Fight Aging! Newsletter, May 2nd 2016

May 2nd 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.

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  • The Scientist on BioViva's Initial Test of Human Gene Therapies
  • It Looks Like UNITY Biotechnology is Taking the Drug Development Path to Senescent Cell Clearance
  • Opponents of Longevity Science Should be Encouraged to Think Critically About How Exactly They Want to Die
  • A Brace of Articles on Cryonics
  • A Most Interesting Data Set Covering the Longevity of Polish Elite Athletes Across Much of the 20th Century
  • Latest Headlines from Fight Aging!
    • The Revolution Against Aging and Death (RAAD) Festival
    • IL-33 Clears Amyloid and Reverses Symptoms in a Mouse Model of Alzheimer's Disease
    • Evidence for Cross-Linking to Impair Muscle Stem Cells
    • If Nothing is Done, Sarcopenia Incidence Will Increase Greatly
    • Another Example of Cryonics in the Popular Press
    • Chronic Inflammation Harms Hematopoietic Stem Cells
    • The Latest Results from a Trial of Chimeric Antigen Receptor Immunotherapy to Treat Cancer
    • Thermoregulation in Aging and Alzheimer's Disease
    • A Recent Study of Nicotinamide Riboside Supplementation
    • SERCA2a Gene Therapy to Treat Pulmonary Hypertension


The Scientist has published a measured piece on the first results from BioViva's initial test of human gene therapy, telomerase and follistatin overexpression, and the broader context in which this single person test took place. The results indicate that the telomerase gene therapy most likely worked in the sense of delivering telomerase to a significant number of cells, including the immune cells used to measure average telomere length. That is an important thing to validate up front, before thinking about any sort of other outcomes, or expanding to a trial of some sort. Historically, gene therapies have proven to be highly varied in their effectiveness when it comes to uptake in target cells: in animal studies, the result might be 5% uptake, or it might be 60% uptake, or anywhere in between. A lot of work has gone into trying to make things more reliable over the past decade, but for many years yet there will be questions as to whether any particular formulation works well enough to build upon. That said, the error bars are large in these measurements, and further data is definitely called for.

First Data from Anti-Aging Gene Therapy

Last year, Elizabeth Parrish, the CEO of Seattle-based biotech firm BioViva, hopped a plane to Colombia, where she received multiple injections of two experimental gene therapies her company had developed. One is intended to lengthen the caps of her chromosomes (called telomeres) while the other aims to increase muscle mass. The idea is that together these treatments would "compress mortality," by staving off the diseases of aging - enabling people to live healthier, longer. Last week, BioViva reported the first results of Parrish's treatment: the telomeres of her leukocytes grew longer, from 6.71 kb in September 2015 to 7.33 kb in March 2016. The question now is: What does that mean? The company announced Parrish's response as success against human aging, having "reversed 20 years of normal telomere shortening." Over the phone, Parrish was more measured in discussing the implications of the finding, which has not yet undergone peer review. "The best-case scenario would be that we added 20 years of health onto the leukocytes, and the immune system might be more productive and catch more of the bad guys. But we have to wait and find out. The proof will be in the data."

Much more data are needed before claiming success against aging, said Dana Glei, a senior research investigator at Georgetown University. "We haven't established a causal link between telomere length and health. If it's like gray hair, dying your hair won't make you live longer." An n of one won't give us the answer, but Parrish's personal trial is the start of what BioViva hopes to accomplish: the first clinical studies using a gene therapy to stall aging and increase health span. The company's approach is backed by preclinical evidence - in particular, that from María Blasco's group at the Spanish National Cancer Research Centre (CNIO). In 2012, Blasco's team reported the results of a telomerase gene therapy in mice. The enzyme telomerase, encoded by the TERT gene, lengthens telomeres. "We demonstrated that AAV9-Tert gene therapy was sufficient to delay age-related pathologies and extend both median and maximum longevity in mice," said Blasco, who is not involved with BioViva. "Many pathologies were delayed, including cancer."

There is another potential weakness of the BioViva data: measurement error. The 9 percent difference between Parrish's before and after telomere lengths is within the measurement error of most laboratories. Houston-based SpectraCell Laboratories conducted the telomere length assay for BioViva. Jonathan Stein, the director of science and quality at SpectraCell, said that most telomere-length assays have a variance of 8 percent, and his firm's test is in line with that number.

The other gene therapy Parrish received - the gene encoding the follistatin protein - is supported by human data, at least in the context of people with muscle disorders. (There are not yet data demonstrating the effects of follistatin gene therapy on aging-related muscle loss.) Follistatin inhibits myostatin, which puts the breaks on muscle growth and therefore makes it an attractive therapy for muscular dystrophies. Early clinical trials on six people with Becker muscular dystrophy, for instance, showed that four of them could walk longer distances after the follistatin gene therapy. Parrish said she expects MRI data on her muscles' response to the treatment in about a month. Working with regulatory agencies has been a sticking point for BioViva, hence Parrish's trip to Colombia. Her controversial move - to skirt oversight by the US Food and Drug Administration by receiving the gene therapies outside the country - prompted a member of the company's advisory board, the University of Washington's George Martin, to resign. Parrish said she is now traveling the globe to find a regulatory partner willing to approve human clinical trials. "When I started looking into this, it seemed like a crazy science," she said. "But it's a crazy science whose time has come."

If you read around online discussions of BioViva's work, you'll find opinions to be fairly polarized. It is clearly the case that a fair number of people in the sciences really, really don't like it when anyone departs from the standard regulatory script of spending a lot of money and time keeping various government agencies happy, and set off to do something adventurous and entirely legal in another jurisdiction that regulators disallow in their own. This might be something like crabs in a bucket, perhaps, but the scientific community has always fiercely attacked those who deviate from the orthodoxy. Maintaining the scientific method in the face of those who are in fact out to undercut its foundations is a constant battle, and this is understandable. Yet the present system of regulation is not the embodiment of the scientific method, and certainly not the only way to conduct technological development resulting from science. Someone has to be the first human subject after animal studies have proven promising, and medicine has a long and noble history of self-experimentation to prove safety and capability, or even for the purposes of discovery. Many of the people who did this, and in some cases suffered for it, and as a result succeeded in producing new and useful medicine are regarded as brave pioneers. Rightfully so, I think.

What do regulators add to this picture other than barriers and objections? It doesn't require a regulator to design and carry out ethical studies in human medicine, and the present state of medical regulation is so ridiculously overblown, costly, and constrained that if everyone went by the FDA book, it would be a decade or more before anyone could legally access gene therapies intended to compensate for aspects of aging. Even that would only happen after the expenditure of billions, ensuring that only very large entities could control and deliver this sort of therapy: Big Pharma and government work hand in hand to the tune of their perverse incentives, limiting rather than expanding opportunities for progress. If you want a dynamic market of many small competing groups, innovative and rapid, then the heavy hand of regulation has to go. At present the only realistic way to go about this is to embrace the medical tourism marketplace and transparency in development: fund small trials, make all the data public, license the technology widely, and let educated patients decide on their options.

Freedom to choose and differences of opinion on the utility of specific therapies are important. For my money, I'm happy to let someone else go first in the case of telomerase gene therapy, which seems riskier than myostatin or follistatin gene therapies given the current state of evidence. I would be made more comfortable by trials in something other than mice, a species that is quite different from us in terms of its telomere dynamics and thus cancer risk profile following this sort of treatment. While telomerase gene therapy actually reduces cancer risk in mice in some cases, perhaps by spurring greater immune activity, along with extending life and reducing incidence of disease, there is no guarantee that the various changes involved will balance in the same way in humans. The falling cost and increasing reliability of gene therapy these days means that there are enough interested people for this to move straight to human testing, however - which isn't unusual in many areas of medicine, I should add.

Even if the economics were different, it is clear that telomerase gene therapies would still be heading for human trials one way or another. There are research groups with enough data in mice and the interest to move forward: telomerase therapies appear to be in essence another way to spur greater activity in old stem cells, and thus improve health and extend life, and all such approaches are gathering attention these days. The established research groups may well continue to work within the regulatory gauntlet while those less impeded forge ahead much more rapidly. This will be a repeat of the development of the stem cell industry over the past two decades, parallel lines inside and outside the gilded cage of regulatory capture. It was just about a decade between the availability of stem cell therapies via medical tourism and the capitulation of the FDA allowing the first classes of treatment in the US, and it certainly would have been longer without the pressure of having these treatments available so widely elsewhere in the world.


UNITY Biotechnology and Oisin Biotechnologies are both early stage startups working on commercial development of therapies capable of clearance of senescent cells. Since accumulation of senescent cells is one of the root causes of aging and age-related disease, periodic removal of these cells is a narrowly focused form of rejuvenation. There are a number of other forms of damage and disarray that contribute to degenerative aging, and all will have to be fixed if aging is to be controlled by medicine, but an individual with fewer senescent cells is absolutely better off than one with more senescent cells regardless of the state of other forms of damage. Earlier this year researchers associated with UNITY Biotechnology published the results of the first life span study in normal mice engineered to destroy their own senescent cells, showing a 25% extension of median life span.

While the Oisin Biotechnologies principals have been pretty open on the topic of how their approach to senescent cell clearance works - it is a form of sophisticated gene therapy - the path chosen by UNITY Biotechnology remains less clear. In part this is because the public research based on gene therapy in mice that led to the life span study noted above is not something that could easily be adapted for use in human trials: it could be done, but almost every other option on the table would be both substantially easier to accomplish and more palatable to regulators. There is a trail of patents for other research leading in to the merger of groups that formed the company, but they cover a fairly wide selection of possible methodologies, including the use of immunotherapies and engineered viruses.

Gene therapies, immunotherapies, and more esoteric modern medical technologies are not the only possible approach to senescent cell clearance, however. In the past couple of years research groups have produced classes of drug - now called senolytic compounds - that can selectively drive senescent cells to self-destruct via the process of apoptosis. The combination of dasatinib and quercetin, for example, removes enough senescent cells in enough different tissues to produce meaningful benefits in mice. It isn't unreasonable to think that this type of result can be improved upon to the point at which it is a competitive option. Judging from recent news, it seems that UNITY Biotechnology will take the apoptosis-inducing drug development path, and, interestingly, is also setting up from the outset to deploy therapies outside the US in less heavily regulated regions:

Ascentage Pharma and UNITY Biotechnology Announce Collaboration for the Development of Senolytic Healthspan Therapies

China-based Ascentage - which is currently working on apoptosis-targeted cancer treatments - will work with UNITY Biotechnology to develop senolytic treatments for age-related diseases in an attempt to roll the back years for seniors. UNITY said it has also demonstrated in animal models that clearing senescent cells reverses or prevents many age-related pathologies, including: osteoarthritis, atherosclerosis, glaucoma, and kidney disease. "At UNITY, we have demonstrated that senescence is a key mechanism in aging and age-related disease. We have evaluated a wide panel of drug candidates that clear senescent cells, and Ascentage's compounds are some of the best we've seen. Access to their compound library through this collaboration will significantly accelerate our efforts to develop drugs to improve healthspan by halting or reversing several age-related diseases."

The biotech chose Ascentage as its partner in this anti-aging field "not only because of its cutting-edge technology, but also because this partnership will allow us to reach a global market." As part of the deal, the companies will also form a joint venture for the development and commercialization of senolytic drugs in China. Though specific terms are undisclosed, Ascentage has said it will acquire an equity interest in UNITY, and in return, the company will make an investment in Ascentage. Robert Nelsen, the co-founder and managing director of ARCH Venture Partners and a UNITY board member, will join the Ascentage board as an observer.

Ascentage Chairman and CEO Dr. Dajun Yang added, "We are one of the leading biopharmaceutical companies with clinical stage compounds targeting key proteins that control programmed cell death pathways. We will continue our efforts to advance clinical stage compounds for targeted anti-cancer therapy and are very pleased to work with UNITY for several unmet medical indications outside of the oncology space, with each aging-related disease potentially representing a multi-billion market."


If you survey people on the topic of developing new medical technologies to enable longer lives, you'll find what looks like widespread opposition to the idea. We are a very conformist species, and in an environment in which everyone else ages to death by 80 or 90, that life span is the goal that many people declare themselves set for - but with a few years added on top to signal personal superiority without veering into a claim that would cause loss of status for other reasons. There is little to no thought given to the realities of the situation, the suffering and pain and loss; this is plain vanilla conformism. Similarly, we live in an age in which anti-technology, pro-death environmentalist philosophy has become so mainstream that the average person in the street feels the need to declare themselves in favor of fewer people, shorter lives, less growth, and less technological progress in order to conform. The Malthusian delusion of impending or actual overpopulation is used as a justification to do nothing to prevent the deaths of billions, and at the small scale as another reason not to publicly declare the urge to live longer than your parents.

People who don the hair shirt to decry their wealth, the technology that sustains them, and their life spans, as well as attempts to improve these metrics, are invariably far from poor when their position in life is considered in the context of the bigger picture. There is a level of attainment in society as a whole at which people become sufficiently insulated from the realities of poverty, or the realities of a lack of technology, or the realities of old age, to forget how things used to be or how life is lived by those who are actually poor or frail. This is pervasive in wealthier nations. Too many people fail to critically consider what it would actually mean to be aged, to have your friends dying around you, and to be diminished, weak, in pain, and dependent. They don't give serious thought as to how exactly it is they will die in this model for the future they put forward, in which their span of health and years follows that of their parents. Then there are the hypocrites, those who have given it thought, but take the shallow path of conformity, helping to weave the web of quiet lies, distortions, and omissions that pervade so much of our society.

The point is made here that perhaps we advocates should do more to persuade people to think meaningfully about what exactly it is that they plan for their own fate. There are personal consequences that accompany the goals declared in opposition to progress in medicine to treat aging, or even when simply following the herd to say that you don't want to live any longer than your parents or grandparents. Many people have a profound misunderstanding of the relationship between medicine, aging, and age-related disease, and of what that will mean for their own lives. Yet they are all doing their part to make it incrementally more difficult for improvements in medicine to be funded, to gain support, and to come into being. On the large scale and over the long-term, the progress that happens is the progress that has broad support across the population as a whole.

How will you die? Cancer, Alzheimer's, Stroke?

I have stated that it is basically a matter of time before we get the diseases of old age (cancer, stroke, dementia...) under control. It is impossible to tell when it will happen. Could be a couple of decades, could be 45 years, could be a century or a bit more. As a precaution, you should never trust anyone who says he can predict the future more than a couple of years in advance. However, progress that is not impossible in principle tends to reliably happen, on its own schedule. Whenever we will get the diseases of aging under control, we will end up with drastically extended healthspan. Simply put, most of us end up sick or dead because of the diseases of old age. Without these diseases, we would end up healthy for much longer. Stating that the diseases of aging will come under control at some point in our future should not be controversial. And you would hope that people would see this as a positive outcome.

Not so.

The prospect that we may finally defeat aging is either rejected as being too improbable, or, more commonly, is rejected as being undesirable. Recently, one of my readers had this very typical reaction: "As for extending human life, I'm not for it." If you tend to agree with my reader, please think it through. Aging does not, by itself, kills us. What kills us are the diseases that it brings, such a stroke, dementia, cancer. So if you are opposed to people living healthier, longer lives, then you are favorable to some of these diseases. I, for one, would rather that we get rid of stroke, cancers and dementia. I do not want to see these diseases in my family.

If you are in favor of short human lifespans through aging, then you must be opposed to medical research on the diseases of aging such as dementia, stroke, and cancer. You should, in fact, oppose anything but palliative care since curing dementia or cancer is akin to extending lifespan. You should also welcome news that members of your family suffer from cancer, Parkinson's and Alzheimer's. They will soon leave their place and stop selfishly using our resources. Their diseases should be cause for celebration. Of course, few people celebrate when they learn that they suffer from Alzheimer's. Yet this disease is all too natural. Death is natural. So are infectious diseases. We could reject antibiotics because dying of an infection is "natural". Of course, we do not.

I am sure that, initially, some people expressed concerns regarding the use of antibiotics. Now that we are starting to think about eliminating the diseases of aging, people object to that as well. But let me assure you that when it comes down to it, if there are cures against the diseases of aging, and you are old and sick, you will almost certainly accept the cure no matter what you are saying now. And the world will be better for it. Please, let us just say no to dementia, stroke and cancer. They are monsters.


I can only speculate as to why a set of better than usual articles on the non-profit cryonics industry have appeared in various popular press publications recently. I pointed out one of them yesterday, and here I'll offer links to another two. While attention from the press tends to come and go in cycles, the past decade, and especially the last few years, has seen a considerable improvement in the quality and tenor of coverage: popular science articles on cryonics providers and human interest pieces on the community of supporters and advocates. This is probably due to a number of factors, among which are the slow burn of low-key publicity efforts on the part of the longer-standing providers such as Alcor and the Cryonics Institute, and the layering of credibility in the journalism community that comes with repeated exposure. I would say, however, that the most important contribution comes from progress in the sciences, firstly the accumulation of better evidence to demonstrate preservation of the fine neural structure thought to encode the data of the mind, and secondly from growing interest in the use of reversible vitrification to improve the industry of tissue engineering and organ transplantation.

Cryonics as an industry offers indefinite low-temperature storage of at least your brain immediately following clinical death. For so long as the data of the mind is preserved, the possibility exists for restoration in a future with more capable technology. Some form of fairly mature molecular nanotechnology and near complete control of cellular biochemistry will be needed, and at the present pace of progress it might take a lifetime to get from here to the point at which revival is a realistic but very expensive process, and another few decades to make it cheap enough that revival is likely. The odds of success for this venture are unknown, depending on many factors that are entirely out of of the control of any one individual, but the odds offered by all of the other presently available end of life choices are zero. Like every effort to extend healthy life, it is all about moving the odds in the right direction, not about certainties.

Vitrification in low-temperature storage, the preservation method presently used by cryonics providers, is attained through the use of cryoprotectant compounds. Cryoprotectants are infused into tissues during cooling, and the ice crystal formation that characterizes straight freezing is minimized in the glass-like vitrified result. The difference is enormous. At this point, researchers have shown that vitrified and restored nematode worms appear to retain memory, and have produced forms of vitrification that result in excellent preservation of fine structure. Reversible vitrification has been carried out in a rabbit kidney, with following transplantation and function for a period of time. A number of research groups are investigating reversible vitrification as a way to greatly improve the logistics of tissue engineered or donated organs: if an organ can be stored indefinitely, then many of the costs and complications associated with these fields vanish. Given all of this, it becomes harder for journalists to reject the cryonics industry out of hand. That doesn't stop them engaging in the traditional practice of finding ridiculous and speculative objections in other places, of course:

If cryonics suddenly worked, we'd need to face the fallout

Right now, in three facilities in the US and Russia, there are around 300 people teetering on the cusp of oblivion. They exist in a state of deep cooling called cryopreservation, and entered their chilly slumber after their hearts had stopped beating. Before undergoing true cell death, the tissues of their brains were suspended using an ice-free process called vitrification. All are legally deceased, but if they could they speak, they would likely argue that their remains do not constitute dead bodies at all. Instead, in a sense, they are just unconscious. No-one knows if it's possible to revive these people, but more and more of the living seem to believe that uncertainty is better than the alternative. Around 1,250 people who are still legally alive are on cryonics waiting lists, and new facilities are opening in Oregon, Australia and Europe soon. "We have a saying in cryonics: being frozen is the second worst thing that can happen to you. There's no guarantee you'll be able to be brought back, but there is a guarantee that if you get buried or cremated, you'll never find out."

To the uninitiated, cryonics might seem the stuff of are slowly chipping away at the possibility of revival. Most recently, a team succeeded at thawing a previously vitrified rabbit brain. Even after several weeks of storage, the synapses that are thought to be crucial for brain function were intact. While a thawed out rabbit brain does not a fully revitalised person make, some believe that cryogenic revival might someday be as commonplace as treating a case of the flu or mending a broken arm. "This is really not so earth-shattering or philosophically weird as you might think. It's just medicine - another form of healthcare that helps people who are seriously sick. Once you get your head around that, it's much less scary."

But assuming cryonics does wind up working, for the newly reborn citizens of the past there would be more to their stories than simply opening their eyes and declaring a happy ending. Instead, they would immediately face the challenge of rebuilding their lives as strangers in a strange land. But even if a cryogenically preserved person was on his or her own, that would necessarily be a deal breaker for eventually attaining happiness. "If you were on an airplane today with all your family and friends and it crashed and you're the only survivor, would you commit suicide? Or would you go out and put your life back together, and make new family and friends? Besides, it doesn't make sense that they'd take the time to revive people into some dystopian, backward future. You can't have the technology to wake people up and not have the technology to do a bunch of other great things, like provide abundance to the population."

What Exactly Is Life After Death if You're a Cryonicist?

While there's plenty to debate about life after death, what about life after a deep-freeze at minus 196 Celsius? For many people in the cryonics community, this is a very serious and expensive question, one that begins with the definition of death itself. The preservation process begins as soon as possible after "legal death" - the point when a person can no longer be resuscitated by current technology - is announced, and a person can pick to have only his or her brain frozen or the entire body. Many cryonicists, according to the Alcor Life Extension Foundation, believe that a person's memory, identity, and personality remain stored inside the brain even after a human being is legally declared dead. They equate the brain to a hard drive in a computer - simply because you turn off a computer doesn't mean the hard drive is wiped out. They hope in the future the medical community can figure out a way to turn back on whatever caused the body to die so that the mind can once again live.

For a decade, Murray Ballard spent time in the United States, the United Kingdom, and around Europe and Russia meeting with individuals and institutions in the cryonics community. Ballard said he initially became hung up on the technical aspects of cryonics and photographed it accordingly, but the more people he met, the more he realized the story was really about the individuals who are part of the community and their interest in perhaps one day being brought back to life. Most of the people he met thought of cryonics as an adventure. He said they tend to shy away from the word faith, possibly because of religious undertones, and they're aware that the odds of this working are quite slim. However, they say, it still beats the alternative. "You can't argue with the fact that you're better off being cryogenically preserved than buried or cremated. In that case you'll never be brought back to life. It's a stopgap, a way of just doing the best that we can at the moment. They can't wait for cryonics to be an outdated thing."


Today I noticed an open access paper in which the authors examine mortality data for Polish Olympic athletes over the past 90 years or so, and compare it with established historical data for the general population. This blends two topics that are occasionally covered here at Fight Aging!: firstly, the growth in human life expectancy in recent history and its causes, and secondly the topic of how regular exercise and life expectancy interact. It is the present consensus that elite athletes, those at the top of their profession, live longer than the rest of us, but it remains open to debate as to whether this is because more exercise is better, or because very robust people who would have lived longer anyway are more likely to enter the world of professional athletics. Researchers want to map the dose-response curve for exercise, in other words. Even though there is very good, very solid evidence for the benefits of regular moderate exercise versus being sedentary, going beyond that to a more nuanced view of what more or less exercise does for health is a challenging goal given the starting point of statistical snapshots of data from various study populations.

Studying the history of life expectancy isn't much easier, though there the challenges tend to revolve around the ever-decreasing quality of data as you look further back in time. The 20th century marked transitions from hopeful aspiration to solid accomplishment in all fields of medicine, too many profound advances in the capabilities of medical science and practice to list here. As the decades passed, this important progress focused ever more on treatments for age-related conditions. An individual born in the US in 1900 suffered through the end of the era of poor control of infectious disease, prior to modern antibiotics and antiviral drugs, and likely benefited little from later progress towards better control of heart disease and other common age-related diseases. An individual born in the US in 1950, on the other hand, enjoyed a youth with comparatively little fear of disease, and is probably still alive today, with access to far more capable therapies than existed even a couple of decades ago.

Given all of this, one of the interesting things to note in the analysis of the Polish data is that the elite athletes born in the early 20th century appear to have a lower rate of aging than the general population, as determined by a slower rise in mortality over time, but that this difference between athletes and the average individual is greatly diminished for people born in the latter half of the 20th century. This suggests, roughly, that advances in medicine from 1900 to 1950 had a leveling effect, bringing up the average, preventing early deaths, but doing little to address age-related disease. That said, there is a large variation in results across the range of similar studies, both those that look at the history of longevity, and those that look at populations of athletes at a given time. It is wise to consider epidemiological studies in groups rather than one by one, and look for common themes. Still, this one is a fascinating data set for the way in which it combines historical trends and exercise in the study of aging.

Examining mortality risk and rate of ageing among Polish Olympic athletes: a survival follow-up from 1924 to 2012

A sedentary lifestyle is associated with the onset of chronic diseases including ischaemic heart disease, type-II diabetes and neurodegenerative diseases. Frequent exercise is perceived as a major behavioural determinant for improved life expectancy and a slower rate of ageing. There is little doubt that frequent exercise is beneficial for individuals' well-being, and an active lifestyle reduces the risk for chronic diseases. However, it is still uncertain whether the rate of ageing decelerates in response to frequent and intense physical exercise. Our attempt is the first empirical study to show the application of a parametric frailty survival model to gain insights into the rate of ageing and mortality risk for Olympic athletes.

Our participants for this parametric frailty survival analysis were Polish athletes who had participated in the Olympic Games from 1924 to 2010. We assumed that these athletes were elite in their preferred sports expertise, and that they were engaged in frequent, if not intense, physical exercise. The earliest recorded year of birth was 1875, and the latest was in 1982; total N=2305; male=1828, female=477. For reliable estimates, mortality improvements by calendar events and birth cohort had to be taken into consideration to account for the advancements made in medicine and technology. After the consideration of mortality improvements and the statistical power for parametric survival analysis, we restricted our analysis to male athletes born from 1890 to 1959 (M=1273). For reliable estimates, we preassigned recruited athletes into two categorical cohorts: 1890-1919 (Cohort I); 1920-1959 (Cohort II).

Our findings suggest that Polish elite athletes in Cohort I born from 1890-1919 experienced a slower rate of ageing, and had a lower risk for mortality and a longer life-expectancy than the general population from the same birth cohort. It is very unlikely that these survival benefits were gained within a short observational time. Therefore, we argue that participation in frequent sports from young adulthood reduces mortality risk, increases life-expectancy and slows the rate of ageing. The age-specific mortality trajectories of Cohort I elite athletes also suggest frequent exercise can decelerate the rate of ageing by 1% with an achievement of threefold risk reduction in mortality. In comparison with those of the general population, the differences in energy expenditure, behavioural habits, body mass and sports expertise were likely to be the contributing factors to the higher variance in lifespan among elite athletes.

In Cohort II, the estimated rate of ageing is highly similar between elite athletes and the general population, which contradicts our estimates for Cohort I. This may be attributed to mortality improvements from year 1920 onwards in Poland. These mortality improvements have changed individuals' susceptibilities for different causes of death, which has resulted in an increased variation in lifespan both in the general population and for elite athletes. Interestingly, the comparison of the rate of ageing of elite athletes in Cohort I and II shows a similar rate of ageing. Among the elite athletes, the estimates suggest that Cohort II individuals benefited from a 50% mortality risk reduction as compared with individuals born in Cohort I. The estimated overall mortality risk of the Polish general population is 29% lower in Cohort II than in I.



The Revolution Against Aging and Death (RAAD) Festival will be held in California this coming August. The list of speakers is a fascinating combination of the old and the new in the life extension advocacy community: people who have spent decades focused on supplements, health optimization, and the like on the one hand, representatives of the new field of rejuvenation biotechnology on the other, topped off by futurists and advocates whose efforts span these eras.

It is undeniably true that the "anti-aging" industry, for all that it is wall to wall fraud and lies, has built an enormous delivery network and megaphone, and that a lot of the people involved are genuinely passionate about the end goal of radical life extension and the end of aging. It is one of the many paradoxes of the broader community that despite this passion they spend their efforts on businesses and products that cannot make any real difference, and are probably doing more harm than good when you consider how their marketing affects public perception of legitimate work on extending healthy human lives. Nonetheless, there is an argument for engaging the more legitimate end of this industry in order to prepare the ground for a near future of actual, working treatments for aging, and increase the chances for a rapid transition of the first rejuvenation therapies into clinics worldwide. RAAD Festival is an example of that mindset in action, coupled with a determination to shift public discussions of longevity science and the bounds of the possible towards the goal of indefinite healthy life spans:

Join us for the largest ever gathering of radical life extension enthusiasts to learn the latest scientific advancements, connect with like minded people, gain vital insights to extend your health and wellbeing, become a more empowered and effective advocate, interact with leaders of radical life extension, and have a blast celebrating our unlimited future together with music and performances. This is our time to shine. It's time for us to come together, to learn about the newest life extending science and super longevity strategies, to take pride in our progressive views, and to be empowered to make our voices heard. RAAD Fest combines the energy and fun of a festival, the empowerment and interaction of personal development, with cutting edge science presented for a lay audience to create the first and best holistic radical life extension event ever. Hear from top scientists, entrepreneurs and thought-leaders addressing every aspect of radical life extension, from nutrition and new gene therapies, to the power of personal intention, the sociology of immortality and advancement in artificial intelligence. You will also have the opportunity to interact with our experts as well as share your own views.

We're at a unique turning point in terms of the plausibility of radical life extension. It's not a new idea. Taoists were interested thousands of years ago. 19th Century Russian philosophers talked about physical immortality. Books written in the 1950s and 60s predicted it would happen. But only now is the science starting to look solid. So this is a critical time for people to come together to learn what is happening now and to understand how they can make a difference both in their own lives and in the culture at large. This is the purpose of RAAD Fest, the largest radical life extension event ever.

It's not enough to just talk about possibilities. We need to take all possible actions, including improving diet, exercise, and adopting a positive-and-practical attitude. And we need to influence public opinion to drive more research investment in radical life extension. Action now can be the difference between living and dying. The idea that lifespans are not fixed is being taken seriously by serious people. But we need to bring together the diverse groups involved in radical life extension to have greater impact on public policy. We still spend ludicrous amounts of money on end-of-life care, which is basically extending misery and suffering, when we could be spending it on research that would prevent people from getting in that situation in the first place. We can't afford to have a passive mentality in which we agree in principle, but don't do anything about it. The stakes are too high. We need to come together to celebrate life and to inspire people to take more steps to live healthier lives now, and to take constructive action in society. There's so much that needs to be done. We need to push for changes in public policy, in corporate research funding, and in personal attitudes and cultural beliefs.


Researchers here demonstrate a method of spurring microglia to attack amyloid in mice. It should be said that this is only the latest in a number of approaches shown to clear amyloid and improve symptoms in a mouse model of Alzheimer's disease. Alzheimer's research is an area in which a great many research results fail on moving from mice to people, but that said, there is a lot of independent evidence for microglia to be a useful target in Alzheimer's and other neurodegenerative conditions.

A study has discovered that a protein called IL-33 can reverse Alzheimer's disease-like pathology and cognitive decline in mice. "Alzheimer's disease currently has an urgent unmet clinical need. We hope that our findings can eventually be translated into humans. IL-33 is a protein produced by various cell types in the body and is particularly abundant in the central nervous system (brain and spinal cord). We carried out experiments in a strain of mouse (APP/PS1) which develop progressive AD-like disease with ageing. We found that injection of IL-33 into aged APP/PS1 mice rapidly improved their memory and cognitive function to that of the age-matched normal mice within a week."

The hallmarks of Alzheimer's include the presence of extracellular amyloid plaque deposits and the formation of neurofibrillary tangles in the brain. During the course of the disease, 'plaques' and 'tangles' build up, leading to the loss of connections between nerve cells, and eventually to nerve cell death and loss of brain tissue.‌ IL-33 appears to work by mobilising microglia (immune cells in the brain) to surround the amyloid plagues, take them up and digest them and reduces the number and size of the plaques. IL-33 does so by inducing an enzyme called neprilysin, which is known to degrade soluble amyloid. In addition, the IL-33 treatment worked by inhibiting the inflammation in the brain tissue, which has been shown earlier to potentiate plaque and tangle formation. Therefore IL-33 not only helps to clear the amyloid plague already formed but also prevent the deposition of the plaques and tangles in the first place.‌‌

"The relevance of this finding to human Alzheimer's is at present unclear. But there are encouraging hints. For example, previous genetic studies have shown an association between IL-33 mutations and Alzheimer's disease in European and Chinese populations. Furthermore, the brain of patients with Alzheimer's disease contains less IL-33 than the brain from non-Alzheimer's patients. Exciting as it is, there is some distance between laboratory findings and clinical applications. We are just about entering Phase I clinical trial to test the toxicity of IL-33 at the doses used. Nevertheless, this is a good start."


Researchers here provide a little evidence to suggest that increasing stiffness in muscle extracellular matrix, caused in part by growth in the level of persistent cross-links, explains some of the age-related decline in stem cell activity in that tissue. Removal of cross-links, with the primary target being those involving the advanced glycation endproduct glucosepane, is one of the rejuvenation treatments presently under development within the SENS Research Foundation network of scientists. I expect researchers to ultimately find that the age-related decline in stem cell activity - and all of the signaling involved in that decline - has evolved as a response to levels of molecular damage, rather than as an independent genetic program. Broadly repairing that damage should therefore do a lot to restore stem cell activity, though the stem cells' inherent damage will still have to be addressed as well.

Skeletal muscle aging is associated with a decreased regenerative potential due to the loss of function of endogenous stem cells or myogenic progenitor cells (MPCs). Aged skeletal muscle is characterized by the deposition of extracellular matrix (ECM), which in turn influences the biomechanical properties of myofibers by increasing their stiffness. Since the stiffness of the MPC microenvironment directly impacts MPC function, we hypothesized that the increase in muscle stiffness that occurs with aging impairs the behavior of MPCs, ultimately leading to a decrease in regenerative potential.

We showed that freshly isolated aged myofibers contain fewer MPCs, especially quiescent satellite cells, than adult myofibers. These results were comparable to those of other studies showing that the relative number of satellite cells decreases with age, pointing to a lower rate of self-renewal or to asymmetrical division. We recapitulated the MPC behavior observed on myofibers from adult and aged muscles using stiffness-tunable hydrogels and observed that there was a higher proportion of differentiating MPCs in aged damaged myofibers (18 kPa) than in adult damaged myofibers (2 kPa). This is consistent with the results obtained with MPCs grown on the 2 and 18 kPa hydrogels and indicated that there is a more committed MPC phenotype in aged myofibers. It is possible that an increase in the stiffness to 2 kPa of adult damaged myofibers is beneficial for the activation/proliferation of MPCs. On the other hand, an increase in the stiffness to 18 kPa, as observed in damaged aged myofibers, would be deleterious for the proliferation of MPCs but would favor differentiation. This may be one explanation for the decline in the regenerative capacity of aged skeletal muscle.

A growing body of evidence suggests that the stem cell niche serves as an environment in which stem cells respond to extrinsic stimuli associated with muscle growth and repair and that the mechanisms involved are negatively regulated by aging. As we showed, when MPCs are dissociated from their niche, the proliferation and differentiation potentials of MPCs from aged mice are similar to those of MPCs from adult mice, which lends support to the importance of the MPC niche. The composition of the ECM affects the mechanical properties of the tissue microenvironment, which in turn influences the activity of stem cells. Given that the ECM plays a major role in the increase in stiffness that occurs with age, some authors have suggested that there is a correlation between the increase in collagen deposition and the increase in muscle stiffness, with advanced glycation end-products (AGEs) playing a major role in glycation and collagen reticulation. Changes in the composition of the ECM during aging would thus provide regulatory cues to stem cells, modulating their quiescence, activation, differentiation, and/or self-renewal. In the present study, we confirmed that the increase in collagen deposition in the muscles of aged mice is correlated with an increase in hydroxyproline and AGE levels. These results reinforce the notion that the ECM undergoes qualitative and quantitative modifications with aging that would alter the myofiber repair process.


Researchers here predict future incidence of sarcopenia, the loss of muscle mass and strength that occurs with aging and that is one of the main components of age-related frailty. As the average age of a population rises, incidence, costs, and burden on health will increase, and the costs at least have been something of a concern in political circles in recent years. There is some value in projecting present trends in epidemiology to create dire warnings on future prevalence of age-related disease, even though these trends are already out of date given what is going on in the labs and in early trials. It is a way to increase support for ongoing research to treat and prevent age-related disease, or ideally to intervene in the underlying processes that cause aging, and research funding always needs all the help it can get. In the case of sarcopenia, potential treatments include myostatin inhibition through gene therapy - or other less permanent methods - to spur more muscle growth than would otherwise occur, something that has already shown considerable potential in early human trials, and for which a large body of animal study data exists.

Sarcopenia is a disease associated with the ageing process. Hallmark signs of the disorder are loss of muscle mass and strength, which in turn affects balance, gait and overall ability to perform tasks of daily living. Due to its complexity, there is as yet no global consensus on the definition of the disease for diagnostic purposes. The European Working Group on Sarcopenia in Older People (EWGSOP) has defined sarcopenia as low muscle mass with low muscle strength OR with low gait speed. With two cutoff points available for each of the three components of this definition, eight different methods of diagnosis of sarcopenia can be used.

Using the Eurostat online database, the researchers retrieved age and gender-specific population projections from 2016-2045 for 28 European countries. The age and gender-specific prevalence of sarcopenia was assessed from a study that precisely compared prevalence estimates according to the different diagnostic cutoffs of the EWGSOP proposed definition. The prevalence estimates were interpolated for adults above 65 years of age. The estimates of sarcopenia prevalence were then applied to population projections until 2045. The results showed that using the definition providing the lowest prevalence estimates, the number of individuals with sarcopenia in Europe in 2016 is 10,869,527. This will rise to 18,735,173 in 2045 (a 72.4% increase). The overall prevalence of sarcopenia in the elderly will rise from 11.1% in 2016 to 12.9% in 2045. Women currently account for 44.2% of prevalent cases. Using the definition providing the highest prevalence estimates, the number of individuals with sarcopenia in Europe is 19,740,527 in 2016, rising to 32,338,990 in 2045 (a 63.8% increase). The overall prevalence of sarcopenia in the elderly will rise from 20.2% in 2016 to 22.3% in 2045. Women currently account for 66.4% of prevalent cases.

"Regardless of which diagnostic cutoff is used to define sarcopenia, the prevalence of sarcopenia is expected to rise substantially in Europe. It is therefore essential that we implement effective prevention and disease management strategies. Health authorities must take action in order to limit the impact on increasingly strained healthcare systems and to help Europeans enjoy healthy, active ageing."


Here is a recent example of the more respectful treatment the cryonics industry receives in the popular press these days, though, as ever, the very important differences between freezing and vitrification in terms of their effects on tissues are skipped over. Cryonics providers don't freeze people, they vitrify them, as this offers a greatly improved preservation of fine structures, such as those in the brain that store the data of the mind. Improved methods of vitrification of tissue, with the aim of making it reversible, are in fact under active development by a range of research groups. The goal is use in the tissue engineering and organ transplant communities, to greatly improve the logistics of tissue storage, and I think that growth in that field of research is doing a great deal to change opinions about cryonics.

In the desert climate of Scottsdale, Arizona, rest 147 brains and bodies, all frozen in liquid nitrogen at the Alcor Life Extension Foundation with the goal of being revived one day. It's not science fiction - to some it might not even be science - yet thousands of people around the world have put their trust, lives and fortunes into the promise of cryonics, the practice of preserving a body with antifreeze shortly after death in hopes future medicine might be able to bring the deceased back. "If you think back half a century or so, if somebody stopped breathing and their heart stopped beating we would've checked them and said they're dead. Our view is that when we call someone dead it's a bit of an arbitrary line. In fact they are in need of a rescue." That "rescue" begins the moment a doctor declares a patient dead. Alcor's team then prepares an ice bath and begins administering 16 medications and variations of antifreeze until the patient's temperature drops to near freezing.

"The critical thing is how fast we get to someone and how quickly we start the cooling process," More said. In order to ensure that can happen, Alcor stations equipped teams in the U.K., Canada and Germany and offers members a 10,000 incentive to legally die in Scottsdale, where the record for getting a patient cooled down and prepped for an operation is 35 minutes. Next, a contracted surgeon removes a patient's head if the member selected Alcor's "Neuro" option, as it's euphemistically called, in hopes that a new body can be grown with a member's DNA once it comes time to be thawed out. It's also the much cheaper route. At a price tag of 80,000, it's less than half the cost of preserving your whole body. "That requires a minimum of 200,000, which isn't as much as it sounds, because most people pay with life insurance."

In fact, such a business model is pretty consistent in the nonprofit cryonics community. Michigan-based Cryonics Institute offers a similar payment structure, albeit at the more affordable cost of just 28,000 for whole-body preservation. Which begs the question: Why the price discrepancy? "We've been very conservative in the way we plan the financing. Of that 200,000, about 115,000 of it goes into the patient care trust fund," which is meant to cover eventual costs and is controlled by a board of trustees (a certain number of which is required to have loved ones currently in cryopreservation). The trust currently boasts a total of over 10 million, detailed by Alcor's most recent nonprofit 990 filings.


Hematopoietic stem cells reside in bone marrow and are responsible for producing blood cells, including immune cells. Recent research illustrates one way in which chronic inflammation, important in the progression of degenerative aging, can harm this stem cell population. Since chronic inflammation rises due to immune system dysfunction in aging, mechanisms of this nature may be an important component of negative feedback loops that arise in later stages of aging, in which damaged systems interact to further degrade one another.

IL-1 is a cytokine long understood to be an essential signal the immune system uses to recruit and activate inflammatory cells needed to protect from and repair acute occurrences of infection or injury. However, elevated levels of IL-1 are a feature of chronic inflammation, as is commonly seen in aging, and with a number of disease conditions including obesity and type 2 diabetes, which are associated with Western diet and lifestyle. "Inflammation evolved to function for very short periods of time, marshaling resources to fight infections and repair damaged tissue. However, over long periods of time, these conditions become very toxic. If you're working under a constant state of emergency, you become stressed and less effective. I think of blood stem cells in the same way."

While blood-forming stem cells, also termed hematopoietic stem cells (or HSCs), are usually dormant in the bone marrow, "waking" occasionally to maintain proper blood levels in healthy individuals. HSCs are sensitive to the amount of IL-1 they encounter, and go to work creating "first responder" myeloid cells needed to fight what they recognize as a crisis of infection or injury. If the IL-1 signal doesn't end, HSCs continue making these cells but at the expense of their ability to regenerate themselves and correctly build the rest of the blood system. "They're receiving a signal telling them they need to keep building myeloid cells and as a result they don't make the other blood cells you need. You can end up with too few red blood cells, reducing the body's ability to deliver oxygen to cells. Or we see decreased production of new lymphoid cells, leaving the system potentially immunodeficient. These are all common features of chronically inflamed and even aged blood systems."

Another major question was whether these effects are reversible, in other words, once an HSC has "learned" to overproduce myeloid cells, can it just as readily unlearn this function? To test the durability of the IL-1 insult to HSCs following chronic inflammation, researchers treated mice for 20 days with IL-1 and then took it away for several weeks to see if the HSCs recovered. "Our data suggest that it is possible to turn back the clock and reverse the effects of chronic inflammation on blood stem cells, perhaps using therapies already available in the clinic to block inflammatory signals such as IL-1. Of course, we don't yet know on a human scale how long it takes a stem cell to 'remember' these insults. It may be that after a longer period of exposure to IL-1, these changes become more fixed." Overall, the study demonstrates for the first time that blood stem cells adapt to meet what they recognize as the body's needs, and that chronic inflammation can act like a thumb on the scale, implying a need that does not really exist.


Immunotherapies will clearly make up a large fraction of the coming generation of targeted cancer therapies, but the state of progress is very uneven at this stage, and therapies will still be specific to types and subtypes of cancer - the primary reason why cancer research is so expensive and slow. The use of chimeric antigen receptors is one of the more promising approaches within this class of therapy, not only because it is demonstrating considerable success in initial trials, but also because it can in principle be applied to numerous types of cancer with comparatively little additional work. Here, researchers present initial results from a recent trial:

Twenty-seven of 29 patients with an advanced type of leukemia that had proved resistant to multiple other forms of therapy went into remission after their T cells were genetically engineered to fight their cancers. The immune system is well-known for its remarkable ability to locate, recognize and attack invaders like the common cold. However, the immune system is not always able to eliminate cancer cells when they form. And once malignant tumors develop, they can use a variety of evasion tactics to outwit the immune system. This experimental therapy is designed to overcome some of these challenges, harnessing the power of the immune system to fight cancers by genetically engineering patients' T cells with a synthetic receptor molecule called a CAR (for chimeric antigen receptor) that empowers the T cells to recognize and kill cancer cells that bear a specific marker, called CD19.

This trial was designed to evaluate the safety of administering the engineered cells and to lay the groundwork for future improvements. It enrolled only adult patients with advanced disease that had relapsed or would not respond to other therapies. This paper includes data from 30 participants with B-cell acute lymphoblastic leukemia who received the cells. After patients' T cells were extracted from their bodies, a specialized virus delivered the DNA instructions for making the CAR into the cells. Then, the cells were multiplied to the billions in the lab. After chemotherapy, the now-reengineered cells were infused back into the patients they came from about two weeks after they were first extracted. This study is the first CAR T-cell trial to infuse patients with an even mixture of two types of T cells (helper and killer cells, which work together to kill cancer). With the assurance that each patient gets the same mixture of cells, the researchers were able to come to conclusions about the effects of administering different doses of cells.

In 27 of 29 participants whose responses were evaluated a few weeks after the infusion, a high-sensitivity test could detect no trace of their cancer in their bone marrow. The CAR T cells eliminated cancers anywhere in the body they appeared. Of the two participants who did not go into complete remission, one eventually reenrolled in the trial and went into complete remission after receiving a higher dose of cells. Not all patients stayed in complete remission: some relapsed and were treated again with CAR T cells, and two relapsed with leukemias that were immune to the CAR T cells. It is too early to know what the long-term outcomes of the cell therapy are. "It sounds fantastic to say that we get over 90 percent remissions, but there's so much more work to do make sure they're durable remissions, to work out who's going to benefit the most, and extend this work to other diseases."


Researchers have provided initial and somewhat speculative data to suggest that the decrease in body temperature that occurs in old age may speed the progression of mechanisms implicated in Alzheimer's disease:

"We know that the incidence of Alzheimer's is low before age 65, but doubles every 5 to 6 years afterward. We also know that metabolism and body temperature decrease as people get older. We therefore tested the hypothesis that the changes in the body's thermoregulation that occur with age amplify the main manifestations of Alzheimer's and that a vicious circle can even set in because the disease expresses itself in certain areas of the brain involved in temperature regulation." The researchers used a type of transgenic mice that express the main manifestations of Alzheimer's disease as they age: They produce beta-amyloid, which leads to the formation of senile plaque in the brain; they are affected by a pathology that renders neurons non-functional; and they lose synaptic proteins. In these mice, memory problems begin to arise at the age of 6 months.

By comparing these transgenic mice with normal ones, researchers first established that the transgenic mice were less able to effectively maintain their body temperature as they aged. The difference reached almost 1° Celsius by the age of 12 months. The researchers also observed that the abnormal tau proteins responsible for neuron deterioration increase more in transgenic mice than normal mice, and the loss of synaptic proteins is more pronounced. Conversely, researchers observed that exposure to a high ambient temperature mitigated some manifestations of Alzheimer's disease. After one week in a 28°C environment, the transgenic mice's body temperature had increased by 1°C, beta-amyloid production had dropped substantially, and memory test results were comparable to those of normal mice. "Our findings suggest that it is worth exploring the treatment of thermoregulation among seniors suffering from Alzheimer's."


Here I'll point out a recent study on nicotinamide riboside supplementation in mice. This is a way to increase levels of nicotinamide adenine dinucleotide (NAD), an important player in many aspects of cellular metabolism, particularly mitochondrial function and everything associated with it. Mitochondria are known to be important in aging, either through a decline in their primary function of producing energy stores to power cellular activities, or in the damage they suffer that leads to malfunctioning forms of this cellular component.

Thus far, based on work from the past few years, inducing raised levels of the charged form of NAD, NAD+, in mice appears to be a way to trigger some of the same housekeeping and repair mechanisms as are affected by hormesis and heat shock factors in response to various forms of cellular stress, which is to say that it can modestly slow aging and improve health. Everything is interconnected in cellular biochemistry, so it isn't all at unusual for there to be a dozen or more ways to manipulate any one set of mechanisms. Here the focus is on improved stem cell activity, which is becoming a very common theme in research on aging.

As mice age, the regenerative capacity of certain organs (such as the liver and kidneys) and muscles (including the heart) diminishes. Their ability to repair them following an injury is also affected. This leads to many of the disorders typical of aging. Through the use of several markers, researchers were able to identify the molecular chain that regulates how mitochondria - the "powerhouse" of the cell - function and how they change with age. The role that mitochondria play in metabolism has already been amply demonstrated, "but we were able to show for the first time that their ability to function properly was important for stem cells." Under normal conditions, these stem cells, reacting to signals sent by the body, regenerate damaged organs by producing new specific cells. At least in young bodies. "We demonstrated that fatigue in stem cells was one of the main causes of poor regeneration or even degeneration in certain tissues or organs."

This is why the researchers wanted to "revitalize" stem cells in the muscles of elderly mice. And they did so by precisely targeting the molecules that help the mitochondria to function properly. "We gave nicotinamide riboside to 2-year-old mice, which is an advanced age for them," said the researcher. "This substance, which is close to vitamin B3, is a precursor of NAD+, a molecule that plays a key role in mitochondrial activity. And our results are extremely promising: muscular regeneration is much better in mice that received NR, and they lived longer than the mice that didn't get it." Parallel studies have revealed a comparable effect on stem cells of the brain and skin. So far, no negative side effects have been observed following the use of NR, even at high doses. But caution remains the byword when it comes to this elixir of youth: it appears to boost the functioning of all cells, which could include pathological ones. Further in-depth studies are required.

I'll note that the publicity department that formed up this release should be ashamed of themselves for the title, which is a enormous exaggeration. It is bad enough that the popular press consistently misstates the results of research into aging, when so much of that research produces only small effects, without the allegedly more responsible parties also doing so. Not all longevity science is equal, but when everyone claims to have stopped aspects of aging - when no such thing actually happened - it becomes that much harder for laypeople to gain an appreciation for what is more or less useful in the field.


A gene therapy study carried out in pigs has demonstrated promising results for the treatment of pulmonary arterial hypertension, the form of pulmonary hypertension that involves narrowing of the blood vessels in the lungs. The therapy overexpresses SERCA2a, an approach already under development for the treatment of heart failure. When targeted to blood vessels it can produce remodeling, compensating in part for the narrowing that is the proximate cause of pulmonary arterial hypertension - though without addressing any of the root causes, as is unfortunately still the case in the majority of medical research.

Scientists have used a novel gene therapy to halt the progression of pulmonary hypertension, a form of high blood pressure in the lung blood vessels that is linked to heart failure. Pulmonary arterial hypertension (PAH) is a rare, rapidly progressing disease that occurs when blood pressure is too high in vessels leading from the heart to the lungs. There is currently no cure for PAH, and about 50 percent of people who are diagnosed will die from the disease within five years. The high pressure is caused by abnormal remodeling of the lung blood vessels that sometimes leads to failure of the right ventricle and premature death. Thickening and narrowing of pulmonary vessels is seen with all types of pulmonary hypertension and is triggered by abnormal calcium levels within the vascular cells. The sarcoplasmic reticulum calcium ATPase pump (SERCA2a) regulates intracellular calcium in vascular cells and prevents them from proliferating in the vessel wall.

There were two primary objectives for this study. First, scientists wanted to learn if it is feasible to deliver a therapeutic gene called SERCA2a in aerosol form to damaged blood vessels of the lung using an engineered adeno-associated virus as a "vector." Second, they wanted to see if there was a sustained beneficial impact, and if the transferred genes effectively slowed or stopped the vascular changes in the airways that are the hallmark of PAH and other forms of pulmonary hypertension. The current study is the first to explore this approach in a large animal - specifically, a Yorkshire swine model that closely resembles PAH in humans.

In the study, 20 pigs were divided into two groups, half of which received the aerosolized viral vector carrying the SERCA2a gene and half a saline spray. Two months after the gene delivery, scientists performed tests to see if the new therapeutic genes were present and functioning in the vessels of the animals' lungs, and whether the transfer was producing the desired effects. When they examined the animals, they found that that heart and lung function had improved and abnormal cellular changes causing PH were reduced. Additional animal studies focusing on long-term efficacy and safety are warranted before advancing this approach, known as airway gene delivery, to human clinical trials. That's because the current study involved a small number of animals, and they were assessed just eight weeks after gene delivery. Nevertheless, airway gene delivery appears to modify fundamental pathophysiology, and therefore might offer therapeutic benefit to humans with a variety of pulmonary vascular diseases.


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