recently shown to drastically increase mouse healthspan (a period of life free of serious diseases).

Here at CellAge we are working hard to help translate these findings into humans!

CellAge, together with a leading synthetic biology partner, Synpromics, are poised to develop a technology allowing for the identification and removal of harmful senescent cells. Our breakthrough technology will benefit both the scientific community and the general public.

In short, CellAge is going to develop synthetic promoters which are specific to senescent cells, as promoters that are currently being used to track senescent cells are simply not good enough to be used in therapies. The most prominently used p16 gene promoter has a number of limitations, for example. First, it is involved in cell cycle regulation, which poses a danger in targeting cells which are not diving but not senescent either, such as quiescent stem cells. Second, organism-wide administration of gene therapy might at present be too dangerous. This means senescent cells only in specific organs might need to be targeted and p16 promoter does not provide this level of specificity. Third, the p16 promoter is not active in all senescent cells. Thus, after therapies utilizing this promoter, a proportion of senescent cells would still remain. Moreover, the p16 promoter is relatively large (2.1kb), making it difficult to incorporate in present gene therapy vehicles. Lastly, to achieve the intended therapeutic effect the strength of p16 promoter to drive therapeutic effect might not be high enough.

CellAge will be constructing a synthetic promoter which has a potential to overcome all of the mentioned limitations. A number of gene therapy companies, including uniQure, AGTC and Avalanche Biotech have successfully targeted other types of cells using this technology. With your help, we will be able to use same technology to develop tools and therapies for accurate senescent cell targeting.

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Major Mouse Testing Program Crowdfunding Campaign Announcement by International Longevity Alliance

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Categories: Announcements, Science, Transhumanism, Tags: , , , , , , , , , , , , , , , ,

The New Renaissance HatInternational Longevity Alliance

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Editor’s Note: The Rational Argumentator strongly supports the Major Mouse Testing Project crowdfunding campaign, and I have personally pledged $100 to this effort. Furthermore, I am honored that copies of my illustrated children’s book Death is Wrong are being made available as rewards for certain tiers of contributors to this research fundraiser.

~ Gennady Stolyarov II, Editor-in-Chief, The Rational Argumentator, May 11, 2016

The International Longevity Alliance is conducting a crowdfunding campaign to support the investigation of senolytic drugs’ potential to extend life. The team is going to study the combination of three senolytic drugs – Dasatinib, Venetoclax, and Quercetin – in mice, to see if the removal of senescent cells can ensure extended maximum lifespan. With highly devoted scientists and volunteers working for MMTP, the project needs only $60,000 to begin this experiment, as the researchers would need only to buy the mice and pay for their housing, the substances to test, and the battery of tests to analyze health changes.

Will you help to fund this research? Then please go to Lifespan.io, and choose the donation that suits you best and receive the deepest gratitude of the team and a nice useful souvenir to remember your input into the investigation of longevity therapies!

MMTP_Project1_StairFind out more about the International Longevity Alliance here.

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The Two Faces of Aging: Cancer and Cellular Senescence – Article by Adam Alonzi

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The New Renaissance Hat
Adam Alonzi
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This article is republished with the author’s permission. It was originally posted on Radical Science News.

hELA-400x300Multiphoton fluorescence image of HeLa cells.

Aging, inflammation, cancer, and cellular senescence are all intimately interconnected. Deciphering the nature of each thread is a tremendous task, but must be done if preventative and geriatric medicine ever hope to advance. A one-dimensional analysis simply will not suffice. Without a strong understanding of the genetic, epigenetic, intercellular, and intracellular factors at work, only an incomplete picture can be formed. However, even with an incomplete picture, useful therapeutics can be and are being developed. One face is cancer, in reality a number of diseases characterized by uncontrolled cell division. The other is degradation, which causes a slue of degenerative disorders stemming from deterioration in regenerative capacity.

Now there is a new focus on making geroprotectors, which are a diverse and growing family of compounds that assist in preventing and reversing the unwanted side effects of aging. Senolytics, a subset of this broad group, accomplish this feat by encouraging the removal of decrepit cells. A few examples include dasatinib, quercetin, and ABT263. Although more research must be done, there are a precious handful of studies accessible to anyone with the inclination to scroll to the works cited section of this article. Those within the life-extension community and a few enlightened souls outside of it already know this, but it bears repeating: in the developed world all major diseases are the direct result of the aging process. Accepting this rather simple premise, and you really ought to, should stoke your enthusiasm for the first generation of anti-aging elixirs and treatments. Before diving into the details of these promising new pharmaceuticals, nanotechnology, and gene therapies we must ask what is cellular senescence? What causes it? What purpose does it serve?

Depending on the context in which it is operating, a single gene can have positive or negative effects on an organism’s phenotype. Often the gene is exerting both desirable and undesirable influences at the same time. This is called antagonistic pleiotropy. For example, high levels of testosterone can confer several reproductive advantages in youth, but in elderly men can increase their likelihood of developing prostate cancer. Cellular senescence is a protective measure; it is a response to damage that could potentially turn a healthy cell into a malignant one. Understandably, this becomes considerably more complex when one is examining multiple genes and multiple pathways. Identifying all of the players involved is difficult enough. Conboy’s famous parabiosis experiment, where a young mouse’s system revived an old ones, shows that alterations in the microenviornment, in this case identified and unidentified factors in the blood of young mice, can be very beneficial to their elders. Conversely, there is a solid body of evidence that shows senescent cells can have a bad influence on their neighbors. How can something similar be achieved in humans without having to surgically attach a senior citizen to a college freshman?

By halting its own division, a senescent cell removes itself as an immediate tumorigenic threat. Yet the accumulation of nondividing cells is implicated in a host of pathologies, including, somewhat paradoxically, cancer, which, as any life actuary’s mortality table will show, is yet another bedfellow of the second half of life. The single greatest risk factor for developing cancer is age. The Hayflick Limit is well known to most people who have ever excitedly watched the drama of a freshly inoculated petri dish. After exhausting their telomeres, cells stop dividing. Hayflick et al. astutely noted that “the [cessation of cell growth] in culture may be related to senescence in vivo.” Although cellular senescnece is considered irreversible, a select few cells can resume normal growth after the inactivation of the p53 tumor suppressor. The removal of p16, a related gene, resulted in the elimination of the progeroid phenotype in mice. There are several important p’s at play here, but two are enough for now.

Our bodies are bombarded by insults to their resilient but woefully vincible microscopic machinery. Oxidative stress, DNA damage, telomeric dysfunction, carcinogens, assorted mutations from assorted causes, necessary or unnecessary immunological responses to internal or external factors, all take their toll. In response cells may repair themselves, they may activate an apoptotic pathway to kill themselves, or just stop proliferating. After suffering these slings and arrows, p53 is activated. Not surprisingly, mice carrying a hyperactive form of p53 display high levels of cellular senescence. To quote Campisi, abnormalities in p53 and p15 are found in “most, if not all, cancers.” Knocking p53 out altogether produced mice unusually free of tumors, but those mice find themselves prematurely past their prime. There is a clear trade-off here.

In a later experiment Garcia-Cao modified p53 to only express itself when activated. The mice exhibited normal longevity as well as an“unusual resistance to cancer.” Though it may seem so, these two cellular states are most certainly not opposing fates. As it is with oxidative stress and nutrient sensing, two other components of senescence or lack thereof, the goal is not to increase or decrease one side disproportionately, but to find the correct balance between many competing entities to maintain healthy homeostasis. As mentioned earlier, telomeres play an important role in geroconversion, the transformation of quiescent cells into senescent ones. Meta-analyses have shown a strong relationship between short telomeres and mortality risk, especially in younger people. Although cancer cells activate telomerase to overcome the Hayflick Limit, it is not entirely certain if the activation of telomerase is oncogenic.

majormouse

SASP (senescence-associated secretory phenotype) is associated with chronic inflammation, which itself is implicated in a growing list of common infirmities. Many SASP factors are known to stimulate phenotypes similar to those displayed by aggressive cancer cells. The simultaneous injection of senescent fibroblasts with premalignant epithelial cells into mice results in malignancy. On the other hand, senescent human melanocytes secrete a protein that induces replicative arrest in a fair percentage of melanoma cells. In all experiments tissue types must be taken into account, of course. Some of the hallmarks of inflammation are elevated levels of IL-6, IL-8, and TNF-α. Inflammatory oxidative damage is carcinogenic and an inflammatory microenvironment is a good breeding ground for malignancies.

Caloric restriction extends lifespan in part by inhibiting TOR/mTOR (target of rapamycin/mechanistic target of rapamycin, also called  the mammalian target of rapamycin). TOR is a sort of metabolic manager, it receives inputs regarding the availability of nutrients and stress levels and then acts accordingly. Metformin is also a TOR inhibitor, which is why it is being investigated as a cancer shield and a longevity aid. Rapamycin has extended average lifespans in all species tested thus far and reduces geroconversion. It also restores the self-renewal and differentiation capacities of haemopoietic stem cells. For these reasons the Major Mouse Testing Program is using rapamycin as its positive control. mTOR and p53 dance (or battle) with each other beautifully in what Hasty calls the “Clash of the Gods.” While p53 inhibits mTOR1 activity, mTOR1 increases p53 activity. Since neither metformin nor rapamycin are without their share of unwanted side effects, more senolytics must be explored in greater detail.

Starting with a simple premise, namely that senescent cells rely on anti-apoptotic and pro-survival defenses more than their actively replicating counterparts, Campisi and her colleagues created a series of experiments to find the “Achilles’ Heel” of senescent cells. After comparing the two different cell states, they designed senolytic siRNAs. 39 transcripts were selected for knockdown by siRNA transfection, and 17 affected the viability of their target more than healthy cells. Dasatinib, a cancer drug, and quercitin, a common flavonoid found in common foods, have senolytic properties. The former has a proven proclivity for fat-cell progenitors, and the latter is more effective against endothelial cells. Delivered together, they they remove senescent mouse embryonic fibroblasts. Administration into elderly mice resulted in favorable changes in SA-BetaGAL (a molecule closely associated with SASP) and reduced p16 RNA. Single doses of D+Q together resulted in significant improvements in progeroid mice.

If you are not titillated yet, please embark on your own journey through the gallery of encroaching options for those who would prefer not to become chronically ill, suffer immensely, and, of course, die miserably in a hospital bed soaked with several types of their own excretions―presumably, hopefully, those who claim to be unafraid of death have never seen this image or naively assume they will never be the star of such a dismal and lamentably “normal” final act. There is nothing vain about wanting to avoid all the complications that come with time. This research is quickly becoming an economic and humanitarian necessity. The trailblazers who move this research forward will not only find wealth at the end of their path, but the undying gratitude of all life on earth.

Adam Alonzi is a writer, biotechnologist, documentary maker, futurist, inventor, programmer, and author of the novels “A Plank in Reason” and “Praying for Death: Mocking the Apocalypse”. He is an analyst for the Millennium Project, the Head Media Director for BioViva Sciences, and Editor-in-Chief of Radical Science News. Listen to his podcasts here. Read his blog here.

References

Blagosklonny, M. V. (2013). Rapamycin extends life-and health span because it slows aging. Aging (Albany NY), 5(8), 592.

Campisi, Judith, and Fabrizio d’Adda di Fagagna. “Cellular senescence: when bad things happen to good cells.” Nature reviews Molecular cell biology 8.9 (2007): 729-740.

Campisi, Judith. “Aging, cellular senescence, and cancer.” Annual review of physiology 75 (2013): 685.

Hasty, Paul, et al. “mTORC1 and p53: clash of the gods?.” Cell Cycle 12.1 (2013): 20-25.

Kirkland, James L. “Translating advances from the basic biology of aging into clinical application.” Experimental gerontology 48.1 (2013): 1-5.

Lamming, Dudley W., et al. “Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity.” Science 335.6076 (2012): 1638-1643.

LaPak, Kyle M., and Christin E. Burd. “The molecular balancing act of p16INK4a in cancer and aging.” Molecular Cancer Research 12.2 (2014): 167-183.

Malavolta, Marco, et al. “Pleiotropic effects of tocotrienols and quercetin on cellular senescence: introducing the perspective of senolytic effects of phytochemicals.” Current drug targets (2015).

Rodier, Francis, Judith Campisi, and Dipa Bhaumik. “Two faces of p53: aging and tumor suppression.” Nucleic acids research 35.22 (2007): 7475-7484.

Rodier, Francis, and Judith Campisi. “Four faces of cellular senescence.” The Journal of cell biology 192.4 (2011): 547-556.

Salama, Rafik, et al. “Cellular senescence and its effector programs.” Genes & development 28.2 (2014): 99-114.

Tchkonia, Tamara, et al. “Cellular senescence and the senescent secretory phenotype: therapeutic opportunities.” The Journal of clinical investigation 123.123 (3) (2013): 966-972.

Zhu, Yi, et al. “The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs.” Aging cell (2015).

 

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Extending Life in Mice With Artificially Shortened Life Spans is Rarely Directly Relevant or Useful – Article by Reason

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The New Renaissance Hat
Reason
May 4, 2014
Recommend this page.
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There are numerous examples of studies that use mice genetically engineered to suffer forms of shortened life span with the appearance of accelerated aging. One has to be very cautious in reading anything into this sort of work, however: it is rarely of any great relevance to normal aging, as it creates and then attempts to ameliorate an entirely artificial situation. The appearance of accelerated aging is not in fact accelerated aging, but is rather often caused by mechanisms that are of little importance in normal aging. Even when the mechanisms are relevant, the overall metabolic circumstances can render it impossible to determine whether or not a partial treatment will be of any use in normal aging. The gold standard for relevance when evaluating new methods is the extension of life in unmodified mice, but unfortunately this is expensive and slow.

The publicity materials quoted below are a good example of research in animals exhibiting shortened life spans. Here scientists are investigating a protein involved in the induction of cellular senescence. As is often the case, however, from the structure of the work it is impossible to tell whether or not their drug candidate will be of any use as a treatment to lower levels of cellular senescence in normal aging and thus produce benefits such as extended health and life span. Those tests will still have occur:

Quote:

When cells or tissue age – called senescence – they lose the ability to regenerate and secrete certain proteins, like a distinctive fingerprint. One of those proteins, PAI-1 (plasminogen activator inhibitor) has been [a focus of] research, originally as it relates to cardiovascular disease. “We made the intellectual leap between a marker of senescence and physiological aging. We asked is this marker for cell aging one of the drivers or mechanisms of rapid physiological aging?”

For the study, [researchers] used mice bred to be deficient in a gene (Klotho) that suppresses aging. These mice exhibit accelerated aging in the form of arteriosclerosis, neurodegeneration, osteoporosis and emphysema and have much shorter life spans than regular mice. [These] rapidly aging mice produce increased levels of PAI-1 in their blood and tissue.

Then scientists fed the rapidly aging mice TM5441 – the experimental drug – in their food every day. The result was a decrease in PAI-1 activity, which quadrupled the mice’s life span and kept their organs healthy and functioning. “This is a completely different target and different drug than anything else being investigated for potential effects in prolonging life. It makes sense that this might be one component of a cocktail of drugs or supplements that a person might take in the future to extend their healthy life.”

Link: http://www.northwestern.edu/newscenter/stories/2014/04/experimental-drug-prolongs-life

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

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The Methuselah Mouse Prize: Changing the Conversation about Aging – Article by Advocate of Negligible Senescence

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The New Renaissance Hat
Advocate of Negligible Senescence
May 3, 2014
Recommend this page.
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ANS_Methuselah_Mouse_Prize
Methuselah Foundation created a stir in the research community by introducing the Methuselah Mouse Prize in 2003. The Mouse Prize was designed to directly accelerate the development of revolutionary new life extension therapies by awarding two cash prizes: one to the research team that broke the world record for the oldest-ever mouse; and one to the team that developed the most successful late-onset rejuvenation strategy.Unlike other engineering prizes (for example, the X Prize for lunar exploration), an award of the Methuselah Mouse Prize is not the end of the matter. The winner establishes a record that others have to break.
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Why mice? Mice are genetically similar to humans. They are small and inexpensive to maintain so studying large quantities is feasible. Their short lifespan, about three years, makes it possible to see if interventions result in longer, healthier lives—all in time to be of benefit to our own lives.

The Mouse Prize for longevity was first won by a team led by Dr. Andrzej Bartke of Southern Illinois University. The prize for rejuvenation first went to Dr. Stephen Spindler of the University of California.

Additionally, in 2009, the first Special Mprize Lifespan Achievement Award went to Dr. Z. Dave Sharp for the successful healthy life extension of already aged mice using a pharmaceutical, rapamycin.
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Through programs like the Methuselah Mouse Prize, Methuselah Foundation has helped change the conversation on aging and longevity, lending credibility and prestige to areas of research that once were openly frowned upon.
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Previous winners have already proven that healthy life can be extended; more wins are possible by researchers who can best previous winners’ performances, and each new winner pushes the outer limits of healthy life back even further.

How translatable the lesson of a Methuselah mouse will be to people is a matter of debate. The logic of disposable-soma theory applies to both species.

Private donations made since 2003 have bumped the prize value up to nearly $3.5 million, according to the latest update on the Methuselah Foundation website.

Don’t be misled by the size of the fund into thinking that a small donation will make no difference, because this is fundamentally a popular enterprise, a people’s prize, so the number of individual donors is really just as important as the total.

Searching for a cure for age-related ill health, a problem that kills more people than all other causes combined, is a moral imperative. The Advocate for Negligible Senescence publishes articles that discuss and educate the public about research to combat senescence. See the Advocate’s Facebook page.  

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Why Prioritize SENS Research for Human Longevity? – Article by Reason

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The New Renaissance Hat
Reason
December 29, 2013
Recommend this page.
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Why do I vocally support rejuvenation research based on the Strategies for Engineered Negligible Senescence (SENS) over other forms of longevity science? Why do I hold the view that SENS and SENS-like research should be prioritized and massively funded? The short answer to this question is that SENS-derived medical biotechnology has a much greater expected utility – it will most likely produce far better outcomes, and at a lower cost – than other presently ongoing lines of research into creating greater human longevity.

What is SENS?

But firstly, what is SENS? It is more an umbrella collection of categories than a specific program, though it is the case that narrowly focused SENS research initiatives run under the auspices of the SENS Research Foundation. On the science side of the house, SENS is a synthesis of existing knowledge from the broad mainstream position regarding aging and the diseases of aging: that aging is caused by a stochastic accumulation of damage at the level of cells and protein machinery in and around these cells. SENS is a proposal, based on recent decades of research, as to which of the identified forms of damage and change in old tissues are fundamental – i.e. which are direct byproducts of metabolic operation rather than cascading effects of other fundamental damage. On the development side of the house, SENS pulls together work from many subfields of medical research to show that there are clear and well-defined ways to produce therapies that can repair, reverse, or make irrelevant these fundamental forms of biological damage associated with aging.

(You can read about the various forms of low-level damage that cause aging at the SENS Research Foundation website and elsewhere. This list includes: mitochondrial DNA mutations; buildup of resilient waste products inside and around cells; growing numbers of senescent and other malfunctioning cells; loss of stem cells; and a few others).

Present arguments within the mainstream of aging research are largely over the relative importance of damage type A versus damage type B, and how exactly the extremely complex interaction of damage with metabolism progresses – but not what that damage actually is. A large fraction of modern funding for aging research goes towards building a greater understanding this progression; certainly more than goes towards actually doing anything about it. Here is the thing, however: while understanding the dynamics of damage in aging is very much a work in progress, the damage itself is well known. The research community can accurately enumerate the differences between old tissue and young tissue, or an old cell and a young cell – and it has been a good number of years since anything new was added to that list.

If you can repair the cellular damage that causes aging, it doesn’t matter how it happens or how it affects the organism when it’s there. This is the important realization for SENS – that much of the ongoing work of the aging research community is largely irrelevant if the goal is to get to human rejuvenation as rapidly as possible. Enough is already known of the likely causes of aging to have a reasonable expectation of being able to produce laboratory demonstrations of rejuvenation in animal models within a decade or two, given large-scale funding.

Comparing Expected Values

Expected value drives human endeavor. What path ahead do we expect to produce the greatest gain? In longevity science the investment is concretely measured in money and time, and we might think of the expected value in terms of years of healthy life added by the resulting therapies. The cost of these therapies really isn’t much of a factor – all major medical procedures and other therapies tend to converge to similar costs over time, based on their category: consider a surgery versus an infusion versus a course of pills, for example, where it’s fairly obvious that the pricing derives from how much skilled labor is involved and how much care the patient requires as a direct result of the process.

On the input side, there are estimates for the cost in time and money to implement SENS therapies for laboratory mice. For the sake of keeping things simple, I’ll note that these oscillate around the figures of a billion dollars and ten years for the crash program of fully-funded research. A billion dollars is about the yearly budget of the NIA these days, give or take, which might be a third of all research funding directed towards aging – by some estimates, anyway, though this is a very hard figure to verify in any way. It’s by no means certain the that the general one-third/two-thirds split between government and private research funding extends to aging research.

On the output side, early SENS implementations would be expected to take an old mouse and double its remaining life expectancy – e.g. produce actual rejuvenation, actual repair, and reversal of the low-level damage that causes aging, with repeated applications at intervals producing diminishing but still measurable further gains. This is the thing about a rejuvenation therapy that works; you can keep on applying it to sweep up newly accruing damage.

So what other longevity science do we have to compare against? The only large running programs are those that have grown out of the search for calorie-restriction mimetic drugs. So there is the past decade or so of research into sirtuins, and there is growing interest in mTOR and rapamycin analogs that looks to be more of the same, but slightly better (though that is a low bar to clear).

In the case of sirtuins, money has certainly flowed. Sirtris itself sold for ~$700 million, and it’s probably not unreasonable to suggest that a billion dollars have gone into broader sirtuin-related research and development over the past decade. What does the research community have to show for that? Basically nothing other than an increased understanding of some aspects of metabolism relating to calorie restriction and other adaptations that alter lifespan in response to environmental circumstances. Certainly no mice living longer in widely replicated studies as is the case for mTOR and rapamycin – the sirtuin results and underlying science are still much debated, much in dispute.

The historical ratio of dollars to results for any sort of way to manipulate our metabolism to slow aging is exceedingly poor. The thing is, this ratio shouldn’t be expected to get all that much better. Even if marvelously successful, the best possible realistic end result of a drug that slows aging based on what is known today – say something that extracts the best side of mTOR manipulation with none of the side-effects of rapamycin – is a very modest gain in human longevity. It can’t greatly repair or reverse existing damage, it can’t much help those who are already old become less damaged, it will likely not even be as effective as actual, old-fashioned calorie restriction. The current consensus is that calorie restriction itself is not going to add more than a few years to a human life – though it certainly has impressive health benefits.

(A sidebar: we can hope that one thing that ultimately emerges from all this research is an explanation as to how humans can enjoy such large health benefits from calorie restriction, commensurate with those seen in animals such as mice, without also gaining longer lives to match. But if just eating fewer calories while obtaining good nutrition could make humans reliably live 40% longer, I think that would have been noted at some point in the last few thousand years, or at least certainly in the last few hundred).

From this perspective, traditional drug research turned into longevity science looks like a long, slow slog to nowhere. It keeps people working, but to what end? Not producing significant results in extending human longevity, that’s for sure.

Ergo…

The cost of demonstrating that SENS is the right path or the wrong path – i.e. that aging is simply an accumulation of damage, and the many disparate research results making up the SENS vision are largely correct about which forms of change in aged tissue are the fundamental forms of damage that cause aging – is tiny compared to the cost of trying to safely eke out modest reductions in the pace of aging by manipulating metabolism via sirtuins or mTOR.

The end result of implementing SENS is true rejuvenation if aging is caused by damage: actual repair, actual reversal of aging. The end result of spending the same money and time on trying to manipulate metabolism to slow aging can already be observed in sirtuin research, and can reasonably be expected to be much the same the next time around the block with mTOR – it produces new knowledge and little else of concrete use, and even when it does eventually produce a drug candidate, it will likely be the case that you could do better yourself by simply practicing calorie restriction.

The expectation value of SENS is much greater than that of trying to slow aging via the traditional drug-discovery and development industry. Ergo the research and development community should be implementing SENS. It conforms to the consensus position on what causes aging, it costs far less than all other proposed interventions into the aging process, and the potential payoff is much greater.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 

This work is reproduced here in accord with a Creative Commons Attribution license.  It was originally published on FightAging.org.

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Support the “Little Mouse” Crowdfunded Life-Extension Research Project! – Post by G. Stolyarov II

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The New Renaissance Hat
G. Stolyarov II
October 4, 2013
Recommend this page.
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As part of my escalating efforts to advance the prospects of radical life extension through my individual actions, I have donated $50 to an ambitious new crowdfunding project to research longevity-enhancing treatments in mice.

This international project, undertaken by researchers at the Kiev Institute of Gerontology and supported by the Methuselah Foundation and the SENS Research Foundation, has an Indiegogo fundraising page, titled “I am a little mouse and I want to live longer!”, where contributions can be made.

I am proud to donate to this effort to support longevity research through crowdfunding. This project allows those of us who seek longer lifespans, and who wish to advance the science that will get us there, to contribute directly in a manner whereby each of us can make a sizable fraction of the difference for this research effort. I look forward to the great work that this project will accomplish. Achieving statistically significant mouse life extension in the near future could trigger massive public interest and the influx of major research funds to attain increasingly ambitious life-extension goals in higher-order mammals, culminating in us.

The project has already raised $8,673 and has 16 days remaining to reach its $15,000 goal. The Methuselah Foundation will match each $1,000 given with an equivalent donation – so it is possible to double one’s impact by contributing funds to this research effort.