Fight Aging! Newsletter, February 1st 2016

February 1st 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:


  • Global Healthspan Policy Institute Launches
  • The Present State of Progress Towards Clearing Glucosepane Cross-Links, a Contributing Cause of Degenerative Aging
  • Coverage of Aubrey de Grey in the Florida Local Press
  • Rejuvenation Biotechnology Update for Q1 2016
  • The Longevity of Tyrannosaurs
  • Latest Headlines from Fight Aging!
    • A Negligibly Senescent Ant Species
    • Combining Cell Replacement and Cell Ablation to Slow Aging
    • Radical Life Extension Discussed at the World Economic Forum
    • A Look at One of the Palo Alto Longevity Prize Competitors
    • On Telomeres and Telomerase in Aging
    • Genetic Associations Between Determinants of Intelligence and Determinants of Longevity
    • Data Mining the Mechanisms of Aging in Nematodes
    • One Possible Approach to a Universal Tumor Vaccine
    • A Potential Therapy for ALS
    • Gene Therapy to Treat Peripheral Artery Disease


The Global Healthspan Policy Institute is a new group that will focus on lobbying for longevity science, primarily in the US, but some of the participating members bring experience from similar efforts in Europe. This initiative is organized by a mix of new faces and folk you might be familiar with from the International Longevity Alliance and other advocacy organizations in the community. For the past few months the GHPI members have been making connections and setting out an agenda in order to take a swing at the same targets as the Longevity Dividend initiative, which is to say (a) recognition of the value of treating aging among the politicians and bureaucrats who set and allocate public funding for research, and (b) greater funding for those lines of research most likely to produce results. At present, that second point largely boils down to more funding for the National Institute on Aging (NIA), though I imagine that once a debate is opened in earnest many more options than that are on the table.

On that second count, I should say that the initiatives to date, such as the Longevity Dividend, fall down badly to my eyes, as open and public support for SENS rejuvenation research has been pretty thin on the ground among those involved in lobbying. This is, of course, setting aside my views on involving government at all in these matters - the net outcome of the package deal of government funding (National Institutes of Health) plus government regulation (FDA) is a negative to my eyes. Public funding for medical research represents perhaps a third of the overall total, but the FDA certainly represents more than a third of the cost of bringing medicine to market, and that isn't even to start in on the way in which regulatory costs remove many lines of development from economic viability, ensuring that countless new therapies are never built.

I'm in a minority with that position, needless to say. The overwhelming majority of the research community support the existing system, even broken as it is, and would rather work to change it slowly through lobbying than bypass it via philanthropy and medical tourism, as would be my preference. Even outside the research world, the sheer size of public budgets has a mesmerizing effect, I think, causing people to forget that tapping them is a corrupting, difficult process that rarely produces the desired outcome. Just ask the molecular nanotechnologists who tried more than a decade ago to obtain US government support for their work as publicity swelled: they were outmaneuvered by existing factions, and their visions derided and spokespeople attacked where that helped said existing factions. Where funds were deployed in alleged support of nanotechnology development, they went to those organizations already well-equipped with lobbyists, and to existing projects that had nothing to do with nanotechnology as defined in the original vision. It was very much a cautionary tale made real.

In any case, it seems clear that we're reaching the point at which a critical mass of people are enthused by the potential for the medical control of aging, and are now ramping up new organizations to engage the political class and sway present streams of funding. The Global Healthspan Policy Institute have allied with the Longevity Dividend researchers, among others, and are readying for their first efforts to obtain more support for aging research in the US political system. Unlike the Longevity Dividend folk, the Global Healthspan Policy Institute principals are at least somewhat more inclined to support SENS rejuvenation research as a strategy based on what I know of them.

Global Healthspan Policy Institute

For the first time in the history of humanity, we're faced with the prospect of a planet where the elderly outnumber the young. As the broken budgets of already strained healthcare systems struggle to cope with this revolutionary shift and the associated burden of degenerative disease, new science tells us we are within reach of healthier, longer lives - while our public policies remain decades out-of-step.

We're leading the charge in bold new policy initiatives on Capitol Hill and around the world, ensuring that policy makers have the tools and resources they need to make the right decision for the people they represent. We invite you to learn more about our mission, principles, and priorities as we take the steps necessary to bring our timely and powerful message to the world.

We are a patient-centered, consumer-oriented public policy coalition and 501c3 nonprofit thinktank working directly with members of the healthspan research industry and scientific community worldwide in support of the large-scale research and development of new treatments to address the underlying causes of aging-related disease. Our direct role is to facilitate the inclusion of all relevant stakeholders in a think tank setting in order to create broader consumer and regulatory acceptance for new treatments relevant to our core purpose of advancing the development of immediate interventions for aging-related disease.

New Thinktank to Promote Research, Innovation for Treatment of Underlying Causes of Aging-Related Disease

A new think tank to support the research and development of innovative treatments for the underlying causes of aging-related disease has been founded in Washington, D.C. The Global Healthspan Policy Institute represents a member network of over 50,000 international supporters. GHPI's present focus is in educating Congress and members of the Administration on the current impact of aging-related disease on public health, well-being, and the economy: (1) Nearly 75% of all U.S. deaths are linked to 9 aging-related diseases. (2) By 2030, the number of U.S. adults aged 65 years or older will more than double, to about 71 million, and Medicare spending will increase by 25% (9 billion). (3) One-third of all Medicare spending (15,000 per person) is tied to aging disease. (4) The economic value of treating the underlying causes of aging-related disease in the U.S. - instead of just one disease at a time - is projected at 7.1 trillion for the next 50 years.

"Medicare and the healthcare systems have spent untold trillions on the 'one disease, one cure, one treatment' model. However, if we address the aging processes that are happening in our bodies right now - and that will lead to a host of new and existing diseases in the future - we can stop these problems before they ever begin, and halt the economic crisis that's bankrupting America. Extending the healthspan, and dramatically reducing the period of compromised living, is now clearly in sight. Longer, healthier living is no longer a hope for the future. It is a reality for the present if we will embrace and invest in the current options that are available to us."


Cross-links are in essence a type of damage resulting from metabolic waste, a natural side-effect of the normal operation of our cellular biochemistry. Many different types of sugary molecules known as advanced glycation end-products (AGEs) end up in the spaces between cells and can react with and link together the intricate structures of the extracellular matrix. The arrangement and constituents of the matrix are what gives each tissue its particular set of properties: elasticity in skin and blood vessels, the ability to bear load without brittleness in cartilage and bone, and so forth. The presence of cross-links in significant numbers sabotages these properties, such as by preventing long, parallel molecular structures from sliding freely past one another. Further, there is evidence to suggest that AGEs produce raised levels of chronic inflammation by altering cellular behavior through the receptor for AGEs, RAGE. Inflammation contributes to the pathology of all of the common age-related diseases.

Most cross-links formed by AGEs are transient, and perhaps only significant in an abnormal metabolism, such as that produced by obesity or type 2 diabetes. The present consensus is that the real problem - leading to age-related loss of skin elasticity and stiffening of blood vessels, among other issues - is produced by a single type of hardy cross-link formed by one type of AGE called glucosepane. Studies suggest that glucosepane makes up the overwhelming majority of cross-links in old humans, and our natural biochemistry is not equipped with tools that can effectively remove these chains.

This is one compound, and to greatly reduce its contribution to aging all that is needed is one moderately effective drug candidate that can break it down. This drug candidate would have as its target market more than half of the human race - pretty much everyone over the age of 30. Yet the broader research community has shown no interest in this goal, an issue we might blame on the lack of tools for working with glucosepane. Any research group diving into this problem would have to build all of the tools from scratch, and that means that near everyone who did take the time to think about it has chosen, again and again, to work on other, more accessible problems instead. This sort of situation requires philanthropy to break the log jam, and thus the only significant funding for glucosepane research in the past few years has come from the SENS Research Foundation, via philanthropists such as Jason Hope, and of course the charitable support of this community.

Nonetheless, because this is a narrow domain problem, the search for one drug candidate for one target, I believe it is the most likely SENS technology to follow on from senescent cell clearance as next in line for commercial development. A method of senescent cell clearance is currently being developed by Oisin Biotechnology, and whatever happens next after that in the SENS space is probably a race between a viable glucosepane breaker drug and transthyretin amyloid clearance, with mitochondrial DNA repair just a few years behind those. However, my knowledge of the latest activity has been getting out of date, so I recently talked to some of the people involved; Aubrey de Grey of the SENS Research Foundation, David Spiegel who runs a lab at Yale, and William Bains who collaborates with an eclectic range of researchers in numerous fields, including this one. What follows is a rough summary of their thoughts on the matter.

A Way to Make Glucosepane is a Big Step Forward

The Spiegel lab developed a reliable way to make glucosepane last year. This is a big deal because people who could not previously collaborate with this type of research can now set up their own studies and investigations. It also ensures that, at least for the foreseeable future, everyone is working from the same definition of what exactly is meant by glucosepane and its particular molecular structure.

There are Still Doubts Over the Glucosepane Consensus

The consensus on glucosepane as the overwhelming majority of relevant cross-links in the process of aging is not airtight - there are growing doubts. It is perhaps reasonable to think that it should be the primary target based on the evidence to date, and Spiegel is optimistic that useful therapies will emerge, but de Grey is cautious, and Bains somewhat unhappy about the poor quality of some past research on this topic. If there was a way to break glucosepane, then doubts could be rapidly solidified or put to rest, but that still lies in the future. The SENS Research Foundation is presently funding research with Jonathan Clark at the Babraham Institute to attempt to ratify that glucosepane is the target, determine whether or not there are other targets, and establish that the present understanding of the structure of glucosepane is in fact the right thing to aim for. Remember that a molecule made of a given set of constituent parts might have a poorly understood shape when folded, these molecules are large and complicated, and shape determines function.

A Drug Candidate Doesn't Exist Yet

There is no drug candidate to clear glucosepane at this time, and not even a speculative idea of where to look for possibilities in the enormous back catalog of existing and explored pharmacology. This lack of direction is a consequence of the lack of exploration of this type of compound in the field. Finding the drug candidate is the big gap that lies between where things stand today and the point at which someone could launch a startup company to finalize a potential glucosepane breaker therapy. The labor required to verify that such a drug candidate works or does not work is modest in comparison to the work of finding such a candidate; this would involve building fairly standard forms of assay to determine levels of glucosepane before and after treatment. One standard approach to this sort of thing would be to equip the immune system with antibodies that react to glucosepane, and then measure the response.

A Drug Candidate Will Most Likely Emerge from Mining the Bacterial World

The Spiegel lab is following the same approach as the LysoSENS research program did over the past decade, which is to search for enzymes in bacteria capable of efficiently breaking down glucosepane. We know they exist because graveyards are not sticky sumps of metabolized sugar. This might actually be discouraging to hear at first, as LysoSENS ran for a decade before transferring the first drug candidates for commercial development by Human Rejuvenation Technologies. However, an enormous advance in the ability to culture bacterial species has taken place in just the past couple of years, an advance not available to the LysoSENS researchers. One of the open secrets of the life sciences used to be that 99% of all bacterial species couldn't be cultured in the lab - but all of a sudden and with a comparatively simple technological advance, that has changed. Everything that bacterial researchers achieved in the past was accomplished with the 1% of bacterial species that were suitable to work with, but now that all bacterial species are fair game, the search space for new molecules has multiplied a hundredfold.

The researchers at the Spiegel lab have already isolated and cultured bacterial species that they are reasonably confident are consuming glucosepane. David Spiegel believes that it might plausibly take two years at the present level of funding to characterize how the bacteria are doing this and whether it involves a simple, single enzyme or something more complicated. If it is a single enzyme, then that can move fairly rapidly to becoming a drug candidate. If not, well, it is probably faster just to look for more bacteria with better candidates. This is a research project that could move faster with more money, as the activities can be carried out in parallel were there more researchers on the staff - but of course raising funds for research in this field is ever a challenge.

Note that I'm glossing over the challenges inherent in picking out enzymes from bacteria and turning them into drugs. There are often unwanted effects, such as triggering of the immune system, that have to be designed out. Many of the options for working around this problem, such as encapsulating drug molecules in a protective sheath, are not practical for something that is intended to get into the tiny spaces of the extracellular matrix. And so on. But these are all challenges that can be addressed, extra work requiring technologies and approaches from elsewhere in the research community to be pulled in.

Two Models for Future Commercial Development

There are two models for commercial development from this point. The first is for an investor with two years of patience, 2 million, and an appetite for risk and uncertainty to come in and fund a company to finish the work started by David Spiegel, William Bains, and Jonathan Clark and their research teams. This sort of thing does happen in many industries, but it is very hard to arrange without deep pockets and good connections. That is why you see this sort of arrangement more often taking the form of a partnership with a pharmaceutical company, as happened for the development of the transthyretin amyloid clearance therapy based on CPHPC.

The other model is to cheer on the researchers, and support them as we can with our donations, for the perhaps few years needed to iron out the doubts about glucosepane, and find a candidate bacterial enzyme. Once they are within striking distance of a proof of concept in mice or rats, then a seed-funded startup could be founded and work proceed from that point. That is much easier to swing for this community - if Oisin managed to obtain seed funding from SENS supporters, then a glucosepane-breaker company could certainly do so to the same level a few years from now.


The SENS Research Foundation seeks to bring an end to aging and age-related disease, and to speed progress towards this goal carries out both research and advocacy. As a part of the outreach conducted by the staff and volunteers, co-founder Aubrey de Grey travels much of the world to give frequent presentations on the SENS approach to rejuvenation research to audiences of all sorts: life scientists, economists, actuaries, students, venture capitalists, advocacy groups, technology convention attendees, TED audiences, and so on. You can find many of these uploaded to YouTube, but there are just as many more that were not recorded at the time. De Grey has been doing this since the turn of the century, and as the opinions of researchers and those who listen to researchers have swayed towards support for treating the causes of aging to extend healthy life spans, the reception in the media has improved greatly. At some point in the last decade, it went from being possible to ridicule any sort of serious longevity science without repercussion to looking like a fool for doing so.

It is well worth noting that little has changed in the underlying science relating to SENS over that time, other than the ongoing progress towards its realization: the list of cell and tissue damage remains much the same, and a person familiar with the topic should have a similar expectation of ultimate success in the medical control of aging through therapies to repair damage whether in 2006 or 2016. What has changed greatly is opinion. There is probably a lesson there in how little consensus matters in comparison to truth and weight of evidence, and how little truth and weight of evidence matters to most people involved in propagating the consensus position. It is something to bear in mind, and it is always worth critically looking at your own beliefs to make sure that they are more than just the party line, for some party, somewhere. The consensus has a way of creeping in around the edges when you are not paying attention.

Today I ran across a couple of articles in the Florida local media resulting from a recent presentation given by Aubrey de Grey. I thought them noteworthy for treating this as just more medical science, something to be discussed respectfully. The times are changing, and as de Grey points out, the near future evolution of this process is one in which the lowest common denominator celebrities are presenting SENS viewpoints on aging and medicine in their own words on prime time television. Once the initial tipping point of about 10% support is reached in the matter of persuading the world to your view, the majority will come around to that view fairly rapidly thereafter. It is pleasing to see this happening.

Scientist envisions perpetual repair process for the human body

The British biomedical researcher Aubrey de Grey, in his quest to press the boundaries of the human lifespan to a point where they essentially no longer exist, often resorts to some provocative soundbites. Like: "Your chance of dying if you're 60 will be the same as your chance of dying if you're 30. That means that most people will live into four digits. Which sounds a bit scary. But get used to it, because it's going to happen." And: "In a worst-case scenario, we might end up having fewer kids than we would like, to make up for all these tedious people who were born a long time ago and haven't had the good grace to die yet." But he also wanted his multi-generational audience this week to understand that he is primarily interested in keeping people healthy.

He described what he called the "sweet spot" between current geriatric treatments that only postpone the deterioration that comes with time, and the elusive ideal of escaping those pathologies through exercise, diet and preventive medicine. He proposed a third approach, which is to repair at certain intervals all the damage that the human body sustains over time, simply by existing. "The idea is that you keep one step ahead of the problem," he said. At the age of 60 or 70, he added, people "will be rejuvenated so that they won't be biologically 60 again until they're chronologically 90."

De Grey referred to the societal implications of life extension as a "side effect" of these future medical technologies, and said he believes those questions are up to our descendants. If we refuse to pursue the possibilities, he added, "We would be condemning a cohort of descendants to the same sort of painful death that our ancestors experienced." After two decades in the field, de Grey believes that consensus in the scientific world is catching up to his own research. "Five years from now," he predicted, "Oprah Winfrey's going to be giving you what I'm telling you. And then you're going to believe it."

Gerontologist tells USF Sarasota-Manatee crowd 'aging' can be reversed

"Tonight I am going to talk about how we are moving forward with research that will lead, in the foreseeable future, to the development of medicines that can rejuvenate the body completely," de Grey said. "In other words, medicines that can repair the molecular and cellular damage the body does to itself in the course of life." Why aren't drug companies on this? "The reason why drug companies are not yet jumping all over this is the same reason they never jump on really early stage drugs," de Grey said. "Drug companies just don't do any drug development anymore in the early stages. We are going to see drug companies jumping on these coming drugs like you have never seen before. We are not going to see it until organizations like the SENS Research Foundation have progressed far enough, however."

Kathy Black, a gerontologist and a professor at USF Sarasota-Manatee, and Paula Bickford, a professor in the department of neurosurgery and brain repair at USF Tampa, gave de Grey an A-plus for innovation and diaglogue-sparking enthusiasm. They downgraded the doctor on some predictions. "I also study aging, and a lot of the things he said about the causes of aging were right on," Bickford said. "I disagree on a few things. You can't just cure arteriosclerosis and everyone is going to live a thousand years. We would have to target all those key things that are changing with aging and I am not sure we are going to be there as soon as he thinks we are."

Black weighed in: "Throughout history the human lifespan has never exceeded about 120. That is the part that I think traditional gerontologists are struggling with. There's a maximum life span for all species, including humans and that's the part we are waiting to see, and we are not quite sure, but innovative thinking and science can take us to places we don't know. So, I don't want to be entirely pessimistic. But I guess I just want to be more cautious." The first 30 extra years don't bother Black and Bickford as much as the next 30 years later, up to 150, they said. "Throughout history that has never occurred," Black said. "That's the one piece we are stuck on but we are willing to travel this road and see." "He's right as far as the areas that need to be targeted," Bickford said. "I just think you would have to target all seven or nine at the same time and maybe even more for this to be put in practice to actually get that 30 years."


The Rejuvenation Biotechnology Update is a collaboration between the Methuselah Foundation and SENS Research Foundation, a newsletter delivered to SENS supporters and members of the Methuselah Foundation 300. The latest edition arrived yesterday, and as usual it is a look at a few of the interesting research results from recent months, with accompanying explanations of their relevance in the bigger picture.

The 300 is a group of donors who have supported the Methuselah Foundation for more than a decade now, and the first members stepped up to help get the first initiatives off the ground back when there were only ideas and intents, longevity science was ridiculed, and funding was scarce. Last year a monument was raised to record the names of the 300, the people who have helped bring about a sea change in the aging research community, the philanthropists who funded the M Prize for longevity science, launched the SENS rejuvenation research programs, delivered seed funding to Organovo, and today support the ongoing New Organ Prizes for tissue engineering. If you want to help speed progress towards a world without aging, in which all age-related disease can be prevented and cured, you could do far worse than to become a member of the 300.

2016 Q1 Rejuvenation Biotechnology Update (PDF)

Transthyretin deposition in articular cartilage: a novel mechanism in the pathogenesis of osteoarthritis.

Transthyretin (TTR) is a protein that normally serves to transport thyroid hormones and the vitamin retinol in the blood. Normally, TTR is dissolved in the blood. However, during aging, some individuals accumulate masses of abnormally folded TTR in their body tissues, a form of amyloid which is associated with impaired organ function. Amyloid aggregates of TTR especially interfere with heart function, and amyloidosis can be fatal in this manner. However, in this study, researchers examined the role that TTR amyloidosis may play in osteoarthritis, a cause of joint pain and inflammation that is common in older individuals. The researchers found that in young individuals, no amyloid deposits were present in the knee joints. Strikingly, however, it was present in 100% of the older individuals with osteoarthritis they examined, as well as in 58% of the older individuals without osteoarthritis in their study.

Although there were only a small number of people in this study, the results are interesting, and underscore the importance of the development of therapies for TTR amyloidosis. TTR amyloidosis appears to contribute substantially to increased mortality at advanced ages. TTR amyloidosis of the heart affects a quarter of those who are age 80 and older, and we are only recently learning that it is also present in other parts of the aging body. Some evidence suggests that TTR amyloidosis may be the main cause of death in individuals over the age of 110. Now, with this study, we can see that TTR may contribute to osteoarthritis too, which implies that a significant increase in quality of life could be obtained - along with potentially increased longevity - if treatments for TTR amyloidosis could be developed. Accordingly, SENS Research Foundation has been pursuing and funding a project to develop catalytic antibodies to break down TTR amyloid deposits.

GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration

There have recently been several exciting reports about the apparent positive effects of GDF-11 in aged animals. A recent paper has reported some observations about GDF-11 that are the opposite of prior reports. It is this controversy which we highlight. GDF-11 is similar in structure to several other proteins, including myostatin (also called GDF-8), a circulating protein which is known to inhibit muscle growth. The current paper of interest alleges that the antibodies used to detect GDF-11 in previous studies were not specific to GDF-11 and were cross-reacting with myostatin. This, the authors allege, led previous investigators to misinterpret the actual concentration of GDF-11 in their experiments. In contrast to these earlier studies, the authors observed an increase in both GDF-11 and myostatin with age using their reagents, and wrote that GDF-11's function is likely redundant with that of myostatin and could be targeted for blockade to treat age related decline in skeletal muscle mass.

This seems like a complicated story with many contradicting results from different groups. It highlights a couple of key points: (1) The importance of scientific dialog and discourse to sort out apparently contradicting results like this, (2) The importance of making sure that research reagents such as antibodies and primers used to detect specific proteins are actually specific for what researchers want to measure, and (3) The idea of a U-shaped dose-response curve for biological molecules, which is one of the many difficulties of trying to tweak metabolism to inhibit the aging process instead of repairing the damage directly.

Once the antibody specificity issue is sorted out, we will need to learn about the true effects of GDF-11 at a range of doses. It is possible that apparently contradictory results were obtained due to different doses of GDF-11 being used in the studies. There may be a "U-shaped" curve of GDF-11 where the optimal amount lies in the middle, and much more or much less could have vastly different effects. Or, it may be that we have yet to discover additional, harmful effects of GDF-11, or that its effects are similar to myostatin as some groups have reported. As with many processes in the body, having too much or not enough of something can have profoundly negative effects, and nothing produced by metabolism is without the potential for harm.


Sometimes I point out research not because it is relevant to the immediate cause of building therapies to control aging, but because it is interesting. That is definitely the case here: I doubt you can find a practical use for a paper on the modeling of aging and longevity in tyrannosaurs. That doesn't stop it from being a fascinating topic, of course.

Researchers follow their interests, and that is worth celebrating. If no-one was interested in deciphering and more importantly treating aging, we would still be in exactly the same position as all of our ancestors: doomed to short lives terminated by a period of pain, suffering, and debility. As things stand we are only maybe doomed, with the odds strongly depending on date of birth and progress in raising funding for research, but even that is an enormous improvement. Whether or not you and I personally make it into the age of radical life extension, by bootstrapping the use of one therapy at a time to incrementally repair our biochemistry and extend healthy life, it remains the case that by supporting this cause we help to create the means to save countless lives in the near future.

Aging is near universal trait among species, and has been for a very long time, all the way back to the murky origins of cellular life. You might look on the universality of aging as the result of an evolutionary race to the bottom, similar in a way to the human relationship with organized violence. War hurts the individual and diverts efforts from productive use, but the only way to survive as a collective when your competitors are proficient at violence is to follow the same path - and so everyone diverts resources into mutual destruction rather than growth. Aging may be such an effective evolutionary strategy because it enables better survival of a species in the face of environmental change. We age because the world changes, and ancestral species with aging replaced near all species without aging, right from the outset. Only in a few scattered niches do we find a tiny number of species where evolution has led to a move away from aging as a strategy. Thus when we look into the deep past and model the lives of species such as dinosaurs, those for which enough bones exist for decent models of life span, we should not be at all surprised to find the same patterns of aging as we see today.

Tyrannosaurs as long-lived species

Tyrannosaurs including Tyrannosaurus rex (shortly T. rex meaning tyrant lizard king) are very popular to the public as well as among paleontologists although they became extinct 66 million years ago. Many mysteries about population ecology and actual behavior of tyrannosaurs have been resolved thanks to modern technologies and collective data in paleobiology. In particular, rigorous anatomic methods have been developed and eventually reliable life tables for tyrannosaurs were estimated. Using their demographic data, tyrannosaur aging dynamics was carefully interpreted. Gompertz function or Weibull function was utilized to quantify tyrannosaur survival curves, but both might be insufficient to appropriately describe complicated biological survival curves. Suitable mathematical descriptions and statistical methods are still required to quantify survival and mortality curves of tyrannosaurs.

Here we address a methodology that enables us to appropriately quantify tyrannosaur survival and mortality curves by utilizing modified stretched exponential survival functions, which we have developed to precisely quantify human demographics. We find a demographic analogy between tyrannosaurs and 18th-century humans despite scale and ecological differences. Interestingly, mortality patterns for tyrannosaurs resemble those for 18th-century humans: probably tyrannosaurs would be able to live so long to undergo aging before maximum lifespans, while their longevity strategy would be more alike to big birds rather than 18th-century humans. We attribute longevity of tyrannosaurs to late sexual maturity, large body size, and rapid growth rate, which would be favorable for longevity.

Analyzing the stretched exponents helps evaluation of longevity strategy across species. Although survival and mortality curves look very similar between tyrannosaurs and 18th-century humans, their stretched exponent patterns are significantly different. The stretched exponents with respect to the normalized age show a clear difference in longevity strategy between 18th-century humans and tyrannosaurs. For 18th-century humans, the curves are similar to those of apes or crocodilians, whereas those of Albertosaurus sarcophagus show similar patterns with deer, cassoway, or raptors. This analysis suggests that tyrannosaurs would live longer than other species in terms of the normalized age. Tyrannosaurs would exhibit late sexual maturity, large body size, and rapid growth rate, which would be favorable for longevity. There would be benefits from predation relief by rapid growth for longevity of tyrannosaurs. Probably becoming giants through rapid growth or becoming apex predators would be favorable to acquire exceptional benefits for releases from predation in early life, which would be good for longevity, regardless of uncertainty on whether they were primarily predators or scavengers.


Monday, January 25, 2016

A small number of species show few or no apparent signs of age-related degeneration across near all of a life span, such as lobsters, naked mole rats, urchins, and so forth. This phenomenon is known as negligible senescence and is of considerable interest to the life science community. Here, researchers provide evidence for an ant species to be negligibly senescent:

Once quick and strong, both body and mind eventually break down as aging takes its toll. Except, it seems, for at least one species of ant. Pheidole dentata, a native of the southeastern U.S., isn't immortal. But scientists have found that it doesn't seem to show any signs of aging. Old worker ants can take care of infants, forage and attack prey just as well as the youngsters, and their brains appear just as sharp. "We really get a picture that these ants - throughout much of the lifespan that we measured, which is probably longer than the lifespan under natural conditions - really don't decline." Such age-defying feats are rare in the animal kingdom. Naked mole rats can live for almost 30 years and stay spry for nearly their entire lives. They can still reproduce even when old, and they never get cancer. But the vast majority of animals deteriorate with age just like people do.

In the lab, P. dentata worker ants typically live for around 140 days. Researchers focused on ants at four age ranges: 20 to 22 days, 45 to 47 days, 95 to 97 days and 120 to 122 days. Unlike previous studies, which only estimated how old the ants were, this work tracked the ants from the time the pupae became adults, so researchers knew their exact ages when putting them through a gamut of tests. The researchers expected the older ants to perform poorly in all these tasks. But the elderly insects were all good caretakers and trail-followers - the 95-day-old ants could track the scent even longer than their younger counterparts. They all responded to light well, and the older ants were more active. Ants of all ages attacked fruit flies with the same level of aggressiveness, flaring their mandibles or pulling at the fly's legs.

Then the researchers compared the brains of 20-day-old and 95-day-old ants, identifying any cells that were on the verge of dying. They saw no major differences with age, nor was there any difference in the location of the dying cells, showing that age didn't seem to affect specific brain functions. Ants and other insects have structures in their brains called mushroom bodies, which are important for processing information, learning and memory. The researchers also wanted to see if aging affects the density of synaptic complexes within these structures - regions where neurons come together. Again, the answer was no. The old ants didn't experience any drop in serotonin or dopamine levels either, two brain chemicals whose decline often coincides with aging.

Monday, January 25, 2016

The authors of this paper propose that suitably tailored periodic destruction of cells combined with cell therapies to replace lost cells could have an impact on many of the forms of cell and tissue damage that cause aging. This is not something that can be achieved today with suitable control over the results at the detail level, but that level of control is a plausible target to aim for in the decades ahead. While looking this over, it might be worth recalling a study published last year in which researchers caused low-quality cells to be continuously destroyed in flies. There is an existing mechanism by which cells compare quality, connected to the triggering of programmed cell death, and the operation of these processes can be adjusted, as was the case in that study. The result was flies that lived 50% longer, an interesting result in this context.

In both biomedicine in general and biomedical gerontology in particular, cell replacement therapy is traditionally proposed as an intervention for cell loss. This paper presents a proposed intervention - Whole-body Induced Cell Turnover (WICT) - for use in biomedical gerontology that combines cell replacement therapy with a second therapeutic component so as to broaden the therapeutic utility of cell therapies and increase the categories of age-related damage that are amenable to cell-based interventions. In particular, WICT may allow cell therapies to serve as an intervention for accumulated cellular and intracellular damage, such as telomere depletion, gDNA and mtDNA damage and mutations, replicative senescence, functionally-deleterious age-related changes in gene expression, accumulated cellular and intracellular aggregates and functionally-deleterious post-translationally modified gene products.

WICT consists of the gradual ablation and subsequent replacement of a patient's entire set of constituent cells gradually over the course of their adult lifespan via the quantitative and qualitative coordination of targeted cell ablation with exogenous cell administration. The aim is to remove age-associated cellular and intracellular damage present in the patient's endogenous cells. Here we outline the underlying techniques and technologies by which WICT can be mediated, describe the mechanisms by which it can serve to negate or prevent age-related cellular and intracellular damage, explicate the unique therapeutic components and utilities that distinguish it as a distinct type of cell-based intervention for use in biomedical gerontology and address potential complications associated with the therapy.

Tuesday, January 26, 2016

A panel session titled "What If You Are Still Alive in 2100?" was held at the World Economic Forum's 2016 meeting last week. I point this out as an indicator of the degree to which the idea of treating aging to greatly extend healthy life spans is percolating into the broader mainstream, with ever more people recognizing both the great opportunity for individuals, as well as the fact that existing institutions of entitlement and wealth transfer fall apart when people live in good health for decades longer than is presently the case. In effect those systems have already failed, are already terrible, fragile, and unethical, and already represent considerable economic risk, but those involved have few incentives to take anything but the most damaging path of ignoring the problem:

Chances are, most of us haven't asked ourselves the question: What if I live until 2100? Most people would probably pin the average human lifespan at somewhere around 70 to 80 years old. But within academia there are some serious discussions being had about what the world will look like when the average person lives past 100. But those discussions are only just beginning to permeate governments and the business world. "What's clear is the major restructuring of life that we think is going to happen with regards to longevity - corporations are not prepared for this. Governments are not prepared for this. It will rest with the individual both working on their own and collectively who will be the agents of change. I expect to see and we are certainly monitoring some amazing experiments occurring over the next decade as people come to terms with what it really means to live 100 years."

It's clear the idea of pushing people out of work at 60 is already behind the times. If we're working longer, we're going to need to keep on learning. So economists think there'll be a shift among people at an older age from a notion of leisure to a notion of recreation. In an elongated life, there will be new life stages. The idea of leisure, work, and retirement will be turned on its head. Individuals will take their own individual paths and have the capacity to transform themselves. The UK government predicts that a child born today will live to 85. That's "obviously ridiculous" but there's a clear reason why governments are sticking to these kinds of estimates, rather than extending life expectancy forecasts to nearer 100. "The reason why they are doing that is that all our pension schemes would go under water and would look more and more like a Ponzi scheme." Corporations and individuals need to realize employees need to work into their 70s and mid-70s - and they'll have to save.

Tuesday, January 26, 2016

The Palo Alto Longevity Prize launched back in 2014, one of a number of research prizes created over the past decade aimed at encouraging greater progress in the application of aging research. This popular press article takes a look at one of the competitors, but note it is garbling the science in a few places. In particular the line on quadrupling mouse life span is probably a reference to a study on a mouse model of multiple sclerosis or similar work on short-lived lineages where any intervention will greatly extend remaining life span by partially fixing the problem that is killing the mice at a young age. Certainly no-one has yet quadrupled remaining life span in normal aged mice - that would be an event echoed around the world.

Researchers say a drug that blocks a protein produced by aging cells in your body could control how fast you grow older. They were contacted by the Palo Alto Longevity Prize to compete against teams from all over the world for 1 million. The protein, known as plasminogen activator inhibitor-1, or PAI-1, normally helps control the body's clot-dissolving system. The scientists believe controlling the protein is a way to prolong life. "The biology of aging is becoming more evident every day that goes by. We're understanding that there are specific changes about cells and tissues as they age, and that there are markers that aging cells make and it's possible to identify those molecules and theoretically slow down the aging process."

The interest surrounding longevity research has grown in recent years, especially after Google announced Calico, a longevity research and development company, in 2013. AbbVie, a pharmaceutical and research company, teamed up with Calico in 2014 to understand the biology that controls life span and ultimately accelerate the availability of new therapies for age-related diseases. In the Palo Alto competition, teams can enter one or both of two categories. The 500,000 Homeostatic Capacity Prize is given to the team that can turn back the clock in a mammal. The second is the 500,000 Longevity Demonstration Prize, which is given to the team that can extend the life span of a mammal by 50 percent. Although the deadline for registration was Dec. 31, the competition will not end until 2019 because different therapies have to be tested. Nearly 30 teams are competing with various approaches like hormone therapy and gene modification.

"I think this competition puts a spotlight on aging, and the fact that this science is advancing very rapidly. We're excited to participate because we think we can make a contribution to the understanding of the aging process in mammals. Almost any disease you can think of is highly dependent upon age." Aging more slowly is especially beneficial to people who have chronic diseases that make their cardiovascular health older than it should be. "Aging is the most important risk factor of heart disease, cancer and neurodegenerative diseases. We all want to have a longer, healthier life span. I don't think people want to live a long time and be infirm, but if you can maintain your vitality and function, I think that's a pretty desirable goal."

Wednesday, January 27, 2016

There is a contingent of researchers who see increased levels of telomerase as a viable therapy to slow aging, and shortened telomeres as a contributing cause of aging. Below find linked an open access paper written from that perspective.

It is certainly the case that genetic engineering of mice to produce additional telomerase results in a modest extension of life, though not as much as initially reported. It seems to generally boost regenerative activity, which results in similar outcomes to stem cell therapies. The primary mechanism associated with telomerase is the lengthening of telomeres, the repeated DNA sequences at the end of chromosomes that act as a counter of cell divisions - a little is lost each time a cell divides and replicates its DNA. While some researchers see shortened telomeres as a cause of aging, it seems pretty clear to me, and others, that average telomere length as presently measured is a reflection of processes of aging, not a cause. There has in the past been some discussion of other ways in which telomerase might be acting on life span, such as by affecting the pace of mitochondrial damage, for example.

In this review, we will discuss the role of telomeres in the origin of age-associated diseases and organismal longevity, as well as the potential use of telomerase as a therapeutic target to delay aging and to prevent and treat age-related diseases. Aging is a multifactorial process that results in a progressive functional decline at cellular, tissue, and organismal levels. During recent years, a number of molecular pathways have been identified as main molecular causes of aging, including telomere attrition, cellular senescence, genomic instability, stem cell exhaustion, mitochondrial dysfunction, and epigenetic alterations, among others. Interestingly, telomere attrition is considered a primary cause of aging, as it can trigger all the above-mentioned hallmarks of aging, although the degree to which it is a principal cause of aging is under active investigation. Critical telomere shortening elicits the induction of cellular senescence or the permanent inability of cells to further divide, which in turn has been proposed to be at the origin of different disease states. In addition, telomere attrition in the stem cell compartments results in the exhaustion of their tissue- and self-renewal capacity, thus also leading to age-related pathologies.

A substantial number of companies are now aiming to harness the knowledge that has been generated, unveiling the molecular mechanisms of aging in order to develop a new class of drugs to prevent and treat the major age-related diseases. In this regard, telomerase overexpression studies in mice have been proof of principle that just modifying a single hallmark of aging, i.e. telomere shortening, this was sufficient to delay not one but many different age-associated pathologies in mice, including cognitive decline. Indeed, the use of telomerase activation in delaying aging-associated conditions has spurred the interest of commercial enterprises.

It is likely that the first clinical use of a telomerase reverse transcriptase (TERT)-based therapy, such as the TERT gene therapy approach developed by us, will be for the treatment of the human telomere syndromes, including aplastic anemia and pulmonary fibrosis. However, this requires the development of appropriate preclinical models and the subsequent clinical trials in humans. In this regard, we have recently generated two mouse models which recapitulate the clinical features of aplastic anemia and pulmonary fibrosis. The disease in both models is provoked by short and dysfunctional telomeres and thus these models provide a platform for further testing of TERT-based treatment strategies for the telomere syndromes.

Given that physiological aging is provoked, at least in part, by telomere shortening, a TERT gene therapy may be used not only for the prevention and treatment of telomere syndromes but also for the treatment of multiple age-related diseases. In this regard, short telomeres have been extensively associated with a higher risk for cardiovascular disease. In support of a potential use of TERT activation in the treatment of age-related diseases, we demonstrated that TERT gene therapy can efficiently rescue mouse survival and heart scarring in a preclinical mouse model for heart failure upon induction of acute myocardial infarction. Collectively, experiments in cell and animal models provide proof of concept for the feasibility of telomerase activation approaches to counteract telomere shortening and its consequences. In particular, the successful use of telomerase gene therapy in animal models of aging and short telomere-related diseases paves the way for the development of therapeutic telomerase treatments in human aging and associated disease.

Wednesday, January 27, 2016

There is a well known association between intelligence and life expectancy, part of a web of related correlations that include wealth, social status, networks of relationships, and education, among others. In the case of intelligence, there is the intriguing possibility that genetics plays a significant role in this statistical relationship with longevity, and effects on life span are not just the results of a greater capability to succeed in obtaining wealth, status, and a consequently better usage of medical technology, for example. This paper points out that some of the same genetic variants influence determinants of both intelligence and mortality:

Cognitive functioning is positively associated with greater longevity and less physical and psychiatric morbidity, and negatively associated with many quantitative disease risk factors and indices. Some specific associations between cognitive functions and health appear to arise because an illness has lowered prior levels of cognitive function. For others, the direction of causation appears to be the reverse: there are many examples of associations between lower cognitive functions in youth, even childhood, and higher risk of later mental and physical illness and earlier death. In some cases, it is not clear whether illness affects cognitive functioning or vice versa, or whether both are influenced by some common factors. Overall, the causes of these cognitive-health associations remain unknown and warrant further investigation. It is also well recognized that lower educational attainment is associated with adverse health outcomes, and educational attainment has been used as a successful proxy for cognitive ability in genetic research.

The associations between cognitive and health and illness variables may, in part, reflect shared genetic influences. Cognitive functions show moderate heritability, and so do many physical and mental illnesses and health-associated measures. Therefore, researchers have begun to examine pleiotropy between scores on tests of cognitive ability and health-related variables. Pleiotropy is the overlap between the genetic architecture of two or more traits, perhaps owing to a variety of shared causal pathways. Originally, the possibility of pleiotropy in cognitive-health associations was tested using family- and twin-based designs. However, now data from single-nucleotide polymorphism (SNP) genotyping can assess pleiotropy, opening the possibility for larger-scale, population-generalizable studies. We aimed to discover whether cognitive functioning is associated with many physical and mental health and health-related measurements, in part, because of their shared genetic aetiology using the recently released UK Biobank genetic data. We curated genome-wide association study meta-analyses for 24 health-related measures, and used them in two complementary methods to test for cognitive-health pleiotropy.

Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer's disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.

Thursday, January 28, 2016

In this day and age, the big advantage provided by conducting studies of aging in short-lived, small species such as nematodes is that it is cost-effective to build increasingly sophisticated processes of automation for such research. Gathering very detailed data on large numbers of individuals becomes possible, and this allows for greater introspection into the mechanisms of aging through statistical methods. The results here are quite interesting, for example, and could not be obtained from mammals given current budgets and constraints on technology:

In order to study life span dynamics at the population level, researchers constructed the Lifespan Machine, a device comprising 50 off-the-shelf flatbed scanners purchased from an office supplies store. Each scanner has been retooled to record 16 petri dishes every hour, totaling 800 dishes and 30,000 nematode worms. The scanners capture images at 3,200 dots per inch, which is a resolution high enough to detect movements of eight micrometers, or about 12 percent of the width of an average worm. The researchers subjected the worms to interventions as diverse as temperature changes, oxidative stress, changes in diet and genetic manipulations that altered, for example, insulin growth factor signaling. The Lifespan Machine recorded how long it took the worms to die under each condition. The researchers then aggregated the data, generated life span distribution curves for each intervention and compared results.

The life span distributions provided considerably more information than just changes in average life span. The research team measured variations arising in ostensibly identical individuals, looking at how many worms died young versus how many made it to old age under each condition. This comprehensive view was important for capturing the dynamics and randomness in the aging process. In one sense, the findings were not surprising: different circumstances produced different life spans. Turning up the heat caused the worms to die quickly, and turning it up higher only increased that rate. Pictured as bell-shaped distributions, certain interventions produced a thinner, high-peaked bell, while others resulted in a more drawn-out and protracted bell.

Despite these obvious differences, the researchers found an unexpected uniformity among the curves. The various interventions seemed to affect the duration of life in the same way across all individuals in the same population, regardless of whether chance or randomness had a short or long life in store for them. No matter which genetic process or environmental factor the researchers targeted, all molecular causes of death seemed to be affected at once and to the same extent. These findings suggest that aging does not have a single discrete molecular cause but is rather a systemic process involving many components within a complex biological network. Perturb any node in the system, and you affect the whole thing.

Thursday, January 28, 2016

More research groups these days are trying to produce treatments for cancer by targeting known commonalities shared by all cancers or at least large classes of different types of cancer. This is good, because the cause of slow progress across the modern history of cancer research is arguably the fact that most efforts focus on approaches that can only work for a tiny fraction of cancer types. When talking about commonalities shared by all cancers, I largely mean lengthening of telomeres via telomerase or the less well understood alternative lengthening of telomeres (ALT) processes. All cancers abuse the mechanisms of telomere lengthening, normally inactive in the somatic cells making up the vast majority of tissues, in order to bypass evolved checks on uncontrolled cellular replication. Telomeres are repeated sequences of DNA at the end of chromosomes that shorten with each cell division, forming a clock of sorts. When they are too short, cells become senescent or self-destruct. If cancer cells are prevented from extending their telomeres, they die. Equally, if cancer cells can be reliably identified through the signature of their abuse of telomere lengthening, then they can be targeted for destruction via any of the selective cell killing mechanisms under development in the cancer research community:

Tumour progression, growth, and metastasis are intimately associated with both increased intratumoural angiogenesis, growth of blood vessels to supply the tumor, and increased cell proliferation. Thus, many therapeutic strategies are focused on targeting either or both of these processes. Angiogenesis, the process by which capillaries sprout from pre-existing blood vessels, is a complex multistep process that is tightly regulated by a large number of angiogenic factors. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) play pivotal roles in tumour angiogenesis.

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, which is silent in normal tissues but reactivated in most human cancers. TERT expression is directly correlated with tumour growth and progression and TERT serves as a universal tumour antigen in immunotherapy for cancer. Immunization against TERT may overcome tumour cell immune evasion by boosting the level of cytotoxic T cells specifically targeting the cancer. Thus, TERT is a promising immunotherapeutic candidate that should be considered for combination with anti-angiogenic therapies.

Antigen-presenting cells including dendritic cells (DCs) express mannan receptors (MR) on their surface, which can be exploited in cancer therapy by designing immune-stimulatory viruses coated with mannan-modified capsids that then bind to DCs and initiate a potent immune response. Co-immunization against tumour (TERT) and angiogenesis-specific markers (VEGFR-2) has a stronger inhibitory effect on tumour growth than single agents. Similarly, immunization of mice with a 1:1 mixture of dendritic cells transfected with VEGFR-2 and TERT mRNAs in vitro was shown to have a synergistic anti-tumour effect. Nevertheless, preparation of antigen-specific DC vaccine ex vivo is costly and time-consuming. A vaccine that directly targets DCs in vivo could be used to bypass these high costs and dependency on ex vivo manipulation.

We previously constructed a mannan-modified recombinant TERT adenovirus as a prophylactic vaccine for targeting DCs. This virus stimulated an antigen-specific cytotoxic T cell response against TERT in mice that was correlated with a clear anti-tumour effect. However, in our subsequent study, we found that the therapeutic anti-tumour efficacy of the vaccine was unsatisfactory. Here, we have dramatically improved the efficacy of this approach by creating a "universal" and effective vaccine, which consists of mannan-modified TERT and VEGFR-2 recombinant adenovirus. The vaccine was tested for its ability to induce anti-tumour immunity in a mouse tumour model. We found that it elicited two kinds of anti-tumour response: an immune cell-mediated attack of tumour cells and suppression of intratumoural angiogenesis. The reduced requirement for ex vivo manipulation and the remarkable synergy achieved by targeting both tumour cells and tumour vasculature suggest that this approach is may be suitable for translation to future clinical studies.

Friday, January 29, 2016

The root cause of amyotrophic lateral sclerosis (ALS) is unknown in most cases, though there are some genetic associations in a minority of patients that suggest possible lines of investigation. The condition is age-related in the sense that it typically emerges in the 50s and 60s. There is no effective treatment at this time and most patients have a short remaining life span of only a few years following onset. So it is good to see the potential for a treatment, not just for the patients, but also because it should help settle the matter of the cause of the condition, how it can be age-related but also occur in only a small number of people:

Researchers announced today that they have essentially stopped the progression of amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, for nearly two years in one type of mouse model used to study the disease - allowing the mice to approach their normal lifespan. The findings, scientists indicate, are some of the most compelling ever produced in the search for a therapy for ALS. "We are shocked at how well this treatment can stop the progression of ALS." In decades of work, no treatment has been discovered for ALS that can do anything but prolong human survival less than a month.

The mouse model used in this study is one that scientists believe may more closely resemble the human reaction to this treatment, which consists of a compound called copper-ATSM. It's not yet known if humans will have the same response, but researchers are moving as quickly as possible toward human clinical trials, testing first for safety and then efficacy of the new approach. ALS was identified as a progressive and fatal neurodegenerative disease in the late 1800s. It's known to be caused by the death and deterioration of motor neurons in the spinal cord, which in turn has been linked to mutations in copper and zinc superoxide dismutases.

Copper-ATSM is a known compound that helps deliver copper specifically to cells with damaged mitochondria, and reaches the spinal cord where it's needed to treat ALS. This compound has low toxicity, easily penetrates the blood-brain barrier, is already used in human medicine at much lower doses for some purposes, and is well tolerated in laboratory animals at far higher levels. Any copper not needed after use of copper-ATSM is quickly flushed out of the body. Experts caution, however, that this approach is not as simple as taking a nutritional supplement of copper, which can be toxic at even moderate doses. Such supplements would be of no value to people with ALS.

Using the new treatment, researchers were able to stop the progression of ALS in one type of transgenic mouse model, which ordinarily would die within two weeks without treatment. Some of these mice have survived for more than 650 days, 500 days longer than any previous research has been able to achieve. In some experiments, the treatment was begun, and then withheld. In this circumstance the mice began to show ALS symptoms within two months after treatment was stopped, and would die within another month. But if treatment was resumed, the mice gained weight, progression of the disease once again was stopped, and the mice lived another 6-12 months. "We have a solid understanding of why the treatment works in the mice, and we predict it should work in both familial and possibly sporadic human patients. But we won't know until we try."

Friday, January 29, 2016

Peripheral artery disease is a narrowing of blood vessels in the limbs, usually caused by the progression of atherosclerosis, and consequent failure to deliver enough oxygen to cells. Tissues fail to heal and grow, and ultimately die, causing serious medical conditions along the way. Here researchers are trying a more sophisticated form of patch therapy, not addressing the root causes, but altering the signals delivered to cells in order to create greater growth and regrowth in blood vessels. This has the potential to partially compensate for the progression of blood vessel narrowing, but like all compensatory approaches it can only buy a little time, not fix the problem:

The study examined the safety and efficacy of gene therapy with a plasmid DNA containing human hepatocyte growth factor (HGF) gene, called VM202, in 52 patients with critical limb ischemia (CLI), a severe form of peripheral artery disease. The HGF gene in VM202 produces two isoforms of HGF proteins that are naturally found in the human body. HGF is a growth factor that induces angiogenesis and acts as a neurotrophic factor. After VM202 is injected into a patient's muscle, it is taken up by a cell and produces the HGF proteins, which are then released from the cell and may induce new blood vessel formation by activating various signaling pathways. In this way, VM202 may provide clinical benefits to CLI patients.

VM202 was found to be safe and well tolerated and showed clinical benefits in CLI patients who had no other treatment options. Both ulcer healing and tissue oxygenation improved significantly in patients who were given four series of VM202 injections (spaced 2 weeks apart) in the muscle of the diseased leg. "We are looking forward to conducting a phase III trial to better understand the potential of this novel approach, especially in treating non-healing ulcers, which is a serious symptom that often leads to amputation because of the lack of medical therapies available."

In the study, patients treated with high-dose (16 mg total) VM202 showed significantly better ulcer healing than did patients who were treated with placebo injections. In fact, 62% of ulcers treated with high-dose VM202 healed completely compared with only 11% of ulcers treated with placebo. Statistically meaningful results were also seen in tissue oxygenation (TcPO2 levels). Of patients treated with high-dose VM202, 71% showed increased TcPO2 levels, whereas only 33% of control patients showed better tissue oxygenation.


Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. 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.