Fight Aging! Newsletter, February 8th 2016

February 8th 2016

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.

This content is published under the Creative Commons Attribution 3.0 license. You are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

To subscribe or unsubscribe please visit: https://www.fightaging.org/newsletter/


  • What Next for Transthyretin Amyloid Clearance Therapies?
  • Recent Research on Muscles, Stem Cells, and Aging
  • 25% Median Life Extension in Mice via Senescent Cell Clearance, Unity Biotechnology Founded to Develop Therapies
  • Enhanced Proteasomal Activity Restores Declining Self-Renewal in Aging Neural Stem Cells
  • The SENS Rejuvenation Biotechnology Companies
  • Latest Headlines from Fight Aging!
    • FGF21 in Calorie Restriction Compared in Mice and Humans
    • 21st Century Medicine Mentioned in Scientific American
    • Model of Protein Charge Predicts Aging Associated Proteins
    • Proposing a Role for Acetylation in the Damage of Aging
    • On Developing a Stem Cell Therapy for Parkinson's Disease
    • Ampakine Prevents Loss of Dendrites in the Aging Rat Brain
    • Clearing Mitochondria Reverses Some Aspects of Cellular Senescence
    • Iron Oxide Nanoparticles Reduce Oxidative Stress in Flies
    • Towards Reversible Cryopreservation of Organs
    • Cytomegalovirus Associated with Cognitive Decline in Aging


If aging is damage, specific forms of cellular and molecular disarray, then rejuvenation is achieved through periodic repair of that damage. This is the Strategies for Engineered Negligible Senescence (SENS) vision for the future of treating aging, and it is a task that the medical research community is only just getting started on in any real way, sad to say. We are more than a decade in to advocacy and modest funding for SENS, and some progress has been achieved, however. Setting aside stem cell research and the amyloid clearing efforts of the Alzheimer's research community, as in both of those cases it is very hard to pick out the thin threads of rejuvenation biotechnology from other research that tries to compensate for damage or patch over damage, there are four SENS rejuvenation biotechnologies presently somewhere in the cusp between the laboratory and the clinic, in commercial development, and a fifth very close to that status.

Senescent cell clearance is achieved via several methods in rodents, and at least one company, Oisin Biotechnology, has been seed funded to bring such a therapy to market. Creating backup mitochondrial genes in the cell nucleus is still a matter of one gene at a time, but the technology to do that is at a comparatively advanced stage of commercial development at Gensight. Breaking down metabolic waste that contributes to atherosclerosis via the use of modified bacterial enzymes is an approach that recently moved from the SENS Research Foundation laboratories into development at Human Rejuvenation Technologies. The technology close to commercial development but not there yet is glucosepane cross-link clearance; based on recent discussions, it seems only a few years away from a viable drug candidate.

The topic for today, however, is transthyretin amyloid clearance, arguably the most advanced of the five SENS rejuvenation biotechnologies I've listed here. Amyloids are made up of misfolded proteins that in their damaged form precipitate from solution to form clumps and fibrils. There are a score of different types - the beta amyloid most people are familiar with, associated with Alzheimer's disease, is just one of them. In recent years, it has become clear that another type, transthyretin amyloid, is associated with heart failure, osteoarthritis, and a range of other conditions. In the oldest of humans, the small supercentenarian population, accumulation of transthyretin amyloid appears to be the predominant cause of death.

The small company Pentraxin signed up with GlaxoSmithKline back in 2009 to commercialize CPHPC as a treatment for transthyretin amyloidosis, a runaway version of the standard age-related accumulation of amyloid in which much more deposition occurs at a younger age, accompanied by organ failure and ultimately death. CPHPC works by clearing serum amyloid P component (SAP), a molecule associated with amyloid deposits and which seems to inhibit the normal processes of amyloid clearance. This therapy had been presented at the 4th SENS conference that same year. Like many lines of research in the Big Pharma world, this collaboration has moved forward only glacially since then, but it is moving. Along the way the use of CPHPC merged with another treatment based on the use of antibodies for SAP, and a small clinical trial of the combination therapy concluded with very positive results last year.

What next from here? At this point, a therapy exists that can, from a technical perspective, be deployed in humans with the expectation that it will clear meaningful amounts of transthyretin amyloid, with resulting improvement in the condition of patients. Unfortunately this is still very much locked up in the slow development processes at GSK, which most likely means years of trials yet, and no real urgency to move this out into the world. There is every reason to expect benefits to heart health over the long-term to result from periodic removal of transthyretin amyloid, and this is a technology I'd rather see widely used in clinics overseas, available via medical tourism, today, as opposed to being locked up behind closed regulatory doors. That outcome isn't in the GSK worldview, unfortunately, which means it will probably be an overly long time before these approaches reach the clinic. Meanwhile, diversification is a focus: finding more niches and potentially more lucrative niches in which to seek regulatory approval.

Pentraxin R&D Programmes

The single dose first in human study of anti-SAP antibodies co‑administered with CPHPC in patients with systemic amyloidosis remains currently underway. The initial results in the first 15 subjects to be treated have been accepted for publication and were be posted online in July 2015. The treatment has been safe and well tolerated so far and has produced unequivocal and unprecedented, swift and dramatic reduction in amyloid load, documented so far in the liver, spleen, kidneys and lymph nodes. Cardiac amyloidosis was excluded from the first part of the phase I study but subjects with cardiac involvement are now being treated.

Meanwhile alternative, novel immunotherapy approaches to treatment of amyloidosis are also being actively investigated. In a first clinical study of CPHPC in Alzheimer's disease we have shown that the drug safely and completely depletes SAP from the cerebrospinal fluid. We have now designed a comprehensive clinical trial of CPHPC in Alzheimer's disease, seeking evidence of disease modification and clinical efficacy. Preparation for and conduct of the 'Depletion of serum amyloid P component in Alzheimer's disease (DESPIAD) trial' is receiving substantial logistical and expert support from GSK and is being funded by the UCL/UCLH Biomedical Research Centre. It will start in 2016 and run to 2019.

There are alternative approaches to clearing transthyretin amyloidosis, such as the work on catalytic antibodies funded by the SENS Research Foundation. The expectation is that those, too, will be adopted by developers who set out to run the slow gauntlet of regulation, taking years longer than required for simple, sane considerations of safety and efficacy in order to get into the clinic. Even then therapies are only approved in a very limited way, and are made far more expensive by excessive regulatory costs. To my eyes the future needs much more of the distributed development and commercialization process that happened for stem cell medicine following the turn of the century, and is happening now for CRISPR gene therapies: many clinics offering services outside the restrictive regulation of the FDA and related agencies, building a market in which people can make their own informed choices on risk and early adoption, rather than being held back by the actions of self-serving, distant, and unaccountable bureaucrats.


Today I thought I'd point out a few recent papers and publicity materials on muscle aging. A large chunk of the research into stem cell aging and changes in cell metabolism with aging focus on muscle tissue. In part this is a feedback loop: the better understood models and types of cell are found in or associated with muscle tissue. Therefore more researchers use this as a starting point, and therefore the knowledge grows faster than is the case for other tissue types. It doesn't hurt that muscle tissue is easily sampled and examined in people and animals, unlike the cell populations of internal organs. That reduces the cost across the board for many types of study, and researchers are very conscious of cost - there is no such thing as a laboratory with enough funding for optimal progress. Measured by deeds rather than words, our society places very little value on medical research, or indeed research at all for that matter. The investment that goes into building the scientific understanding necessary to produce better medicine is minuscule in the grand scheme of things. Thus a core skill for any scientist to be able to do more with less, because less is absolutely the state of things.

Muscle mass and strength diminishes with aging. It is called sarcopenia in those who suffer this loss to a significantly greater degree, and there has been an ongoing effort for the past decade to formally define this condition within the US regulatory system. That this process is still underway, and with no end in sight, is a sign of just how much that system holds back progress. It thus remains illegal to try to commercialize therapies for sarcopenia, and that is felt all the way back down the chain of research and development in the form of reduced availability of funding. There are many mechanisms involved in muscle degeneration in aging, ranging from the characteristic reduction in stem cell activity in old tissues to the effects of chronic inflammation, passing through mitochondrial dysfunction and numerous other metabolic changes that impair aspects of muscle growth or operation. As is always the case, definitively linking the observed changes into lines of cause and consequence is a challenge. Clinics will be repairing aging with SENS rejuvenation therapies long before the research community can produce a comprehensive, detailed model of aging that traces every step from fundamental damage through to final end stage of disease.

You may find the research linked here interesting, but remember that it's a thin slice of a large and diverse selection of scientific initiatives. These are small snapshots in an evolving album relating to muscle aging, and that in turn is but a small part of the larger field.

Regenerating damaged muscle after a heart attack

Researchers used human embryonic stem cells to create a kind of cell, called a cardiac mesoderm cell, which has the ability to turn into cardiomyocytes, fibroblasts, smooth muscle, and endothelial cells. All these types of cells play an important role in helping repair a damaged heart. As those embryonic cells were in the process of changing into cardiac mesoderms, the team was able to identify two key markers on the cell surface. The markers, called CD13 and ROR2, pinpointed the cells that were likely to be the most efficient at changing into the kind of cells needed to repair damaged heart tissue. The researchers then transplanted those cells into an animal model and found that not only did many of the cells survive but they also produced the cells needed to regenerate heart muscle and vessels.

"In a major heart attack, a person loses an estimated 1 billion heart cells, which results in permanent scar tissue in the heart muscle. Our findings seek to unlock some of the mysteries of heart regeneration in order to move the possibility of cardiovascular cell therapies forward. We have now found a way to identify the right type of stem cells that create heart cells that successfully engraft when transplanted and generate muscle tissue in the heart, which means we're one step closer to developing cell-based therapies for people living with heart disease."

The ins and outs of muscle stem cell aging

Skeletal muscle has a remarkable capacity to regenerate by virtue of its resident stem cells (satellite cells). This capacity declines with aging, although whether this is due to extrinsic changes in the environment and/or to cell-intrinsic mechanisms associated to aging has been a matter of intense debate. Furthermore, while some groups support that satellite cell aging is reversible by a youthful environment, others support cell-autonomous irreversible changes, even in the presence of youthful factors. Indeed, whereas the parabiosis paradigm has unveiled the environment as responsible for the satellite cell functional decline, satellite cell transplantation studies support cell-intrinsic deficits with aging.

In this review, we try to shed light on the potential causes underlying these discrepancies. We propose that the experimental paradigm used to interrogate intrinsic and extrinsic regulation of stem cell function may be a part of the problem. The assays deployed are not equivalent and may overburden specific cellular regulatory processes and thus probe different aspects of satellite cell properties. Finally, distinct subsets of satellite cells may be under different modes of molecular control and mobilized preferentially in one paradigm than in the other. A better understanding of how satellite cells molecularly adapt during aging and their context-dependent deployment during injury and transplantation will lead to the development of efficacious compensating strategies that maintain stem cell fitness and tissue homeostasis throughout life.

Hypothesis on Skeletal Muscle Aging: Mitochondrial Adenine Nucleotide Translocator Decreases Reactive Oxygen Species Production While Preserving Coupling Efficiency

Mitochondrial membrane potential is the major regulator of mitochondrial functions, including coupling efficiency and production of reactive oxygen species (ROS). Both functions are crucial for cell bioenergetics. We previously presented evidences for a specific modulation of adenine nucleotide translocase (ANT) appearing during aging that results in a decrease in membrane potential - and therefore ROS production - but surprisingly increases coupling efficiency under conditions of low ATP turnover. Careful study of the bioenergetic parameters of isolated mitochondria from skeletal muscles of aged and young rats revealed a remodeling at the level of the phosphorylation system, in the absence of alteration of the inner mitochondrial membrane (uncoupling) or respiratory chain complexes regulation.

For equivalent ATP turnover (cellular ATP demand), coupling efficiency is even higher in aged muscle mitochondria, due to the down-regulation of inner membrane proton leak caused by the decrease in membrane potential. In the framework of the radical theory of aging, these modifications in ANT function may be the result of oxidative damage caused by intra mitochondrial ROS and may appear like a virtuous circle where ROS induce a mechanism that reduces their production, without causing uncoupling, and even leading in improved efficiency. Because of the importance of ROS as therapeutic targets, this new mechanism deserves further studies.

Mitochondrial Quality Control and Muscle Mass Maintenance

Loss of muscle mass and force occurs in many diseases such as disuse/inactivity, diabetes, cancer, renal, and cardiac failure and in aging - sarcopenia. In these catabolic conditions the mitochondrial content, morphology and function are greatly affected. The changes of mitochondrial network influence the production of reactive oxygen species (ROS) that play an important role in muscle function. Moreover, dysfunctional mitochondria trigger catabolic signaling pathways which feed-forward to the nucleus to promote the activation of muscle atrophy. Exercise, on the other hand, improves mitochondrial function by activating mitochondrial biogenesis and mitophagy, possibly playing an important part in the beneficial effects of physical activity in several diseases. Optimized mitochondrial function is strictly maintained by the coordinated activation of different mitochondrial quality control pathways. In this review we outline the current knowledge linking mitochondria-dependent signaling pathways to muscle homeostasis in aging and disease and the resulting implications for the development of novel therapeutic approaches to prevent muscle loss.


With today's news, it certainly seems that senescent cell clearance has come of age as an approach to treating aging and age-related conditions. Some of the leading folk in the cellular senescence research community today published the results from a very encouraging life span study, extending life in mice via a method of removing senescent cells. This is much the same approach employed in one of the first tests of senescent cell clearance, carried out in accelerated aging mice a few years ago, but in this case normal mice were used, leaving no room to doubt the relevance of the results. The researchers have founded a new company, Unity Biotechnology, to develop therapies for the clinic based on this technology. Clearance of senescent cells has been advocated as a part of the SENS vision for the medical control of aging for more than a decade now, and it is very encouraging to see the research and development community at last coming round to this view and making tangible progress.

Senescent cells have removed themselves from the cycle of replication in reaction to cell and tissue damage, or a local tissue environment that seems likely to result in cancer. Their numbers accumulate with age. Most are destroyed by the immune system or their own programmed cell death mechanisms, but enough linger for the long term for their growing presence to be one of the contributing causes of the aging process. These cells behave badly, secreting harmful signals that degrade tissue function, generate inflammation, and alter the behavior of surrounding cells as well. Near every common age-related condition is accelerated and made worse by the presence of large numbers of senescent cells. We would be better off without them, aging would be slowed by the regular removal of these errant cells, and the therapies to make that possible are on the near horizon.

The mouse lifespan study is the important news here, as it demonstrates meaningful extension of median life span through removal of senescent cells, the first such study carried out in normal mice for this SENS-style rejuvenation technology. This sort of very direct and easily understood result has a way of waking up far more of the public than the other very convincing evidence of past years. So it looks like Oisin Biotechnology, seed funded last year by the Methuselah Foundation and SENS Research Foundation to bring a senescent cell clearance therapy to market, now has earnest competition. Insofar as the competitive urge in business and biotechnology speeds progress and produces better results, let the games begin, I say.

Scientists Can Now Radically Expand the Lifespan of Mice - and Humans May Be Next

Researchers have made this decade's biggest breakthrough in understanding the complex world of physical aging. The researchers found that systematically removing a category of living, stagnant cells (ones which can no longer reproduce) extends the lives of otherwise normal mice by 25 percent. Better yet, scouring these cells actually pushed back the process of aging, slowing the onset of various age-related illnesses like cataracts, heart and kidney deterioration, and even tumor formation. "It's not just that we're making these mice live longer; they're actually stay healthier longer too. That's important, because if you were going to equate this to people, well, you don't want to just extend the years of life that people are miserable or hospitalized."

By rewriting a tiny portion of the mouse genetic code, the team developed a genetic line of mice with cells that could, under the right circumstances, produce a powerful protein called caspase when they start secreting p16. Caspase acts essentially as a self-destruct button; when it's manufactured in a cell, that cell rapidly dies. So what exactly are these circumstances where the p16 secreting cells start to create caspase and self-destruct? Well, only in the presence of a specific medicine the scientists could give the mice. With their highly-specific genetic tweak, the scientists had created a drug-initiated killswitch for senescent cells. In today's paper, the team reported what happened when the researchers turned on that killswitch in middle-aged mice, effectively scrubbing clean the mice of senescent cells.

Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16Ink4a-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16Ink4a-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16Ink4a-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.

Unity Biotechnology Launches with a Focus on Preventing and Reversing Diseases of Aging

Unity will initially focus on cellular senescence, a biological mechanism theorized to be a key driver of many age-related diseases, including osteoarthritis, glaucoma and atherosclerosis. "Imagine drugs that could prevent, maybe even cure, arthritis or heart disease or loss of eyesight. It's an incredible aspiration. If we can translate this biology into medicines, our children might grow up in significantly better health as they age. There will be many obstacles to overcome, but our team is committed and inspired to achieve our mission. This has been a long journey, and we're at the point now where we can start making medicines to achieve in humans what we've achieved in mice. I can't wait to see what happens as we move into the clinic."

To close this post, and once again, I think it well worth remembering that SENS rejuvenation biotechnology advocates and supporters have been calling for exactly this approach to treating aging for more than a decade. That call was made based on the evidence arising from many fields of medical research, and from a considered perspective of aging as a process of damage accumulation, one that can be most effectively treated by repair of that damage. The presence of senescent cells is a form of damage. SENS was not so long ago derided and considered out on the fringe for putting forward that position, but for several years now it has been very clear that the SENS viewpoint was right all along. I strongly encourage anyone who remains on the fence about the validity of the SENS proposals for the treatment of aging to reexamine his or her position on the science.


The proteasome is a type of cellular structure tasked with breaking down damaged and unwanted proteins, its activities one part of a broad variety of maintenance mechanisms found inside the living cell. Today I'll point out the latest of a number of studies from recent years to investigate the underlying reasons for associations between declining cellular maintenance and specific aspects of degenerative aging. The researchers noted here have linked proteasomal activity to the vitality of neural stem cells. They show that both decline in aging, but the stem cells can be restored to more youthful vigor when proteasomes are artificially induced to pick up the slack once more.

Stem cells maintain tissues by providing a source of new cells and signals that influence cellular behavior. Even in the brain, stem cell populations deliver a supply of new neurons over time, and this is one of the sources of neural plasticity, the ability of the brain to change, learn, adapt, and (to a limited degree) repair itself. The activity of stem cell populations declines with advancing age, however, most likely a reaction to rising levels of cell and tissue damage. Less activity serves to reduce the risk of death by cancer, but at the cost of a faster decline into frailty and organ failure, the result of failing tissue maintenance. In the brain, this means a progressive loss of neural plasticity, and this is thought to contribute meaningfully to the development of neurodegenerative conditions. It probably has subtle and profound effects on the state of the human mind as well, beyond those caused by obvious structural failures in brain tissue, though that is far harder to prove one way or another.

As is the case for stem cell activity, proteasomal activity is also known to decrease in older tissues. All mechanisms of cellular maintenance go the same way, unfortunately, and this is a recurring theme in aging research. There are many who view aging as at least in part a garbage catastrophe: a downward spiral led by broken mechanisms and a growing inability to keep up. Many models of enhanced longevity have greater maintenance activities than their less fortunate peers. Naked mole rats for example, have very effective proteasomes. Aging is the accumulation of cell and tissue damage, and even repair systems get damaged - though in likelihood these age-related declines are not the direct results of damage, but rather mediated by a complex web of interacting signals and protein levels. For much of the past decade, some researchers have looked towards boosted maintenance, including increased proteasomal activity, as a possible way to slow the onset of aging or treat degenerative conditions. Despite a lot of research and many published papers, little concrete progress towards clinical translation of research has occurred on this front, however.

Essential role of proteasomes in maintaining self-renewal in neural progenitor cells

The breakdown of protein homeostasis has been suggested to be tightly associated with the aging process, because all cells have to keep a dynamic balance between protein synthesis and degradation in order to maintain their integrity and normal functions. In fast-proliferating cells, it is particularly crucial to recycle obsolete macromolecules to provide the raw materials for synthesis of subcellular compartments and molecules to satisfy the requirement of rapid proliferation and/or differentiation. Such a self-renewal ability of cells, however, is gradually compromised and eventually diminished with age. Hallmarks of aged cells include increased accumulation of hyper-oxidative, misfolded, or abnormally-aggregated proteins, all of which result from the dysfunctional cell clearance mechanisms, especially the protein degradation pathway.

The proteasome-dependent degradation is one of such cellular clearance mechanisms for retaining intracellular protein homeostasis, which targets and subsequently degrades damaged, misfolded or redundant proteins. The dysfunction of proteasomes, in turn, may contribute to the occurrence of many aging-related diseases. Various studies have shown that proteasomal activity might be compromised during the aging process in both animals and cells, given that its decrease has been found in a variety of aged tissues in humans, non-human mammals, and even in lower organisms such as fruit flies.

In this study, we investigated the role of proteasomes in self-renewal of neural progenitor cells (NPCs). Through both in vivo and in vitro analyses, we found that the expression of proteasomes was progressively decreased during aging. Likewise, proliferation and self-renewal of NPCs were also impaired in aged mice, suggesting that the down-regulation of proteasomes might be responsible for this senescent phenotype. We previously increased proteasomal activity in bone marrow stem cells by exogenously applying the proteasome activator 18α-GA or genetically over-expressing the β-subunit PSMB5, and found that both methods could effectively improve cell integrity and ameliorate replicative senescence, in addition to enhancements of cell survival and neuronal differentiation following the brain transplantation of PSMB5-overexpressing bone marrow stem cells. In the current study, we observed similar effects of 18α-GA on NPCs.

Lowering proteasomal activity by loss-of-function manipulations mimicked the senescence of NPCs both in vitro and in vivo; conversely, enhancing proteasomal activity restored and improved self-renewal in aged NPCs. These results collectively indicate that proteasomes work as a key regulator in promoting self-renewal of NPCs. This potentially provides a promising therapeutic target for age-dependent neurodegenerative diseases.


After the laboratory, the next stage of development in rejuvenation therapies involves the founding of biotechnology startups. There is no clear-cut point at which research stops being non-profit in the laboratory and starts being for-profit in a venture-funded startup. Every research team eyeballs the time and cost needed to get to the next level, something ready for the first human trial. Once that comes down to a gap that can be crossed with the combination of a seed round and angel investment round - say half a million to a million in funding and a year or two of work with a couple of clearly identifiable goals and go/no-go decisions - then the adventurous will make the leap. As I'm sure you've noticed it looks like a bear market is getting underway, but what better time to pull in investment for a project that might take a couple of years of heads-down work out of the limelight to reach the next stage? Bear markets only last a year or two, so by the time a new biotech startup has completed its first stage work successfully, it'll be ready to catch the headwinds of the next bull market.

Numerous lines of SENS rejuvenation research are, piece by piece, leaving the laboratory for the startup world. This is the success that we as a community have achieved with our years of charitable support for research aimed at advancing the state of the art. Whenever a new SENS-related biotechnology startup launches, bear in mind that a diverse group of people, investors and researchers, have looked at the technology and said "yes, we think can get a prototype therapy for human trials done in a couple of years." It is an important sign of progress, and one that is hard to fake: people with meaningful amounts of money on the line made those calls. You should expect our community to transition in part from one of fellow traveler non-profits and research groups to one made up equally of a network of startups, entrepreneurs, and investors of various stripes, from occasional angels to professionals at venture funds.

Here is a short list of interesting companies I am aware of that are working on SENS-related therapies at various stages, some very new, some years old, and proceeding at differing paces and with different strategies for development. They are not the only companies of interest to people who follow this space: I am omitting Arigos Biomedical, Organovo, and BioViva, among others, but the companies I list below are all very clearly working on aspects of SENS rejuvenation biotechnology. I'm certain there I others that I don't know about at this point - I am certainly far from well connected. I foresee a future in which in addition to the important work still ongoing in the laboratory, we can help to support a incubator-like environment of friendly companies under the SENS umbrella, helping one another succeed, each focused on one slice of the rejuvenation therapies needed to bring an end to aging. Those that succeed will act as guides for the growth of others: in diversity there is the greater chance of finding winning strategies. Importantly, among these companies today there are lot of people who are in this primarily to get the therapies built and out there and available. They are long-term SENS supporters. If they strike it rich, a good portion of that wealth is going to be reinvested in the next cycle of research development because, like us, they have a good idea of which of the two of life and money is more important. That is what success will look like once things become more commercial.


I've posted on the topic of Gensight in the past. This is a French company with tens of millions in venture funding that is built on technology for allotopic expression of mitochondrial genes originally partly funded by the SENS Research Foundation. They are focused on generating a robust commercial implementation for one mitochondrial gene, initially to deploy gene therapies to treat hereditary mitochondrial disease. Creating such a robust implementation is an important foundation for a future effort in which all mitochondrial genes can be backed up to the cell nucleus, and thus the contribution of mitochondrial DNA damage to aging can be eliminated.

Human Rejuvenation Technologies

Human Rejuvenation Technologies is a venture run by philanthropist Jason Hope, who you may recall funded a sizable chunk of the ongoing work on glucosepane cross-link breaking at the SENS Research Foundation back a few years ago. Glucosepane cross-link breaker drug candidates seem to be a few years in the future yet, so Human Rejuvenation Technologies is instead working with a drug candidate for clearing a form of metabolic waste key to plaque formation in atherosclerosis. This candidate is one of the results produced by the long-running SENS Research Foundation LysoSENS program.

Ichor Therapeutics

Ichor Therapeutics has been around for a couple of years, and has done a good job in setting a sustainable lab business on the side. The interesting work here, however, is the continuation of SENS research programs aimed at removing the buildup of A2E, one of the components of lipofuscin that builds up in cells and interferes with cellular garbage disposal. Unusually among the forms of cellular damage, even those involving buildup of metabolic waste such as lipofusin, A2E is linked very directly and solidly to some forms of age-related disease that involve retinal degeneration. In most cases the fundamental damage that causes aging is separated from the end stage of disease by lengthy and barely understood chains of cause and consequence, but here it is very clear that getting rid of A2E is a good thing.

Oisin Biotechnology

Oisin Biotechnology are developing a senescent cell clearance therapy, an approach to treating aging that has definitely arrived with a splash: there are multiple methods demonstrated in mice, and a number of different groups at the point of launching commercial development efforts. Oisin was funded more than a year ago by the Methuselah Foundation and SENS Research Foundation, and you'll be hearing much more about them in the year ahead, I predict.

Pentraxin Therapeutics

Pentraxin Therapeutics is the oldest and slowest of these companies, founded way back in 2001. The SENS-relevant work started in 2008 or 2009 with a partnership with GlaxoSmithKline to develop a treatment to clear transthyretin amyloid, a form of metabolic waste that builds up with age and is linked to cardiovascular disease, osteoarthritis, and death by heart failure in the oldest human beings. A human trial recently produced very positive results, showing significant clearance of amyloid in patients, and this is consequently probably the furthest advanced of all SENS technologies. Unfortunately it is also the most locked up within the slow regulatory system and a Big Pharma partnership. It is hard to say what is going to happen next here, but don't hold your breath expecting to see anything in the clinic soon.

Unity Biotechnology

Unity Biotechnology has emerged from the first successful efforts to clear senescent cells via gene therapy, back in 2011, as well as ongoing programs such as those of the Campisi laboratory. They have a sizable staff for a startup, good venture backing, and are developing treatments based on these methods, but which will be more suitable for use in human patients. You no doubt saw the full court press in the media put on by the various organizational backers of Unity earlier this week. It is great to see such a large number of people pushing the SENS line of damage repair as the approach to treatment of aging. As more companies reach the point of gaining support from deep pockets in the venture community, we will see more of this media attention for SENS-like rejuvenation therapies.


Monday, February 1, 2016

Increased gene expression of FGF21 is associated with calorie restriction and extends life in mice when artificially induced, such as via gene therapy. Researchers here find that the FGF21 response to calorie restriction in humans is quite different, which is a start on the journey to explain exactly how it is that calorie restriction has a much larger effect on mouse life span than on human life span, while the short-term benefits observed to date in both species are very similar:

The adaptive response to starvation includes a series of key physiologic changes in fuel utilization. Certain aspects of the starvation response, such as the depletion of adipose lipid stores and serum triglycerides, could, in theory, provide metabolic benefits if recapitulated outside the context of starvation, such as in obese individuals. This concept underscores the intense excitement elicited by the discovery of FGF21, a novel fasting-induced hormone in murine models. Having been ascribed a central role in coordinating the ketogenic response to starvation, FGF21 also mediates additional metabolically beneficial functions in mice. Although such preclinical mouse data provided a rationale to develop FGF21 or FGF21 mimetics to treat human metabolic disease, the very question of whether FGF21 is a fasting-induced hormone in humans has remained unresolved.

In this study, in which healthy volunteers underwent a prolonged, medically supervised fast, we provide strong evidence for induction of FGF21 over a 10-day period. By documenting the serial dynamics of circulating FGF21, we provide insight into why it has been so challenging to establish FGF21 as a fasting hormone in humans: namely, the protracted time scale necessary to elucidate the response. Not only did it take the full 10 days to demonstrate a statistically meaningful induction of FGF21, but we also observed an initial decline in FGF21 levels in the majority of subjects.

In considering potential explanations for the differing dynamics of circulating FGF21 between mice and humans, it is tempting to invoke the divergent metabolic rates between the 2 species. Indeed, the mass-specific resting metabolic rate of mice exceeds that of humans by a factor of approximately 7, which approximates the time-scale difference in the FGF21 effect between mice and humans. Our data, however, suggest that the difference between mice and humans with respect to FGF21 regulation and function may go beyond the time course of its release into the circulation. In contrast to the pattern observed in fasting mice, the ketogenic response in our human subjects preceded the induction of FGF21. Importantly, in several patients, the onset of ketosis occurred at a time point when serum FGF21 levels had dropped below baseline values. While this study does not exclude the possibility that FGF21 promotes ketone production in some contexts these data argue strongly against a paradigmatic role for FGF21 as a determinant of the human ketogenic response to starvation.

The late increase in FGF21 levels in humans correlated with weight loss and markers of tissue stress, providing a rationale to focus future mechanistic studies on the role of FGF21 in regulating fuel production and trafficking during the latter phase of starvation, with a particular focus on human studies, given the apparent evolutionary divergence in some FGF21 functions between mice and humans. With regard to the potential therapeutic implications of this study, we cannot assume that any hypothesized functional roles of FGF21 in the starved state are relevant to supraphysiologic administration of FGF21 mimetics in patients with metabolic disease.

Monday, February 1, 2016

The popular scientific press here looks at the work of 21st Century Medicine on cryopreservation. Specifically, the topic is the present efforts to provide conclusive proof that low-temperature vitrification of tissue, the process employed at Alcor and other cryonics providers, maintains the fine structures of the brain considered to encode the data of the mind, such as memory. For the many who will die prior to the advent of rejuvenation biotechnologies, this is the only shot at a longer life in the future, and it is to our shame as a society that so few choose this option over oblivion and the grave.

It is interesting to note that many of the people in this field, and their supporters, see the end goal as scanning and transcription of the data encoded in a stored brain into an emulated mind running in software. This is as opposed to restoration and repair of the original tissue via advanced forms of molecular nanotechnology and tissue engineering. The assumption of an emulated copy is very much in evidence in this article. I think this to be a profoundly mistaken strategic goal, as a copy of you is not you.

The soul is the pattern of information that represents you - your thoughts, memories and personality - your self. There is no scientific evidence that something like soul stuff exists beyond the brain's own hardwiring, so I was curious to visit the laboratories of 21st Century Medicine in Fontana, Calif., to see for myself an attempt to preserve a brain's connectome - the comprehensive diagram of all neural synaptic connections. This medical research company specializes in the cryopreservation of human organs and tissues using cryoprotectants (antifreeze). In 2009, for example, the facility's chief research scientist Gregory M. Fahy published a paper documenting how his team successfully transplanted a rewarmed rabbit kidney after it had been cryoprotected and frozen to −135 degrees Celsius through the process of vitrification, "in which the liquids in a living system are converted into the glassy state at low temperatures."

I witnessed the infusion of a rabbit brain through its carotid arteries with a fixative agent called glutaraldehyde, which binds proteins together into a solid gel. The brain was then removed and saturated in ethylene glycol, a cryoprotective agent eliminating ice formation and allowing safe storage at −130 degrees C as a glasslike, inert solid. At that temperature, chemical reactions are so attenuated that it could be stored for millennia. Think of a book in epoxy resin hardened into a solid block of plastic. "You're never going to open the book again, but if you can prove that the epoxy doesn't dissolve the ink the book is written with, you can demonstrate that all the words in the book must still be there ... and you might be able to carefully slice it apart, scan in all the pages, and print/bind a new book with the same words." The rabbit brain circuitry he examined through a 3-D scanning electron microscope "looks well preserved, undamaged, and it is easy to trace the synaptic connections between the neurons."

Tuesday, February 2, 2016

Researchers here use a model to predict aging-associated proteins, those in which damaged and misfolded molecules are noticeable prevalent in aged tissues. Since the model turns up proteins already known to be associated with aging, some of the others in the list may also be worth looking at, and the overall effort can be taken as supporting evidence for some theories on the relative importance of various mechanisms in aging:

Certain proteins known to be associated with aging and age-related diseases such as Alzheimer's disease and cancer are also at a high risk for destabilization caused by oxidation. This finding provides an understanding of how oxidative damage, which is a natural process in aging cells, affects proteins. It could also prove to be a foundation to a better understanding of age-related diseases. When people turn about 80 years of age, approximately half of the body's proteins are damaged by oxidation. Oxidation occurs because of random chemical degradations that are associated with converting food to energy in the presence of oxygen. Oxidation in the human body, mediated by free radicals, damages cellular proteins, lipids, DNA, and other cellular structures that contribute to disease processes.

Researchers used physics principles and computer analysis to evaluate protein electrostatics, or charges. They found that short, highly charged proteins are particularly susceptible to large destabilization and that even a single oxidation event within these proteins is sufficient to unfold its normally balled-up, folded structure. "Our paper explains the molecular mechanism by which natural chemical processes of aging affect our proteins. Our method predicts which proteins are the most at risk of unfolding when they get damaged. We then applied the principle in searching protein databases. Interestingly, we found that the proteins most at-risk for oxidative unfolding included 20 proteins that span a wide-spectrum of functionalities, all of which had been known by researchers previously to be associated with aging." The list of proteins includes telomerase proteins, which play a major role in aging of cells and cancer development by the extending of telomeres; and histones, which are DNA-binding proteins known to be relevant for many processes, including memory loss and cancer. The research could be a first step toward finding other proteins, not currently suspected, that are susceptible to high oxidation, instability and age-related diseases. The proteins could prove to be the key to targeted treatments against certain age-related diseases.

Tuesday, February 2, 2016

Researchers here investigate fruit flies in search of age-related changes in the cellular processes of metabolism that occur in mid-life, early signs of degeneration and damage accumulation. They find that an increase in acetylation that occurs with aging may act to both alter and raise the error rate of protein creation, leading to an increased number of damaged proteins and inappropriate levels of proteins in circulation. In support of this hypothesis, it is noted that more acetylation reduces fly life span, while suppressing the age-related rise in acetylation increases life span:

The aging process is accompanied by characteristic changes in physiology whose overall effect is to decrease the capacity for tissue repair and increase susceptibility to metabolic disease. In particular, the overall level of metabolic activity falls, and errors in the regulation of gene activity become more frequent. Researchers have now shown in the fruitfly Drosophila melanogaster that such age-dependent changes are already detectable in middle age. Genetic investigation of the signal pathways involved in mediating this effect identified a common process - the modification of proteins by the attachment of so-called acetyl groups (CH3COO−) to proteins - that links the age-related changes at the metabolic and genetic levels. Most studies of the aging process employ comparisons between young and old individuals belonging to the same species. "However, in aged animals, many of the potentially relevant physiological operations no longer function optimally, which makes it difficult to probe their interactions. That is why we chose to look in Drosophila to see whether we could find any characteristic metabolic changes or other striking modifications in flies on the threshold of old age and, if so, ask how these processes interact with each other."

Resarchers first made the surprising discovery that middle-aged male flies (7 weeks old) actually consume more oxygen than their younger counterparts. This points to a metabolic readjustment which is accompanied by an increase in mitochondrial activity, and indeed, the researchers noted a rise in the intracellular concentration of acetyl-CoA in these flies. Acetyl-CoA is a metabolite that is produced in the mitochondria, which participates in large number of processes in energy metabolism. Furthermore, it is an important source of acetyl groups for the chemical modification of proteins. "Acetyl groups are attached to specific positions in certain proteins by dedicated enzymes, and can be removed by a separate set of enzymes. These modifications modulate the functions of the proteins to which they are added, and our experiments have shown that many proteins are much more likely to be found in acetylated form in middle-aged flies than in younger individuals."

Strikingly, this is true not only for proteins that are involved in basic metabolism, but also for proteins that are directly responsible for regulating gene expression. "We were able to show that the histones in middle-aged flies are overacetylated. This reduces the packing density of the DNA, and with it the stringency of gene regulation. The overall result is a rise in the level of errors in the expression of the genetic information, because genetic material that should be maintained in a repressed state can now be reactivated. In the prime of their lives, fruitflies begin to produce a surfeit of acetylated proteins, which turns out to be too much of a good thing."

Taken together, these findings indicate that changes in acetylation may be a key factor in the process of natural aging, reflecting alterations in basic metabolism as well as modifying gene regulation. "A rise in the level of protein acetylation seems to be linked to a decrease in life expectancy. For inhibition of an acetylase enzyme which specifically attaches acetyl groups to histones, or attenuation of the rate of synthesis of acetyl-CoA - which reduces the supply of acetyl groups - reverses many of the age-dependent modifications seen in these animals, and both interventions are associated with a longer and more active lifespan." The researchers are now planning to look for comparable effects in mammals. "If that turns out to be the case, then the enzymes that specifically acetylate histones might well be interesting targets for the development of novel therapeutic agents that correct age-dependent dysregulation. Partial inhibitors that reduce enzyme activity without completely blocking it would probably be most effective in this context."

Wednesday, February 3, 2016

This is an interesting short interview with a researcher working on aspects of a stem cell therapy for Parkinson's disease, with unusual results from animal studies in that the transplanted cells survive for a long time. In most first generation stem cell therapies, the cells produce benefits through signaling and do not live long or integrate with patient tissues in any significant numbers. Parkinson's is characterized by the loss of a small but vital population of neurons in the brain, something that happens in the course of normal aging as well, but not to the same degree. Thus for quite some time researchers have been aiming at replacement of these cells as a therapy:

Dr. Xianmin Zeng at The Buck Institute for Research on Aging focuses on potential treatments and therapies for Parkinson's disease. After years of dedicated work creating cell lines and collaborating on a delivery system the Zeng laboratory and their industry collaborators have developed a stem cell based treatment that is ready for human clinical trials. The treatment relies on a specialized process to make and purify nerve cells from induced pluripotent stem cells (iPSCs) which can be implanted into humans. In the process of creating the iPSCs multiple patient lines were also created resulting in an invaluable resource of a wide variety of Parkinson's patient lines. Having this vast variety of patient lines allows researchers to better understand the different mutations that can cause Parkinson's disease.

"Although the best-case scenario is having your own cells modified and implanted back into you, this is a therapy for only one person. An allogeneic donor line after being tested and verified can serve multiple patients. It is a bit like having a blood bank; one line of allogeneic cells will work for many patients, while another line of allogeneic cells will work for a different set of patients. The challenge is to calculate how many different allogeneic lines are needed to work with 90% of the patient population."

Another challenge with Parkinson's disease lies in delivering the desired treatment to the brain. These cells are able to populate the diseased area, differentiating into the appropriate cell type and replacing the dead neurons. One way in which this widespread delivery might be accomplished is to have a single injection that can be multi-pronged, reaching many areas of the brain. If this treatment works it could have a broad impact by serving as as a template to treat a variety of other neurodegenerative diseases. "It is not expected that you would need to do this treatment repeatedly. In the animal studies that we conducted the transplanted cells survived over six months. If one were to extrapolate this to human lifespan then it could be many years in which the cells will both survive and integrate into the brain after treatment."

Wednesday, February 3, 2016

The research community is very interested in loss of neural plasticity in the brain over the course of aging, a slowing of the introduction and integration of new neurons, and diminished pace of change in the connections between nerve cells. If aging is damage, then this is probably the tail end of a complicated chain of reactions to that damage. As seems to be the case for stem cell populations in other tissues, it is plausible that tinkering with signaling in brain tissue might be able to compensate for this loss, overriding some of this evolved reaction to damage without addressing the damage. The open question is the degree to which this approach can be effective; the evidence to date suggests it can produce large enough benefits in comparison to existing medicine to be worth trying, though if the underlying damage remains unrepaired, contributing to all of the other issues that accompany aging, then frailty and death is still inevitable.

As brain cells age they lose the fibers that receive neural impulses, a change that may underlie cognitive decline. Researchers recently found a way to reverse this process in rats. "There's a tendency to think that aging is an inexorable process, that it's something in the genes and there's nothing you can do about it. This paper is saying that may not be true." The researchers studied dendrites - the branch-like fibers that extend from neurons and receive signals from other neurons - in rats. Evidence from other studies in rodents, monkeys, and humans indicates that dendrites dwindle with age and that this process - called dendritic retraction - occurs as early as middle age.

The team wanted to know whether dendritic retraction was already underway in 13-month-old or "middle-aged" rats and, if it was, could they reverse it by giving rats a compound called an ampakine. Ampakines had previously been shown to improve age-related cognitive deficits in rats as well as increase production of a key growth factor, brain-derived neurotrophic factor (BDNF) in the brain. The researchers housed 10-month-old male rats in cages with enriched environments. Eleven rats received an oral dose of the ampakine each day for the next three months while the other 12 rats received a placebo. After three months the researchers examined an area of the rats' brains associated with learning and memory, the hippocampus, and compared that with the hippocampi of two-and-a-half-month-old or "adolescent" rats.

"Middle-aged" rats given the placebo had shorter dendrites and fewer dendritic branches than the younger rats. The brains of rats given the ampakine, however, were mostly indistinguishable from the young rats - dendrites in both were similar in length and in the amount of branching. What's more, the researchers also found that treated rats had significantly more dendritic spines, the small projections on dendrites that receive signals from other neurons, than either the untreated rats or the young rats. The researchers found that anatomical differences between the rats also correlated with differences in a biological measure of learning and memory: the treated rats showed enhanced signaling between neurons - a phenomenon called long-term potentiation. "The treated rats had better memory and developed strategies to explore."

Thursday, February 4, 2016

Cellular senescence is a response to damage or environmental factors such as toxins, wounds, and oxidative stress. It removes cells from the processes of growth and replication, and probably serves, at least initially, as a way to reduce cancer risk. In this paper, researchers remove mitochondria from senescent cells and see measures of their state improve as a result. The publicity materials head in the wrong direction, I think, by talking about aging versus cellular senescence - these are two very different things, and the aging of individual cells has no direct relationship to aging of the organism.

Growth in the number of senescent cells lingering in tissues is a contributing cause of degenerative aging due to their overall bad behavior, but so is mitochondrial damage. This research could be taken as evidence for one way which mitochondrial damage and dysfunction is important in the mechanisms of aging, but it can also be taken as a straightforward improvement in the understanding of how cells manage their transition into senescence. In either case, we already know that both of these processes are targets for near future rejuvenation therapies.

A team of scientists has for the first time shown that mitochondria, the batteries of the cells, are essential for ageing. The researchers found that when mitochondria were eliminated from ageing, senescent cells they became much more similar to younger cells. This experiment was able for the first time to conclusively prove that mitochondria are major triggers of cell ageing. This brings scientists a step closer to developing therapies to counteract cellular senescence, by targeting mitochondria.

As we grow old, cells in our bodies accumulate different types of damage and have increased inflammation, factors which are thought to contribute to the ageing process. The team carried out a series of genetic experiments involving human cells grown in the laboratory and succeeded in eliminating the majority, if not all, the mitochondria from ageing cells. Cells can normally eliminate mitochondria which are faulty by a process called mitophagy. The scientists were able to "trick" the cells into inducing this process in a grand scale, until all the mitochondria within the cells were physically removed. To their surprise, they observed that the senescent cells, after losing their mitochondria, showed characteristics similar to younger cells, that is they became rejuvenated. The levels of inflammatory molecules, oxygen free radicals and expression of genes which are among the markers of cellular ageing dropped to the level that would be expected in younger cells.

The team also deciphered a new mechanism by which mitochondria contribute to ageing. They identified that as cells grow old, mitochondrial biogenesis, the complex process by which mitochondria replicate themselves, is a major driver of cellular ageing. "This is the first time that a study demonstrates that mitochondria are necessary for cellular ageing. Now we are a step closer to devising therapies which target mitochondria to counteract the ageing of cells."

Thursday, February 4, 2016

Researchers have found that iron oxide nanoparticles can act in similar ways to cellular antioxidants such as catalase, soaking up oxidative molecules and reducing oxidative stress and consequent damage. To the degree that this helps mitochondria resist damage, or alters the behavior of mitochondria in a similar way to that of the activity of mitochondrial antioxidants like catalase, this should modestly slow aging. Indeed, that is the result observed here:

In a study on flies, researchers have found that nanoparticles could potentially extend lifespan. The team tested the effects of iron oxide (Fe3O4) nanoparticles on intracellular reactive oxygen species (ROS) levels and their biological consequences on several cell and animal models. Fe3O4 nanoparticles is a type of biocompatible nanomaterial that has previously been widely used for bioimaging, biodiagnostic and therapeutic purposes. Increased ROS production over time has been closely associated with greater risk of metabolic diseases such as type 2 diabetes and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Therefore, there is a need to explore the long-term effects of nanomaterials on intracellular ROS levels, particularly those with promising biomedical applications in vivo.

The researchers found that Fe3O4 nanoparticles could protect cultured cells under various stress conditions, including hydrogen peroxide (H2O2) treatment, through catalase-like activity. They demonstrated that Fe3O4 nanoparticles retained this mimetic activity in vivo, helping to maintain optimal ROS balance, reduce intracellular oxidative stress, suppress cellular damage, delay animal aging and protect against neurodegeneration. These novel effects were further confirmed in Drosophila models of aging, Parkinson's and Alzheimer's disease. The researchers hope that this study opens up new opportunities for the therapeutic use of Fe3O4 nanoparticles in the treatment of metabolic disorders, neurodegenerative diseases and aging.

Friday, February 5, 2016

There is a fairly strong connection between the small cryonics industry, focused on preserving the human mind following death in order to offer a chance at renewed life in a more technologically capable future, and present efforts to reversibly cryopreserve organs. The technologies used are much the same, and there is a fair degree of overlap in the people involved and the sources of funding. To my eyes success in organ cryopreservation, and consequent growth of an industry focused on making the logistics of transplantation and near future creation of new organs much easier, is the most plausible path to greater public acceptance of cryonics. When livers and hearts can be reliably vitrified, stored for years, and restored as needed, then it isn't a leap to understand that, with further progress and suitable techniques, this could be done for the brain as well.

Over the course of an average winter North American wood frogs, Rana sylvatica, may freeze solid several times. They are able to get away with this by replacing most of the water in their bodies with glucose mobilised from stores in their livers. That stops ice forming in their tissues as temperatures drop. When things warm up again, the frogsicles thaw out, with no evident ill effects. What frogs do without thinking, human researchers are trying, with a great deal of thinking, to replicate. The prize is not the freezing and reanimation of entire people but the long-term preservation of organs for transplant.

According to the World Health Organisation, less than 10% of humanity's need for transplantable organs is being met. The supply has fallen as cars have become safer and intensive-care procedures more effective, and part of what supply there is is lost for want of an instantly available recipient. Cooled, but not frozen, a donated kidney might last 12 hours. A donated heart cannot manage even that span. If organs could be frozen and then thawed without damage, all this would change. Proper organ banks could be established. No organs would be wasted. And transplants that matched a patient's requirements precisely could be picked off the shelf as needed. The problem is that water expands when it freezes. If that water is in living tissue, it does all sorts of damage in the process. But an alliance of experts, ranging from surgeons and biochemists to mechanical engineers and food scientists, is attempting to overcome this inconvenient fact. And, after years of labour, many of them think they are on the threshold of success, and that cryopreservation will soon become a valuable technology.

There are in fact many cryopreservationist ideas around - so many that some think a little co-ordination is in order. That is the purpose behind the Organ Preservation Alliance (OPA), an American charity. Last year it persuaded America's defence department, an organisation with an obvious interest in transplants, to seed seven cryopreservation-research teams with money. The XPRIZE Foundation is considering offering an award to any team that can transplant into five animals organs that have been cryopreserved for a week. The research-funding arm of the Thiel Foundation has given a grant to Arigos Biomedical, a firm working on high-pressure vitrification. New firms abound: Tissue Testing Technologies is working on ways of warming organs uniformly; Sylvatica Biotech is perfecting recipes for cryoprotectants; X-therma is attempting to mimic cryoprotective proteins. The cryopreservation race is on, then. And the winning post is the organ bank.

Friday, February 5, 2016

Researchers here find an association in an older study population between the presence of cytomegalovirus (CMV) - and other common herpesviruses - and the observed degree of cognitive decline. A good deal of evidence from past years supports the theory that CMV accelerates immune system aging, causing the immune system to devote ever more of its limited capacity to uselessly fighting CMV rather than productively carrying out its other tasks. Our immune response is incapable of clearing CMV from the body, and the virus lingers to return in force again and again regardless of the effort devoted to battle it. Since immune failure is a large component of age-related frailty, this is an important topic, and more consideration should be given to approaches that might fix the problem, such as selective destruction of CMV-focused immune cells to free up space for replacement with useful immune cells. As a further consideration, since portions of the immune system serve specialized support roles in brain tissue, it isn't a stretch to think that immune dysfunction may be a contributing cause of cognitive decline in aging.

Certain chronic viral infections could contribute to subtle cognitive deterioration in apparently healthy older adults. Many cross-sectional studies, which capture information from a single time point, have suggested a link between exposure to cytomegalovirus (CMV) and herpes simplex viruses (HSV) 1 and 2, as well as the protozoa Toxoplasma gondii and decreased cognitive functioning. "Our study is one of the few to assess viral exposure and cognitive functioning measures over a period of time in a group of older adults. It's possible that these viruses, which can linger in the body long after acute infection, are triggering some neurotoxic effects."

The researchers looked for signs of viral exposures in blood samples that were collected during the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study, in which more than 1,000 participants 65 years and older were evaluated annually for five years to investigate cognitive change over time. They found CMV, HSV-2 or toxoplasma exposure is associated with different aspects of cognitive decline in older people that could help explain what is often considered to be age-related decline. "This is important from a public health perspective, as these infections are very common and several options for prevention and treatment are available. As we learn more about the role that infectious agents play in the brain, we might develop new prevention strategies for cognitive impairment." Now, the researchers are trying to determine if there are subgroups of people whose brains are more vulnerable to the effects of chronic viral infection.


Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.