Fight Aging! Newsletter, October 5th 2015

October 5th 2015

Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more.

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  • Launching the Fight Aging! 2015 125,000 Matching Fundraiser for SENS Rejuvenation Research
  • More Evidence for Higher Amino Acid Intakes to Slightly Soften Some of the Consequences of Aging
  • A Selection of Recent Alzheimer's Research
  • The WHO Vision: Do Something About Aging, But Without Doing Anything About Aging
  • Panel Discussion: How Can Life Extension Become as Popular as the War on Cancer?
  • Latest Headlines from Fight Aging!
    • Comparative Biology of Aging at the Austad Lab
    • #LifespanChallenge Starts on October 1st
    • A Trial of Embryonic Stem Cells to Treat Macular Degeneration
    • Aging Science Comes of Age
    • Considering Cross-Linking Within a Single Extracellular Matrix Collagen Molecule
    • Success for Mitochondrial Repair Crowdfunding Project
    • Domestic Dogs as a Natural Disease Model for Aging Research
    • Incoherent Fears of Unequal Access to Longevity Science
    • BioViva Moving Ahead With Human Gene Therapy for Telomerase Activation
    • Mitochondrial Catalase Suppresses Cancer Incidence in Mice


Today I'm pleased to announce the launch of this year's Fight Aging! matching fundraiser in support of the work of the SENS Research Foundation, funding scientific programs to speed progress towards working rejuvenation therapies and an end to frailty and disease in aging. In 2013 we raised 60,000, in 2014 150,000, and this year we're shooting at a cool quarter of a millio. You never know where the limits really are unless you forge ahead, and support for the treatment of aging as a medical condition is growing more rapidly today than at any time since the creation of Fight Aging!

We have kicked things off with a Reddit /r/futurology post this year, as we did last year. Please do take a look and share the link and this fundraiser with those who might appreciate it. The /r/futurology community has been a great help in the past, and a source of many new supporters of longevity science.

Front and center, I'd like to thank Josh Triplett, Christophe and Dominique Cornuejols, Michael Greve of, and Stefan Richter for joining Fight Aging! in putting money on the table to set up a 125,000 matching fund for this event. From today until December 31st 2015, we will match every donation to the SENS Research Foundation. I'd also like to thank David Gobel at the Methuselah Foundation for leaping in to be the first donor, providing an additional 15,000 for SENS research this year. Only another 110,000 to go, and three months to do it in!

How do we create a real, actual medical rejuvenation industry? By building technologies capable of repairing the known forms of cellular and molecular damage that cause aging. These types of damage are well-cataloged, and there is broad consensus on their relevance to age-related disease, but surprisingly little work takes place in the research community when it comes to making use of this knowledge to create treatments. This is even more surprising given that where progress has been made, such in amyloid clearance, senescent cell clearance, and mitochondrial repair, even early stage outcomes are of great quality, and clearly well worth further attention.

Funding for SENS technologies has been underway at a modest level for a decade now, and I can point to concrete progress occurring as a result. The wheel is starting to turn, and prospective SENS and SENS-like damage repair treatments targeting the causes of aging are beginning to leave the labs for clinical translation. Our community created this achievement, through advocacy and a comparatively small amount of funding directed to speed and enable to most promising scientific programs. One of the great secrets of our age is that early stage research is very cheap, but next to no-one other than philanthropists is willing to fund it. Just as soon as a prototype can be built, however, other institutions flock to fund the next stages. When looking at this is seems pretty clear that creating new and far more effective medical technologies really does fall upon the shoulders of the average person with a little vision, and the willingness to stand up and make a difference.

For example, all of these growing lines of development were originally seeded by small amounts of funding at critical times over the past decade, all of it provided by philanthropic donations. You can find further details in the latest SENS Research Foundation annual report.

Firstly: from 2008, donors to the Methuselah Foundation and then SENS Research Foundation collectively helped fund the work of the Marisol Corral-Debrinski lab on allotopic expression of mitochondrial genes, a way to rescue cells in aging tissues from mitochondrial DNA damage. That was successful and in the years since then these researchers founded, grew, and found venture funding for Gensight, a company that is now devoting tens of millions to establishing the first clinical trials of this technology for inherited mitochondrial disease. Yet without the funding at the earliest stage, provided by forward-thinking SENS supporters, that early stage work struggled to find a patron. This is the sort of difference that we can make.

Secondly: The SENS Research Foundation has for years been using donor funds to support efforts to clear senescent cells from tissues, to remove their insidious contribution to the aging process. In 2015 the Methuselah Foundation and SENS Research Foundation have provided seed funding for the startup company Oisin Biotech that will be further developing one of these methodologies: these clearance technologies are leaving the lab and starting on their own journey to the clinic, one that will see them attract far greater funding. But again, without the years of low-level philanthropy, these are projects that languished unfunded by the institutional research establishment in their early stages.

Thirdly: One of the first and longest-running SENS programs was aimed at clearing age-related chemical junk from the cellular recycling organelles called lysosomes. With age, these organelles become clogged and faulty, and cells drown in garbage and broken components. The SENS Research Foundation has produced drug candidate molecules from studies of bacteria known to consume these compounds, and the long-time supporter Jason Hope has founded Human Rejuvenation Technologies to develop the first round of treatments based on this technology, aimed initially at removing the characteristic blood vessel plaques of atherosclerosis.

This is how the world is changed, a weight of small decisions to help, snowballing into significant projects. This is how, step by step, we can build a near future in which being old isn't accompanied by pain, suffering, disease, and death.


One of the interesting minor themes to arise from the modern study of the biochemistry of aging is that aging is accompanied by numerous subtle, detrimental changes in the processing of dietary amino acids, both essential amino acids that cannot be constructed by human cellular biology, and the others that can, but which are also obtained from the diet. Here I'll point out recent research into an age-related decline in a process that consumes the amino acid cysteine, but there have been others over the years.

One such decline discovered some years back is that a growing failure to process the essential amino acid leucine is perhaps linked to loss of muscle mass with age, a condition known as sarcopenia, possibly via a chain of issues that upsets the balance between mechanisms breaking down muscle proteins and mechanisms assembling them. This can be overcome to at least some degree by throwing more leucine at the problem: there is evidence for leucine supplementation in older adults to have some impact on outcomes. There are numerous publications on this topic from the past decade or more, but the full details of what it actually going on and why - and especially the nature of the root causes - remain to be firmly pinned down, and the evidence itself is not undisputed. That is the story at present for most of these fine details in the corner of the bigger picture.

This is especially interesting for those of us who practice some form of calorie restriction or protein restriction with the aim of methionine restriction. Low levels of the essential amino acid methionine seems to be the key trigger for much of the beneficial metabolic alteration that occurs in response to calorie restriction. Studies in mice show that life-long restriction in fact blunts sarcopenia. Yet here is another set of evidence to suggest that more of at least some constituents of protein has much the same effect. It is a reminder that outcomes in health and aging are many up of many strands.

The paper linked below presents a fairly similar situation to that of leucine and sarcopenia, but for cysteine and the production of cellular antioxidants necessary for the proper function of metabolism. Again there is some ability to overcome the issue by delivering more cysteine in the diet, perhaps a theme that might be repeated elsewhere in our biochemistry as well:

An increased need for dietary cysteine in support of glutathione synthesis may underlie the increased risk for mortality associated with low protein intake in the elderly

Restricted dietary intakes of protein or essential amino acids tend to slow aging and boost lifespan in rodents, presumably because they downregulate IGF-I/Akt/mTORC1 signaling that acts as a pacesetter for aging and promotes cancer induction. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III cohort has revealed that relatively low protein intakes in mid-life (under 10 % of calories) are indeed associated with decreased subsequent risk for mortality. However, in those over 65 at baseline, such low protein intakes were associated with increased risk for mortality. This finding accords well with other epidemiology correlating relatively high protein intakes with lower risk for loss of lean mass and bone density in the elderly. Increased efficiency of protein translation reflecting increased leucine intake and consequent greater mTORC1 activity may play a role in this effect; however, at present there is little solid evidence that leucine supplementation provides important long-term benefits to the elderly.

Aside from its potential pro-anabolic impact, higher dietary protein intakes may protect the elderly in another way-by providing increased amino acid substrate for synthesis of key protective factors. There is growing evidence, in both rodents and humans, that glutathione synthesis declines with increasing age, likely reflecting diminished function of Nrf2-dependent inductive mechanisms that boost expression of glutamate cysteine ligase (GCL), rate-limiting for glutathione synthesis. Intracellular glutathione blunts the negative impact of reactive oxygen species (ROS) on cell health and functions both by acting as an oxidant scavenger and by opposing the pro-inflammatory influence of hydrogen peroxide on cell signaling.

Fortunately, since GCL's K m for cysteine is close to intracellular cysteine levels, increased intakes of cysteine - achieved from whole proteins or via supplementation with N-acetylcysteine (NAC) - can achieve a compensatory increase in glutathione synthesis, such that more youthful tissue levels of this compound can be restored. Supplementation with phase 2 inducers - such as lipoic acid - can likewise increase glutathione levels by promoting increased GCL expression. In aging humans and/or rodents, NAC supplementation has exerted favorable effects on vascular health, muscle strength, bone density, cell-mediated immunity, markers of systemic inflammation, preservation of cognitive function, progression of neurodegeneration, and the clinical course of influenza - effects which could be expected to lessen mortality and stave off frailty.

Hence, greater cysteine availability may explain much of the favorable impact of higher protein intakes on mortality and frailty risk in the elderly, and joint supplementation with NAC and lipoic acid could be notably protective in the elderly, particularly in those who follow plant-based diets relatively low in protein. It is less clear whether the lower arginine intake associated with low-protein diets has an adverse impact on vascular health.

While interesting as a theme, all of this is still small potatoes in the grand scheme of things: a great deal of data boils down to small effects on long-term health. You cannot use diets and supplements to greatly alter the tiny odds of passing beyond 100 years of age in the environment of today's medical technology. This is true for much of the study of aging, with its primary focus on mapping the entirety of cellular metabolism and its changes over time, rather than on the production of far more effective treatments. A different approach to the problem is required for meaningful progress towards greater healthy longevity, a focus on repair of the known root causes of aging, on the actual treatment of aging rather than continued investigation of the fine details of how aging progresses when left untreated, or how to tinker a little more function out of a damaged biochemistry. Repair is the way forward, aiming to reverse the damage, as exemplified by the SENS rejuvenation research programs.


Alzheimer's disease is becoming a well-known age-related condition, something that the average fellow in the street has actually heard of, unlike the vast majority of unpleasant things that happen to people as their bodies fail due to the accumulation of cell and tissue damage that causes aging. The widespread awareness of Alzheimer's disease is a function of the large-scale funding for research into its mechanisms; half of the National Institute on Aging budget is focused on this condition and all that needs to be learned to treat it effectively, and a correspondingly large chunk of private funding for neuroscience and the development of therapies for neurodegeneration is aimed in the same general direction.

We might think that Alzheimer's occupies the role of figurehead or rallying flag, a way to draw funds to the principal scientific goal of complete understanding of the biochemistry of the brain. This tends to be how things happen for large scale funding in medicine; three decades ago AIDS had much the same relationship with the broadest extent of viral research aimed at understanding first and therapies second. As is the case for Alzheimer's, it was an overlap of new capabilities in biotechnology, the existence of an effective advocacy community, and the need for funding to push forward the frontiers of scientific knowledge: numerous self-interests coming together.

Below you'll find links to a selection of recent Alzheimer's research. There is a lot going on, as it is a very complex condition, and the study of Alzheimer's really is the study of a very large slice of the biochemistry of the brain as a whole. One of the defining features of the field at present is a divergence of theories and exploration of alternative possible mechanisms beyond the accumulation of amyloid in brain tissues and the direct consequences of higher amyloid levels, meaning the creation of toxic and damaging molecules and the death or dsyfunction of brain cells. This search for alternatives is prompted by years of ongoing difficulties in the production of amyloid clearance therapies. Theorizing and early stage research are very cheap in comparison to later stages of development, and so always race ahead whenever obstacles arise.

Something else to bear in mind when reading the research in this field is that Alzheimer's appears to be almost as much a lifestyle disease as type 2 diabetes, though without the option to turn back at even comparatively late stages via aggressive lifestyle changes and fasting. People who get Alzheimer's are largely those who have been overweight and sedentary for decades: the same risk factors as is the case for diabetes and cardiovascular disease, and many of the underlying mechanisms may overlap in these and other age-related conditions. The degree to which Alzheimer's is an inevitability regardless of good health practices given a long enough life is an interesting question: everyone seems to accumulate more amyloid with age, but in the case of the oldest human beings it isn't the types of amyloid in the brain that cause death.

Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer's disease

Amyloid-beta (Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). The physiological capacity of peripheral tissues and organs in clearing brain-derived Aβ and its therapeutic potential for AD remains largely unknown. Here, we measured blood Aβ levels in different locations of the circulation in humans and mice, and used a parabiosis model to investigate the effect of peripheral Aβ catabolism on AD pathogenesis.

Parabiosis before and after Aβ deposition in the brain significantly reduced brain Aβ burden without alterations in the expression of amyloid precursor protein, Aβ generating and degrading enzymes, Aβ transport receptors, and AD-type pathologies including hyperphosphorylated tau, neuroinflammation, as well as neuronal degeneration and loss in the brains of parabiotic AD mice. Our study revealed that the peripheral system is potent in clearing brain Aβ and preventing AD pathogenesis. The present work suggests that peripheral Aβ clearance is a valid therapeutic approach for AD, and implies that deficits in the Aβ clearance in the periphery might also contribute to AD pathogenesis.

Misframed ubiquitin and impaired protein quality control: an early event in Alzheimer's disease

Amyloid β (Aβ) plaque formation is a prominent cellular hallmark of Alzheimer's disease (AD). To date, immunization trials in AD patients have not been effective in terms of curing or ameliorating dementia. In addition, γ-secretase inhibitor strategies await clinical improvements in AD. These approaches were based upon the idea that autosomal dominant mutations in amyloid precursor protein (APP) and Presenilin 1 (PS1) genes are predictive for treatment of all AD patients. However most AD patients are of the sporadic form which partly explains the failures to treat this multifactorial disease.

Recently, pooled GWAS studies identified protein ubiquitination as one of the key modulators of AD. This revealed numerous proteins that strongly interact with ubiquitin (UBB) signaling, and pointing to a dysfunctional ubiquitin proteasome system (UPS) as a causal factor in AD. We reported that DNA-RNA sequence differences in several genes including ubiquitin do occur in AD, the resulting misframed protein of which accumulates in the neurofibrillary tangles (NFTs). This suggests again a functional link between neurodegeneration of the AD type and loss of protein quality control by the UPS.

Vascular pathology: Cause or effect in Alzheimer disease?

The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead to neuronal damage and dementia. Destruction of the organisation of the blood brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context would thus be responsible for any subsequent neuronal damage since these factors promote aggregation of β-amyloid peptide in the brain. It is difficult to determine whether the vascular component in AD is the cause or the effect of the disease, but there is no doubt that vascular pathology has an important relationship with AD. Vascular dysfunction is likely to act synergistically with neurodegenerative changes in a cycle that exacerbates the cognitive impairment found in AD.

Overestimating the Effects of Healthy Aging

As models of preclinical AD continue to develop, a challenge to the field is to reconcile the evidence of AD-related pathology found in a large number of cognitively normal (CN) elderly people with the notion of "healthy" or "successful" aging. This evidence seems to question the research practice of not considering possible presence of Alzheimer's pathology in CN elderly participants when including healthy elderly persons in cognitive studies. However, without the actual evidence to exclude Alzheimer's pathology, one can assume that some percentage of CN elderly subjects in such studies may represent preclinical AD. This problem has been occasionally recognized. It clearly requires a systematic change in approach, because subtle cognitive changes, reliance on cognitive strategies, and networks' reorganization that one would interpret as the effects of healthy aging might actually reflect the disease progression.

Vasculoprotection as a Convergent, Multi-Targeted Mechanism of Anti-AD Therapeutics and Interventions

In the wake of failed amyloid-targeted drug trials and immune therapies, recent efforts are directed towards a broad range of alternative mechanisms of AD including mitochondrial dysfunction, metabolic stress, altered insulin signaling and, related to the 'vascular hypothesis of AD', cerebrovascular dysfunction. Accumulating evidence in fact supports the notion that cerebro- or neurovascular dysfunction may represent a primary initiator of a cascade of pathogenic events leading to neurodegeneration in AD. This mechanism takes on added significance when one considers increasing evidence linking sporadic AD with a number of vascular disorders including hypertension, hypercholesterolemia, obesity and type 2-diabetes.

Can oral infection be a risk factor for Alzheimer's disease?

Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology. Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (herpes simplex type I), and yeasts (Candida species). A causal relationship between periodontal pathogens and non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links. Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteremias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia.

Promising results with inhibitors of amyloid formation

When proteins change their structure and clump together, formation of amyloid fibrils and plaques may occur. Such "misfolding" and "protein aggregation" processes damage cells and cause diseases such as Alzheimer's and type 2 diabetes. A team of scientists have now developed molecules that suppress protein aggregation and could pave the way for new treatments to combat Alzheimer's, type 2 diabetes and other cell-degenerative diseases. The scientists designed and studied 16 different peptide molecules in order to find out which of them are able to impede the cytotoxic "clumping" of the proteins amyloid beta (Aß) and islet amyloid polypeptide (IAPP), which are associated with Alzheimer's and type 2 diabetes.

IV Administration of Endothelin B Receptor Drug Reduces Memory Loss, Oxidative Stress in Alzheimer's Disease

"We used the novel approach of stimulating the endothelin B receptors by intravenous injection of IRL-1620 to prevent and repair the damage to the brain caused by Alzheimer's disease. Rats with AD showed impaired learning and memory and increased oxidative stress. We found that treatment with IRL-1620 reversed these effects. Intravenous injection with the drug improved memory deficit by 50 to 60 percent and reduced oxidative stress by 45 to 50 percent. We also found that treatment with IRL-1620 enhanced certain recovery processes within the AD-damaged brain, resulting in more new blood vessels and neuronal cells. This indicates reparative processes occurring in the damaged brain."


The average age of populations around the world is rising: improved medicine and greater wealth leads to increased longevity and lower population growth at the same time. The number of old people is rising rapidly, and this at a time when technologies for treating aging as a medical condition are just around the corner, given sufficient funding and support. The World Health Organization (WHO) recently released their report on aging and health for 2015, and I have to say it makes for very strange reading. You might find the exexcutive summary (PDF) easier going than the full report (PDF). As I worked my way through the summary, I became increasingly incredulous that at no point in the document was medical research discussed. Not a single mention. This stands out as an exceptional omission in an otherwise sensible and coherent position statement. Take this for example:

The changes that constitute and influence ageing are complex. At the biological level, ageing is associated with the accumulation of a wide variety of molecular and cellular damage. Over time, this damage leads to a gradual decrease in physiological reserves, an increased risk of many diseases and a general decline in the intrinsic capacity of the individual. Ultimately, it results in death. But these changes are neither linear nor consistent, and they are only loosely associated with a person's age in years.

This report defines Healthy Ageing as the process of developing and maintaining the functional ability that enables wellbeing in older age. Central to this conceptualization of Healthy Ageing is an understanding that neither intrinsic capacity nor functional ability remains constant. Although both tend to decline with increasing age, life choices or interventions at different points during the life course will determine the path - or trajectory - of each individual.

Yet at every point in the report where technological progress in medicine might be mentioned, there is silence on this topic. Where lists are provided of ways to help people retain functional ability as they age, they focus on compensation for disability, on lifestyle choices, on greater availability of services for the elderly, but say nothing on the improvement of therapies to treat aging and age-related conditions. In fact, right up front in the preamble you can find this:

The report aims to move the debate about the most appropriate public health response to population ageing into new - and much broader - territory. The overarching message is optimistic: with the right policies and services in place, population ageing can be viewed as a rich new opportunity for both individuals and societies. The resulting framework for taking public health action offers a menu of concrete steps that can be adapted for use in countries at all levels of economic development.

In setting out this framework, the report emphasizes that healthy ageing is more than just the absence of disease. For most older people, the maintenance of functional ability has the highest importance. The greatest costs to society are not the expenditures made to foster this functional ability, but the benefits that might be missed if we fail to make the appropriate adaptations and investments. The recommended societal approach to population ageing, which includes the goal of building an age-friendly world, requires a transformation of health systems away from disease-based curative models and towards the provision of integrated care that is centred on the needs of older people.

In the context of the report as a whole, I read this as "more coping, less medicine." This seems like well-spoken insanity to me. You can't talk about age-related frailty and disability outside the context of medical research into aging and the development of new and better therapies. You can't herald a world in which growing numbers of people are living longer without talking about the ongoing advances in medicine that have enabled this outcome. Yet here is this policy document, doing just that. Calling for greater accommodation of the consequences of aging while ignoring medical science and the great rate of change in biotechnology is perhaps a manifestation of the instinct to conservatism in all political bodies: the urge to see stasis in the world, even against all the evidence, even in an age of rapid, accelerating progress. Only within a worldview in which aging is set in stone, never to be changed, can this document make any sense to anyone. Yet it clearly acknowledges change throughout, in every other aspect.

In any case, I stand amazed at this output of the bureaucratic process.


Given the BioViva press release I pointed out earlier today, you may be interested in listening to a Longevity Day roundtable held yesterday, since Elizabeth Parrish of BioViva was participating, as well as Keith Comito of the Life Extension Advocacy Foundation, and a few other names you might recognize. From my perspective it is great to see so much going on that I only find out about after the fact: one of the signs of a healthy and growing community is that people are off doing things and I have no idea, since there is too much to keep track of in any reasonable amount of time.

What can be done to raise public support for the pursuit of indefinite life extension through medicine and biotechnology to the same level as currently exists for disease-specific research efforts aimed at cancers, heart disease, ALS, and similar large-scale nemeses? In this panel discussion, held on October 1, 2015 - International Longevity Day - Mr. Stolyarov asks notable life-extension supporters to provide input on this vital question and related areas relevant to accelerating the pursuit of indefinite longevity. This panel is coordinated in conjunction with MILE, the Movement for Indefinite Life Extension.

Panelists: Adam Alonzi, Sven Bulterjis, Keith Comito, Roen Horn, B. J. Murphy, and Elizabeth Parrish

A set of presentation slides was put together by Butlerjis, and is worth a few minutes of your time. In particular, one of the lessons to take away here is that big budget cancer research didn't just magically happen overnight. Rather it was the culmination of many failed attempts to create such a state of affairs over the course of half a century. Prior to the 1970s cancer research in fact looked quite similar to the situation for aging research today: little interest, little funding, large gaps in the scientific understanding of the fine details of the disease, but the clear potential to make a big difference to patients and therapies with what was known at the time.

Aging Research Needs Marketing: What Can We Learn from Cancer Research?

1910: The American Association for Cancer Research convinces president Taft to ask congress to build a national lab for cancer research: failure.

1927: Senator Matthew Neely asks congress to give 5 million for information that could lead to a cure for cancer: he got 50,000.

1937: Neely, Senator Homer Bone and Representative Warren Magnuson : National Cancer Institute Act, success signed by president Roosevelt: NCI founded, but the war in Europe soon ended funds for the NCI.

1946-47: Neely and Senator Claude Pepper: 3rd proposal for nation wide cancer research: rejected.

Solomon Garb said in 1969: "A big obstacle in the fight against cancer is the severe an chronic lack of money, something that is not known to most people. We won't get there by repeating this. It is also necessary to explain how it will be used, what kind of projects will be financed with it, why these projects deserve our support, and where the scientists and technicians that have to execute them will come from."

Why do some diseases have a big impact only in a given era? Theory: the society couples diseases to psychological crises. For Cancer: in the '70s when the focus changed from external (USSR) to internal (cancer). For AIDS: in the '80s when the generation was obsessed with sexuality and freedom. For SARS: in the 21st century alongside the fears of globalization. But what about aging?

To conclude: cancer has a similar history to aging, we also need marketing, business people, and celebrities on our side, and aging has to be recognized as a disease.


Monday, September 28, 2015

This article provides a short overview of the work on comparative biology of aging taking place at the laboratory of Steven Austad:

The longest-lived human on record didn't make it much past 120 years. That's nothing compared to the ocean quahog, a fist-sized clam found off the coast of Maine. "They can live 500 years or longer. They've been sitting out there on the sea floor since before Shakespeare was born." Steven Austad's research focuses on understanding the underlying causes of aging at the molecular level. Although his studies take him in many fascinating directions, it's the ancient clams that everyone remembers. So what do animals like the quahog know about healthy aging that we don't? That question drives Austad's studies in comparative gerontology, which look to long-lived animals to identify new molecular targets to help humans.

Clams - technically, bivalve mollusks - live longer than any other animal group; more than a dozen species have lifespans of a century or more. But they are not all masters of aging. Austad's lab is studying mitochondrial function, protein stability and stress resistance across seven species of clams, with lifespans ranging from one year to the ocean quahog's 500-plus years. Austad's research has convinced him that one key to slowing aging is to protect the proteins inside our cells. "Proteins make everything work in the cell, and to do that, they have to be folded precisely like origami. But as we get older they get battered about, and ultimately lose that precise shape. Quahogs, unlike us, keep their proteins in shape century after century." When Austad takes human proteins and adds them to a mix of tissues from the clams, "they become more stable, less likely to unfold." His lab is now working to identify exactly what is protecting the clams' proteins. That mechanism could point to a potential treatment for aging, along with new therapies for Alzheimer's disease and other conditions caused by protein misfolding.

Monday, September 28, 2015

Staff at the longevity research crowdfunding site are launching their #LifespanChallenge event this Thursday October 1st. This is also the day on which this year's Fight Aging! matching fundraiser in support of SENS rejuvenation research kicks off, as well as being the date for numerous other events related to research into human longevity organized by the advocacy community:

Over the past few years there has been a tradition emerging of longevity researchers and activists around the world organizing events on or around October 1 - the UN International Day of Older Persons, or Longevity Day. This is an excellent idea, and to take it further will be running a social challenge campaign, not unlike the Ice Bucket Challenge, to raise both funds and awareness for life extension research - the #LifespanChallenge. It will begin on October 1 and run through the month of October.

1) Donate any amount via to a running campaign or to the Life Extension Advocacy Foundation (LEAF). If you have already done so already, feel free to skip to the next step.

2) Post a short video (or image with description) on social media where you are holding up the #LifespanChallenge sign (which you can print or show on a tablet, etc.). Share a personal reason why you sincerely care about life extension, or express yourself in any way that is linked to this theme.

3) Challenge 3 friends to do the above as well. Add a post description similar to this: "Hey everyone; here is my response to the #LifespanChallenge to help extend healthy lifespan! My reason for helping this cause is _____. If you want to help please donate any amount to or projects at, make a video like this, and challenge 3 of your friends to do the same. For example @FriendName1, @FriendName2, @FriendName3 I challenge you!"

Facebook has made it easy to upload video directly, so all you should need is a cell phone camera. The text that accompanies your post should be informative, tagging your friends (preface their name with an @ in Facebook, for example) and including the hashtag #LifespanChallenge. This will make the post visible to your friends and easy to find later. One of the goals of this challenge is to introduce more people to the idea of life extension, so make it a point to talk to at least one friend who is not already part of the life extension community about the #LifespanChallenge, and open up a dialogue around this topic.
Don't wait to be challenged; be a part of the first wave and help really get the ball rolling.

That's it! Let's keep up the momentum to #CrowdfundTheCure, and I hope you all have an excellent Longevity Day.

Tuesday, September 29, 2015

A trial is underway to test the use of embryonic stem cells as a treatment for the wet form of age-related macular degeneration, a conditional characterized by the structural damage and resulting blindness caused by excessive blood vessel growth into the retina:

Surgeons in London have carried out a pioneering human embryonic stem cell operation in an ongoing trial to find a cure for blindness for many patients. The procedure was performed on a woman aged 60 and involved "seeding" a tiny patch with specialised eye cells and implanting it at the back of the retina. The London Project to Cure Blindness was established a decade ago to try to reverse vision loss in patients with age-related macular degeneration (AMD). Ten patients with the wet form of AMD will undergo the procedure. All will have suffered a sudden loss of vision as a result of defective blood vessels in the eye. They will be monitored for a year to check that the treatment is safe and whether their vision improves.

The woman who was the patient had the operation last month. "We won't know until at least Christmas how good her vision is and how long that may be maintained, but we can see the cells are there under the retina where they should be and they appear to be healthy." The cells being used form the retinal pigment epithelium (RPE) - the layer of cells that nourish and support the photoreceptors in the macula - the seeing part of the eye. "This is truly a regenerative project. In the past it's been impossible to replace lost neural cells. If we can deliver the very layer of cells that is missing and give them their function back this would be of enormous benefit to people with the sight-threatening condition".

Tuesday, September 29, 2015

Here is a mainstream view of the growth in interest in aging research, a focus on discovery of how exactly aging progresses in fine detail and how that progression is influenced by environment and genes, and no mention of doing more than slightly altering the pace of aging. Growth in the field is ultimately a good thing, however, as at some point in the near future the disruptive approach of damage repair typified by the SENS programs, aiming for rejuvenation treatments that can reverse the progression of age-related degeneration, will produce practical results that are indisputably far better and far cheaper than those emerging from drug development to modestly slow aging. The more researchers available to move over to that line of work once persuaded, the better off we all are.

Aging is at the center of many of the world's most prevalent and deadly diseases, including cancer and heart disease. Over the last 20 years we have seen amazing advances in our understating of the mechanisms behind aging-related processes at the level of genes, cells and whole organisms. Many countries are now facing a growing aging society, with a high prevalence of fatal age-related diseases, such as cancer, cardiovascular, and pulmonary disease.

Exciting new lines of research have shown that aging involves a complex interplay between the genome, epigenome, microbiome, and the environment. Recent work on epigenetic modifications, the chemical signatures branded on our genome that affect gene expression, has revealed surprising links to the aging process and established a connection with environmental factors. Important epigenetic marks such as the methylation of regulatory DNA sequences, covalent modifications of histone proteins, and the expression of regulatory non-coding RNAs are affected during aging. The effect of the environment on this epigenetic landscape is clearly shown by studies using identical twins. As they age, these twins are no longer identical in their epigenome, showing differences in gene expression and ultimately, lifespan. Changes to the epigenetic landscape may affect gene expression and ultimately the aging process, especially through the modification of metabolism.

Food scarcity is one of the most important environmental factors affecting epigenetic modification; it is therefore not surprising that many molecules and signaling pathways that have been implicated in aging, such as mammalian target of rapamycin, sirtuins, and insulin-like growth factor/insulin signaling pathways, are related to metabolism. Thus, how our genes modify our metabolic status, depending on the food intake and consumption, is a central issue of aging science. Another new and exciting area in aging research involves the tiny microbes living in our bodies. Our gut, for example, hosts microorganisms that amount for 10 times as many cells than found in our body and 150 times as many genes as there are in our genome. Understanding the fundamental mechanisms of aging may lead to the development of new treatments that could be applicable to a wide variety of age-related diseases.

Wednesday, September 30, 2015

Here researchers suggest that cross-links in the extracellular matrix can be formed within single collagen molecules as well as between them, and that this can still degrade important properties of tissue. Cross-links form and are broken constantly in the extracellular matrix, consisting of many types of sugary by-products of metabolism. Some are far more resilient than others, and once formed tend to last for a long time. The structural properties of tissue are determined by the particular arrangement of molecules in the matrix, and when hardy forms of cross-link build up over the course of aging the result is loss of elasticity or strength. This is particularly noticeable in skin, but of much greater consequence in blood vessels, where stiffening causes hypertension and all of the cardiovascular dsyfunction that follows on from that.

In humans near all long-lived cross-links involve glucosepane, making clearance an attractive target for rejuvenation treatments, as only one class of compound must be broken down. Yet all too few groups are working on this. Those funded by the SENS Research Foundation might be the only people at the present time trying to build the basic tools needed to work with glucosepane in a cellular environment. It seems crazy to me that such obvious paths forward towards treating the common causes of age-related disease are widely ignored.

The extracellular matrix (ECM) undergoes progressive age-related stiffening and loss of proteolytic digestibility due to an increase in concentration of advanced glycation end products (AGEs). The most abundant AGE, glucosepane, accumulates in collagen with concentrations over 100 times greater than all other AGEs. Detrimental collagen stiffening properties are believed to play a significant role in several age-related diseases such as osteoporosis and cardiovascular disease.

Currently little is known of the potential location of covalently cross-linked glucosepane formation within collagen molecules; neither are there reports on how the respective cross-link sites affect the physical and biochemical properties of collagen. Using fully atomistic molecular dynamics simulations (MD) we have identified six sites where the formation of a covalent intra-molecular glucosepane cross-link within a single collagen molecule in a fibrillar environment is energetically favourable. Identification of these favourable sites enables us to align collagen cross-linking with experimentally observed changes to the ECM. For example, formation of glucosepane was found to be energetically favourable within close proximity of the Matrix Metalloproteinase-1 (MMP1) binding site, which could potentially disrupt collagen degradation.

Wednesday, September 30, 2015

The mitochondrial repair project being crowdfunded at has passed its original 30,000 goal, with nearly 300 people having donated to the cause. This is a solid start for the team, and I look forward to their future projects. One of the most important things that any of us can be doing - other than raising funds for research - is expanding the community, reaching out to find new supporters. Many of these donors have never given to this cause before, and the staff have been working hard on outreach these past few months. This should be becoming easier as the years pass and there is ever more incremental progress to show off thanks to past research, but bootstrapping a movement is hard work, a long slog. More hands and new approaches are always welcome. Meanwhile, on the research side, here are a few notes on the work that your generosity has enabled:

Reversing or preventing damage to mitochondrial DNA may be a key factor in slowing the aging process. At the SENS Research Foundation, we are in the early stages of creating an innovative system to repair these mitochondrial mutations. The MitoSENS team has already demonstrated the rescue of cells containing mitochondrial mutations, and has recently generated highly promising preliminary data showing the rescue of the complete loss of a mitochondrial gene. Our next steps will focus on improving the effectiveness of the targeting system, so that we can repeat our success with one mitochondrial gene to all thirteen. We will then transition this work into animal models of mitochondrial dysfunction. This would be a crucial step in what may be the development of an eventual cure for aging and aging related diseases.

We have a talented team of highly trained mitochondrial biologists working on MitoSENS. Right now the rate-limiting factor is the cost of the expensive reagents that we use for these experiments. Increasing our funding with this campaign will allow us to double the pace of our research and bring results to the public that much faster. We have made preliminary progress on rescuing function with a second gene, ATP6, and your support will help us perfect our targeting of both ATP8 and ATP6. This requires more cells, more viruses, and many new synthetic gene sequences. Specifically, we will spend your generous donations on cell culture reagents, oxygen consumption measurements, virus production, quantitative reverse transcription PCR, DNA synthesis services, and publication of our results in a peer-reviewed journal.

Thursday, October 1, 2015

Researchers here propose that the domestic dog population is overlooked as a cost-effective source of data on aging. It is certainly the case that there is a broad variation in life span as well as size between canine breeds, and comparative biology between and within species with disparate life spans is a strong thread in aging research these days:

With many caveats to the traditional vertebrate species pertaining to biogerontology investigations, it has been suggested that a most informative model is the one which: 1) examines closely related species, or various members of the same species with naturally occurring lifespan variation, 2) already has adequate medical procedures developed, 3) has a well annotated genome, 4) does not require artificial housing, and can live in its natural environment while being investigated, and 5) allows considerable information to be gathered within a relatively short period of time.

The domestic dog unsurprisingly fits each criterion mentioned. The dog has already become a key model system in which to evaluate surgical techniques and novel medications because of the remarkable similarity between human and canine conditions, treatments, and response to therapy. The dog naturally serves as a disease model for study, obviating the need to construct artificial genetically modified examples of disease. Just as the dog offers a natural model for human conditions and diseases, simple observation leads to the conclusion that the canine aging phenotype also mimics that of the human.

Genotype information, biochemical information pertaining to the GH/IGF-1 pathway, and some limited longitudinal investigations have begun the establishment of the domestic dog as a model of aging. Although we find that dogs indeed are a model to study aging and there are many independent pieces of canine aging data, there are many more "open" areas, ripe for investigation.

Thursday, October 1, 2015

There is something about the prospect of treating the causes of aging and greatly extending healthy life spans that makes otherwise sensible people throw common sense out of the window. If I had a dime for every time I saw incoherent predictions and conspiracy theories suggesting that rejuvenation therapies would be developed in secret and restricted to the wealthy elite, I'd have a lot of dimes. There is something ugly and irrational in human nature when it comes to this sort of topic.

In reality it is impossible to build new medical science in secret. It is impossible to build anything in secret that requires a community of tens of thousands, an entire supporting industry, global collaboration in research and development, and the active participation of the scientific community, relentlessly focused on papers and publication. The rejuvenation treatments that will result from from SENS-style repair approaches will be mass-produced infusions akin to biopharmaceutical medicines that today cost a few thousand for a course of treatment, administered by a bored clinician once every few years. After a couple of decades of market action they will be far less costly, like the older drugs produced today that are so cheap even the third world has access.

In short we all win together or we all lose together. This is a cooperative game, not a competitive one. This is all obvious and right in front of our noses; there are scores of examples in medicine today, demonstrating exactly how development and price works out over the years. Yet people are still willing to believe strange things about the future of treatments for aging, building castles of fearful fancy in the clouds.

Concerns about the advance of life extension science research and development frightens many people. Particularly, the level of private investment pouring into the industry. The most extreme of prophecies argue that there will be an absolute divide between the handful of super rich who can afford life extension treatments, and those who can't. The fear is that this divide will permit a world in which a new social order is established planted in financial wealth, but rooting from access to life-prolonging medicine.

Life extension science is at the forefront of this debate, with critics arguing that scientific research should be led by a social contract, rather than a fiscal objective. However, supporters believe that commercial input, especially in life extension, is accelerating the overall momentum of scientific research.

Ultimately though, life extension science is suffering from a complete lack of federal funding, and so if an anti-aging community is to be created, whether the result will benefit us all or just the richest in society, it must first be born out of big business and philanthropy. So then, if this is the case, how much truth and evidence are there in the claims from either side of the debate, and should we be afraid of private entities taking hold of the anti-aging industry?

Friday, October 2, 2015

BioViva is one of the small groups interested in bringing telomerase therapies to humans sooner rather than later. It seems they have started in on their small long-term trial of human gene therapy for telomerase activation, and have treated the first volunteer.

I should say that at any given time there is a fairly large gap between what can be done in human medicine, the technology that actually exists and works, and what is being done in trials. Most of this gap is due to regulation, and the rest of it because development groups want to have a reasonable certain that what they are doing actually works, does more good than harm, and so forth. The regulatory process might last a decade, while the actually useful part of that testing (does it basically work, and is the risk profile sufficiently defined and acceptable to patients) is only a few years. As the cost of research and development in the life sciences falls, it will become increasingly untenable that a huge ball and chain slows progress thanks to regulatory risk aversion, and a growing number of initiatives will forge ahead and build anyway. Some years ago I proposed the Vegas Group fable, something that I think will happen in the fullness of time: alternative roads that bypass official regulation in favor of faster progress, an inevitability in an environment of low-cost research. Also, I think, a necessity.

What about the science here? I've never been a big fan of telomere lengthening approaches, as average telomere length as it is measured today in immune cells looks very much like a marker of the progress of aging, an end stage consequence far removed from root causes. Telomeres shorten with cell division and new long-telomere cells are delivered into tissues by stem cell populations. Thus average telomere length in immune cells reflects some combination of immune health and stem cell activity, both of which are known to decline with age. You can't argue with the fact that telomerase gene therapy has been shown to extend life in mice, however, though you can certainly note that the size of the effect has been getting smaller as the research groups have refined their data and approaches.

How does this work to slow aging in mice? At this point I lump enhanced telomerase activity into the general category of approaches that either probably work or intend to work by boosting the activation of old stem cell populations, resulting in increased repair and tissue maintenance and thus a slower decline into frailty and organ failure. More telomerase doesn't seem to raise cancer risk in mice, but mice have very different telomere dynamics and cancer risk profiles than we humans. The fastest way to figure out what is going to happen in humans is of course to try it, and kudos to anyone volunteering at this stage, but I'd be waiting for a few more years of testing first in animal or tissue models closer to human telomere dynamics. In part that decision would be driven by the fact that I don't think that this is the best approach to move ahead with practical applications, to push ahead and get things done. I absolutely agree that pushing ahead to get things done needs to happen, but I'd rather see this sort of boldness for SENS treatments like senescent cell clearance.

BioViva USA, Inc. has become the first company to treat a person with gene therapy to reverse biological aging, using a combination of two therapies developed and applied outside the United States of America. Testing and research on these therapies is continuing in BioViva's affiliated labs worldwide. BioViva CEO Elizabeth Parrish announced that the subject is doing well and has resumed regular activities. Preliminary results will be evaluated at 5 and 8 months with full outcome expected at 12 months. The patient will then be monitored every year for 8 years.

Gene therapy allows doctors to treat disease at the cellular level by inserting a gene into a patient's cells instead of using the regular modalities of oral drugs or surgery. BioViva is testing several approaches to age reversal, including using gene therapy to introduce genes into the body. Although not generally considered a disease, cellular aging is the leading cause of death in the developed world. Side effects like muscle wasting (sarcopenia), grey hair and memory loss are the well-known hallmarks. And the aging cell is also responsible for the diseases of aging, including Alzheimer's disease, heart disease and cancer. BioViva is leading the charge to treat the aging cell and reverse aging. "The aging cell is a key factor that has been overlooked for too long. Companies have put millions into treating the diseases of aging, such as dementia, frailty, kidney failure and Parkinson's disease, and we still do not have a cure. Aging involves multiple pathways. We wanted to target more than one for a better outcome."

Friday, October 2, 2015

Gene therapy to raise levels of the natural antioxidant catalase in mitochondria is one of many methods shown to modestly extend life in mice. Cancer is so very prevalent in mice that it is frequently worth asking whether or not life extension is a matter of slowing aging or a matter of suppressing cancer - though there is certainly a lot of room for argument as to whether or not these are just two ways of stating the same thing, based on the details of the mechanisms involved. See the debate over whether rapamycin slows aging or suppresses cancer, for example. Given all this, the paper linked here is interesting:

The antioxidant enzyme catalase targeted to mitochondria (mCAT) has been shown to delay aging and cancer in mice, and the progression of transgenic oncogene and syngeneic tumors was suppressed, helping support the notion that attenuation of mitochondria-generated hydrogen peroxide signaling is associated with an antitumor effect.

In order to determine if mCAT has any effect on naturally occurring lung cancer of the adenocarcinoma type in old mice, the tumor incidence and progression were examined in the lungs of old mCAT transgenic and wild-type (WT) mice with a CB6F1 background. CB6F1 mice with a WT genotype were found to have a high incidence of adenomas at 24 months of age, which progressed to adenocarcinomas at 32 months of age. CB6F1 mice with the mCAT genotype had significantly reduced incidence and severity of lung tumors at both ages.

Fibroblasts isolated from the lungs of old mCAT mice, but not WT mice, were shown to secrete soluble factors that inhibited lung tumor cell growth suggesting that stromal fibroblasts play a role in mediating the antitumor effects of mCAT. The aged CB6F1 mouse, with its high incidence of K-ras mutant lung cancer, is an excellent model to further study the anticancer potential of mitochondria-targeted therapy.


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