Fight Aging! Newsletter, June 29th 2015

June 29th 2015

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

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  • The Heart is a Strange Sort of Organ
  • Considering Peto's Paradox
  • Today and Tomorrow in Tissue Engineering
  • Longevity Drives Economic Growth
  • 2015 Summer Scholars at the SENS Research Foundation
  • Latest Headlines from Fight Aging!
    • A Perspective on Long Term Risk in Cryonics
    • More Data on the Longevity of Elite Athletes
    • Highly Effective Therapies for Single Cancer Types Should be Expected in the Near Future
    • Has Aging Ever Been Considered Healthy?
    • A Prototype Artificial Neuron Capable of Relaying Neurotransmitter Signals
    • An Update on Prosthetic Vision
    • Evidence for Memory to be Stored in Synapses
    • To What Degree is Behavioral Change in Aging Driven by Specific Forms of Neurodegeneration?
    • Trametinib Modestly Extends Healthy Life Spans in Flies
    • Changing the View of Aging: Are We Winning Yet?


All organs are of course very different from one another, but some are more unusual than others. The heart is largely muscle, but muscle with strange characteristics, one of which is that it does an exceptionally poor job of regeneration following injury. This isn't what you'd like to hear regarding the second most vital organ in the body. As is also the case for the brain, it was only comparatively recently established that the adult heart generates any meaningful number of new replacement muscle cells over time. That flow of replacements is small enough and slow enough that even in old age it is still the case that most of your heart muscle cells were originally created in early childhood. The important thing for researchers in the field of regenerative medicine is that this flow exists at all, however. Given a natural process there will be ways to expand upon it, but this is still very young research even in comparison to similar investigations of ways and means to expand the trickle of neurogenesis in the adult brain.

Current first generation efforts to spur heart regeneration through stem cell therapies skip over all of these subtleties in a brute-force attempt to heal, but regenerative medicine is a field in which the numerous differences between organs matter greatly. Research groups tend to specialize on just a few tissue types at a time, hammering out protocols and knowledge needed to induce regeneration, none of which have immediate application to healing in other tissues. It is similar to the situation in cancer research, in which every cancer is radically different in the ways that matter, but with less of a hope of finding common points of action that should work in many different tissue types. Building tissue is always going to be harder than destroying tissue, and there will be far fewer shortcuts: it is the nature of things. Thus the development of regenerative medicine that builds upon, and eventually goes beyond, stem cell research will be a large and costly field of many specialties for decades. It heralded the start of the era in which degenerative aging will be effectively treated, and I imagine it will still be going strong and with much to accomplish well after the first suite of SENS-like rejuvenation treatments are commercialized.

Back to the heart, here are a couple of recent papers that look at the unusual dynamics of heart cells, particularly in heart muscle tissue:

Most heart muscle cells formed during childhood

New human heart muscle cells can be formed, but this mainly happens during the first ten years of life, according to a new study. Other cell types, however, are replaced more quickly. During a heart attack, when parts of the heart muscle are starved of oxygen, many heart cells die and are replaced by scar tissue. As this impairs functionality, many researchers are interested in the possibility of stimulating the regeneration of lost heart muscle cells. But is it possible?

To examine the regeneration of human heart cells, the team behind this new study used a combination of methods. One such was to measure the radioactive isotope C-14, exploiting the sharp rise in atmospheric levels of carbon-14 in the 1950s and 60s caused by nuclear testing. Levels then declined, which means that cells that were formed after that period give lower C-14 readings than those formed during it. Thus by measuring the amount of C-14 in a cell's DNA, the researchers were able to calculate its age. "We examined the heart tissue from 29 deceased individuals of various ages and found that even by one month after birth, the heart contains the same number of cells as it has in adults."

According to the study, the heart grows during childhood because its cells increase in size rather than in number; in other words, heart cells are generated on only a modest scale, and even during a long life, only forty per cent of muscle cells are replaced. "Our findings suggest that it can be rational and realistic to develop new therapeutic strategies for strengthening the body's own regenerative capacity to treat heart diseases."

Telocytes and putative stem cells in ageing human heart

Tradition considers that mammalian heart consists of about 70% non-myocytes (interstitial cells) and 30% cardiomyocytes. The presence of telocytes has been overlooked, since they were described in 2010. Also, the number of cardiac stem cells has not accurately estimated in humans during ageing. We used electron microscopy to identify and estimate the number of cells in human atrial myocardium. Three age-related groups were studied: newborns (17 days - 1 year), children (6-17 years) and adults (34-60 years).

We found that interstitial area gradually increases with age from 31.3 ± 4.9% in newborns to 41 ± 5.2% in adults. Also, the number of blood capillaries (per mm2) increased with several hundreds in children and adults versus newborns. Cardiomyocytes are the most numerous cells, representing 76% in newborns, 88% in children and 86% in adults. Interestingly, no lipofuscin granules were found in cardiomyocytes of human newborns and children. The percentage of cells that occupy interstitium were (depending on age): endothelial cells 52-62%; vascular smooth muscle cells and pericytes 22-28%, Schwann cells with nerve endings 6-7%, fibroblasts 3-10%, macrophages 1-8%, telocytes about 1% and stem cells less than 1%.

We cannot confirm the popular belief that cardiac fibroblasts are the most prevalent cell type in the heart and account for about 20% of myocardial volume. Numerically, telocytes represent a small fraction of human cardiac interstitial cells, but because of their extensive telopodes, they achieve a 3D network that, for instance, supports cardiac stem cells. The myocardial (very) low capability to regenerate may be explained by the number of cardiac stem cells, which decreases fivefold by age (from 0.5% to 0.1% in newborns versus adults).


Cancer is a numbers game, caused by just the right mutationnuclear DNA constantly: you can't put a bunch of complex molecules in close proximity without frequent breakage, and that's even without considering the fact that portions of a cell are involved in the energetic business of converting nutrients into energy stores, a process that generates reactive molecules as a byproduct, or that cells are frequently stressed by heat or exercise. A great deal of a cell's complexity is in fact due to the panoply of mechanisms required for ongoing detection of damage, recycling of damaged components, and building replacement parts as needed. This is a continual process, always attempting to keep up with the pace of damage. Of course all of those mechanisms are also vulnerable to damage and must therefore be capable of repairing themselves, but no repair process is perfectly efficient. DNA repair machinery is some of the most efficient of all of these mechanisms, but it still lets things through: there are so many cells in the body that even a tiny failure rate leads to unrepaired damage.

Fortunately most of the time this just means that at worst a cell will falter or break. Most cells are temporary parts of their tissue, and will die off within days or weeks to be replaced by others. A mutated cell with a more serious breakage may become senescent, removing itself from the cell cycle of replication, or destroy itself. Even in the situation of a potentially cancerous mutation, the cell will still most likely be destroyed by the immune system or its own defenses. But again, there are a lot of cells in the body. It only takes one to slip through all of the layers of defense to start up a tumor. You can develop cancer at any age - you just have to be very unlucky for it to happen in youth, when there is little damage and all of the repair and defense mechanisms are operating a peak efficiency. Later on is a different story, of course, and cancer is an age-related disease because the odds get progressively worse with increasing tissue damage and a growing failure of repair machinery and immune surveillance.

So as I said, this is a numbers game. Count the cells, multiply by mutation rates, and divide by repair efficiency - and there is the scaling factor for your odds of cancer. Or at least in theory, from a naive point of view. Yet here is an interesting thing: mice are little cancer factories in comparison to humans. Yet we humans have thousands of times as many cells as a mouse. Further, what about whales? They have thousands of times as many cells as we do, and some of them seem capable of living twice as long as we do. Yet they don't seem to have any significantly greater cancer incidence. If you compare across other mammals, it turns out that there really isn't any correlation between body mass and cancer rate. This observation is known as Peto's Paradox, proposed with the idea that there is evidently more to the cancer numbers game than first thought.

The motivation for researchers is to be able to identify the differences that exist in the biochemistry of large mammals to explain why they don't have very high cancer rates. There is presumably some chance that this research could result in therapies for humans, though the odds are unknowable in advance. Any sort of investigation of other species could turn up differences that are near impossible to apply to human biochemistry, or differences that could soon lead to therapies, and it's next to impossible to put real numbers to those odds without further research. Still there has been some progress on the basics in recent years, and this open access paper is an example of present thinking on the topic.

Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis

It is an open question why an elephant, with 100× more cells than a human, or a whale with 1000× more cells than a human, has approximately the same (or lower) cancer risk as a human. This is Peto's paradox, and though many potential solutions have been proposed, it remains unsolved. The fact that cancer rates are approximately constant across body sizes and lifespans suggests that there has been selection on the life histories of organisms to prevent cancer in large, long-lived organisms. In order to investigate Peto's paradox, it would be helpful to understand how much evolution would have to change the parameters of somatic evolution to compensate for the evolution of large bodies and long lifespans. For example, we can ask how much the somatic mutation rate must decrease in order for a whale, which has 1000× more cells than a human, to retain the same cancer risk as a human.

There is still much work to be done in the field to obtain more accurate estimates of human somatic mutation rates, as reported values span orders of magnitude. Though the estimates are not perfect, slight differences in mutation rate across species have been observed. For example, one study that derives somatic mutation rates from specific loci across eukaryotes found that the per base mutation rates for human and mouse are a factor of 3.6 apart. This 3.6-fold decrease in mutation rate in human versus mouse is remarkably close to the results of our modelling, which suggest that a two- to threefold decrease in mutation rate can account for a 1000-fold difference in body size between mice and humans. This effective decrease in mutation rate may be accomplished by having better DNA repair in the larger species, more efficient removal of mutated cells, or less endogenous damage as a result of a lower mass-specific basal metabolic rate.

Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. We surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans.


In this post, find some thoughts on costs and risks in the future of regenerative medicine and organ engineering, as well as a pointer to a recent Nature article on the field of tissue engineering. By all accounts researchers have come a long way in the past decade towards the goals of new organs on demand, perfect healing of any injury, and restoration of age-damaged tissues. The reward for all that has been achieved to date is a clear view ahead to show that a great deal more is left to be accomplished. Progress continues, however, and the regenerative treatments and transplants of the next decade will look like the science fiction of past generations - as is only right.

Consider that the shape of the technology landscape is at root determined by costs. After scientists in any given field are far enough beyond fundamental research to understand the bounds of the possible for the next twenty years, research programs then tend to aim downhill at the implementations and outcomes that cost less, are more efficient, and cause less trouble. Why aim to build something that will be an expensive source of problems and few benefits when you don't have to? Of course no group of humans are completely rational, but over the long term economic incentives usually win out.

This is just as true for tissue engineering as for any other field of research and development. A great deal of effort is presently going towards the ability to create organs on demand, with the primary focus neing on decellularization: not growing organs from scratch, but taking a donor organ, possibly not even human, clearing out its cells, and replacing them with new cells derived from a patient. As an implementation this will be a great improvement over the present state of organ transplantation. Yet in the grand scheme of things this is all still a highly expensive, risky, and traumatic set of medical procedures. Organ replacement is major surgery, and major surgeries require highly trained medical teams, extended hospitalization, and an attendant risk of death. This is the standard because there is no better alternative today.

So consider this picture of cost and risk for a moment. It really doesn't seem likely that the advances in tissue engineering needed to be able to grow patient-matched organs from a small skin sample, taking place between now and the 2030s, will then be coupled with extensive transplant surgeries. It's a viable approach in the case of the comparatively rare traumatic accidents suffered by young and robust people, but just won't work as a way to address the consequences of degenerative aging across the entire population. You won't see organ factories churning away to support the old, while everyone undergoes many complex surgeries in their 60s and 70s. It is impractical: excessive cost, excessive risk. We can think about the outer limits of the possible given the ability to regrow any organ, but it seems unlikely that full body replacement or other science-fiction staples will actually happen as a matter of course, rather than being a rare and risky attempt at saving a life when nothing else can possibly work.

Much more likely is that the very same progress in biotechnology that allows for the construction of patient-matched organs from scratch will also allow for considerable regeneration of age-damaged organs in situ. It is all a matter of control over cells, their states, and their signaling to produce a coordinated reconstruction of tissues. This would have to be coupled with other rejuvenation treatments to clear out accumulated metabolic waste in tissues, such as cross-links, lipofusin, and amyloid, and repair other forms of damage in long-lived cells that remain in place throughout the treatment. The business of repairing organs in place, especially those that do not naturally regenerate all that well such as the heart, is probably going to be more complex to achieve than clearance of waste, however. If there is anything that today's investigations into regeneration can teach us, it is that all cellular activities are exceedingly complicated.

The cost in the case of in situ regeneration is a very different picture from that of transplantation. In place of surgeries, hospitalization, and exceedingly expensive medical teams you have mass-produced infusions carried out in out-patient clinics, coupled with diagnostic tests to monitor progress. This is more than an order of magnitude less expensive if you look at today's medical costs for similar treatments, and further the risk of death and complication is far less pronounced. So bear this all in mind when looking at the state of tissue engineering today:

Tissue engineering: Organs from the lab

In their quest to create organs in the laboratory, researchers have come a long way. Engineered tissues are already used in medical research and have even entered clinical trials. But they are much simpler than the real thing. To make a stomach, a lab might use 3D printing to create a mould that could be seeded with the appropriate cells. But without cues provided by blood flow and interactions with other tissues, the result would be simply a stomach-shaped statue, unable to digest or growl. An organ is much more than a mass of cells arranged in a particular configuration: it also has support scaffolds, blood vessels to deliver nutrients and signal molecules, and a hierarchy of intricate control functions that can respond to internal and external cues.

All this makes it tough to build a functional, physiologically relevant organ in the lab. But tissue engineers are making inroads into the problem. To try to tackle the biological complexity of organs, they can choose from various fabrication approaches. One method is to place cells into elaborate, but still simplified models of an organ the size of a microscope slide, which can then be connected together to probe how organs interact. These miniature 'organs-on-chips' provide a unique vantage into organ function and disease, and for applications such as toxicity tests of drug candidates. An alternative approach is to foster the ability of cells to self-assemble, in the hope that they will recapitulate actual organ development and reveal insights into the process.

Whatever the strategy, researchers can start with biologically simple approaches, and then add complexity to the model a little at a time. Just how similar an artificial version of an organ needs to be to its original depends on the questions that are being asked of it. Artificial organs may look very different from their in vivo counterparts but nonetheless be useful for drug testing and basic research. Whether the goal is to understand an organ or to replace it, the eventual aim is an engineered system that functions as reliably as the real thing. Researchers across the world are using these systems to address a wealth of important questions. They can, for example, help to reveal how cancer cells detach from a tumour to invade other tissues, and allow scientists to recapitulate processes in disease and development, such as what might go awry in neurodevelopmental disorders.

Ultimately, the usefulness of the tool is what is important, not the specific approach that is chosen. Engineered tissues are starting to allow incisive experiments and even replacement therapies. And perfectly mirroring nature may not, in all cases, be what is needed. What is critical is that the organ has enough complexity to accomplish its function. Whether it be a patch for damaged hearts, a better toxicity test or an insight into a devastating brain disease, tissue engineering delivers what scientists crave: more understanding, and the potential to help people.


Economic growth is fetishized in modern society, an idol and a yardstick. This shouldn't be surprising given the benefits that accompany the wealth of a society, amply demonstrated within the span of a lifetime for many countries in Asia and Africa, as entire populations moved rapidly from a state of agrarian poverty to build far wealthier industrial societies. It is argued here that rising life expectancy is a principal driver of economic growth, not just a benefit of increased wealth, and given this we should expect to see interesting times ahead of us.

It is arguably the case that the Industrial Revolution happened where it did and when it did in part due to a few generations of small but steady increases in life expectancy. This drove a slowly compounded increase in wealth and technology, which in turn fed back into further increases in life expectancy, and over time this small difference between England and the rest of Europe grew large enough to be the economic basis for a suddenly rapid expansion in technology and prosperity. Progress is the consequence of investment, and investment requires wealth. The growth curve is exponential, a bootstrapped grind from nothing that accelerates and feeds on itself as progress produces wealth that drives progress.

But why does longevity improve economic growth? Firstly because people who expect to be around for longer have more of an incentive to invest in improving the state of their property over the long term, and that happens to coincide with what should be going on if the goal is to create greater wealth for all. Short term thinking is the great destroyer of prosperity. Secondly age-related disease and disability imposes huge costs, both direct and opportunity costs: the sick must be cared for, and the productive work they could have carried out now goes undone. When people die, their knowledge and their contributions are lost. The cost of this lost human capital is staggering, should you actually sit down to run the numbers.

Increased life expectancy in past centuries was largely a matter of raising the average age at death through better nutrition and control of infectious disease, as well as other improvements in the provision of medicine, such as greater availability of any sort of worthwhile medical services. This was a matter of reducing mortality rates in childhood and early adulthood more than anything else. The future will be quite the opposite, and indeed even today the causes of the upward trend in life expectancy are quite different from those of the 17th and 18th centuries. We will live to see large gains in life expectancy arriving in later life, produced by addressing the causes of aging so as to create rejuvenation and extended vigor.

The effects on economic growth should still be just as profound over time. If stewardship of property is greatly improved by life expectancy at birth growing from 40 to 80, and the costs of aging and disease reduced, then the economic outlook improve again when the expectancy for health life span pushes towards 200 and beyond. I say beyond because if anyone alive today makes it that far, then so much technological progress will have occurred that the state of biotechnology should enable indefinite health by that time. There is no upper limit on human life span given sufficiently capable therapies to repair the causes of aging, and we are now moving into an era in which researchers are just starting to look at doing this, as opposed to patching over the consequences and hoping for the best.

The Longevity Dividend from an Aging Population

Indeed, a central issue with America's aging population - driven by longer lives, lower birth rates and the graying of 78 million baby boomers - is the question of how to manage a society with as many old as young. This is fundamentally a question of economics. The question for all of us is how to square 21st century aging populations with misaligned 20th century policies. Investing giant BlackRock recently addressed this challenge in a white paper and related panel discussion in New York. BlackRock, which manages trillions in assets and serves 89% of the largest U.S. retirement plans, brings a compelling set of new ideas to the table.

The most remarkable thing about the new BlackRock report, "Unlocking the Longevity Dividend: How Longer Lives Are Changing Retirement, Investing and the Economy," is that it's not another woe-is-us lamentation on how demographics are going to doom America and the world. Instead, the report argues that if we get things right, longevity and population aging can be a lever of growth for individuals, families, businesses and nations - essentially, everyone on the planet.

BlackRock gets it right by focusing on the fundamentals of human capital: "Longer lives have created a vast pool of experience, capability and wealth that can become a driver for 21st century economic growth. Indeed, the transformative power of the generation now entering retirement should come as no surprise: Baby Boomers, born in the two decades following World War II, have reinvented every phase of life they have entered, often by design and sometimes through sheer force of numbers and economic clout."


In this post you'll find pointers to the profiles of some of the SENS Research Foundation summer scholars for 2015. These talented young scientists are placed in influential labs for the summer to work on research relevant to the goal of treating aging and age-related disease. Cultivating today's young academics is the starting point for building the dedicated, enthusiastic research community of tomorrow, the people who will usher in the rejuvenation therapies of the 2030s and beyond.

At the very best possible pace of development, a pace that would require considerably more funding for the relevant research than is presently the case, it will likely be another twenty years before the first comprehensive package of rejuvenation therapies are in the final stages of development, on the way to the clinic. Unless the funding situation dramatically improves in the next few years, the likely timeline is longer: most of today's research interest in the treatment of aging as a medical condition goes towards research programs that cannot possibly produce actual rejuvenation, and can at best only modestly slow the pace of aging. Yet the cost in time and money for that course will likely be much greater than for attempts to create rejuvenation by repairing the causes of aging. It is frustrating, one of many things that must change if we are to see meaningful progress towards an end to aging.

The people who will lead laboratories and found startups at the time of the first commercial rejuvenation treatments are in the final years of their academic biotechnology studies today. Whether or not tomorrow's leaders choose to enter the aging research field is something that we can influence today. For many decades aging research has been the poor cousin in medicine, thought of as a dead-end, ill-funded area of research. Yet this is far from the case: aging research today is a hotbed of cutting-edge molecular biology, rich with potential, and I think it no great exaggeration to say that medical control over degenerative aging will grow to become the principal pillar of medicine in the later decades of this century. There are names and fortunes to be made in the years ahead, but that all starts with education: showing the students of today that work on aging is a great choice for a life science career, and helping them to make connections in the research community and related industries that will serve them well in the years ahead.

As for any human endeavor, a research community doesn't just spontaneously emerge from nothing. It must be cultivated. This is an important aspect of the work of organizations like the SENS Research Foundation. It's not just a matter of funding and coordinating the right research today, but also ensuring that a community of enthusiastic scientists exists to carry that work through to completion in the decades ahead. Thus the SENS Research Foundation runs a yearly placement of talented young scientists in their Summer Scholars program, sending them out to some of the most noted laboratories in the US. Some of this year's crop are profiled:

2015 Summer Scholar Profile: Amanda Paraluppi Bueno

I am very excited to work for SENS Research Foundation because I will have the chance to learn and contribute to research centered around the diseases of aging at the Wake Forest Institute for Regenerative Medicine (WFIRM), which is an extraordinary place for this field. This summer, my Principal Investigator is Dr. Graça Almeida-Porada and my mentors are Saloomeh Mokhtari and Steven Greenberg. Our goal is to develop novel cell-based therapies that could provide a curative treatment for Inflammatory Bowel Disease (IBD).

The Almeida-Porada lab has already shown that increasing the expression of immunomodulatory molecules on mesenchymal stem cells (MSC) leads to better immunosuppression and improvement of IBD in a murine model. Other cells that could help in the treatment of the gut inflammation are endothelial progenitor cells (EPC). These cells are known to increase the vascularization in ischemic tissues. Therefore, EPC could help normalize vascularization in the intestinal submucosa of IBD patients. Hence, I plan to treat IBD in mice using MSC and EPC as cell therapy to promote the modulation of the immune system and increase the vascularization in the intestine.

2015 Summer Scholar Profile: Blake Johnson

I first became interested in the field of regenerative medicine after viewing Dr. Anthony Atala's TED Talk on his 3-D kidney printing work. The ability of regenerative medicine to be applied to a vast array of cells, tissues, and organs and the possibility of making patients truly well again, as opposed to managing symptoms, is inspiring. WFIRM is an outstanding research institution, and it is an honor to have been selected to spend the summer learning and growing here.

This summer, I am working under the direction of Dr. John Jackson to generate thymus organoids capable of producing functional T-cells. The thymus serves an important function as the site of T-cell development. Interestingly, as we age, the thymus undergoes involution, or decreases in size, leading to a decrease in naïve T-cells. The ability to generate a functional thymus outside the body would have a number of clinical applications, including rejuvenation of an aging thymus to boost the immune response in older individuals and development of tolerance in organ transplantation.

2015 Summer Scholar Profile: Le Zhang

This summer, I will be conducting my research project in Dr. Jeanne Loring's laboratory at the Center for Regenerative Medicine in the Scripps Research Institute. The Loring lab has derived dermal fibroblasts from 10 patients with Parkinson's disease. These fibroblasts have been reprogrammed to induced pluripotent stem cell (iPSCs), which have been differentiated into midbrain-specific neural progenitor cells. These cells will later develop into dopaminergic neurons after transplantation. The Loring lab is the first lab conducting iPSC transplantation on Parkinson's disease patients, so it is essential to ensure genomic stability of the cells being transplanted. An important method to determine genomic integrity of patients' iPSC lines is single nucleotide polymorphism (SNP) genotyping, which can be used to examine millions of single base pair differences at genomic sites specific to humans.

SNP analysis will enable me to determine if the cell populations are suitable for transplantation or whether they have too much genetic change and, hence, potential risk for tumorigenesis. My research this summer will generate and analyze genomic SNP profiles from patient-specific dermal fibroblasts, iPSCs, and neuronal progenitors. SNP patterns from the three cell types will be compared to determine whether genomic instability has occurred from fibroblasts to iPSCs then to neuronal progenitors. Hopefully, with efforts from other scientists and me, the Loring Lab will successfully identify some cell lines that are suitable for transplantation and pass the FDA approval.

2015 Summer Scholar Profile: Zeeshaan Arshad

Under the mentorship of Professor Chas Bountra and Dr. David Brindley, my project will propose a model of open innovation in the translation process to address the problem of developing Alzheimer's disease drugs. To do this, I will use a model to compare open innovation to more conventional drug development strategies by measuring certain metrics to determine the effect open innovation has on each stage of the translation process. These metrics can give us an insight into the rate and effectiveness of the process at each stage and, therefore, an idea about how open innovation can improve the translation process.

We are all familiar with Alzheimer's disease. Not only is it a disease that causes significant morbidity and mortality, it is also one of the most costly. So, why haven't we cured it already? There are numerous reasons why this is a difficult problem to solve. The main problem being the lack of understanding of the disease itself, including potential drug targets. This leads to drug discovery being very risky and inefficient. For example, in the last few decades, extensive research has explored targeting amyloid plaques and neurofibrillary tangles as potential drug targets to treat Alzheimer's disease with little success. Furthermore, in the conventional drug development process, organizations work in isolation, creating an environment in which similar compounds are sometimes studied in parallel. So, how can we fix this problem? The answer lies in making the translation process between research and healthcare implementation more effective.

2015 Summer Scholar Profile: Ryan Louer

This summer, I will be working in Dr. Anthony Atala and Dr. James Yoo's lab under Drs. Myung Jae Jeon and Young Sik Choi studying ovarian cell therapies that will be able to produce natural levels of sex steroids that can be controlled by feedback mechanisms and, hopefully, produce viable oocytes. The importance of this research is providing effective therapies for hormone and egg replacement that do not have the potential harmful side effects, such as increased risk for heart disease and certain cancers, that current replacement methods pose. Cell-based therapies can be used in post-menopausal women, women who have had ovarian cancer, and women who have experienced damage to their ovaries from other sources.

Currently, we are characterizing a 3D collagen matrix and structure that closely mimics the natural environment within the ovary. My specific role in the project will be to test and define the importance of the ratio of granulosa cells to theca cells as well as find the optimum total number of cells in each follicle construct. I will be analyzing each ratio and follicle size for the ability to produce a physiologically normal level of estrogen and progesterone as well as assessing overall cell viability.

2015 Summer Scholar Profile: Jonah Simon

At the SRF Research Center, I am working on the Oncology team with Dr. Haroldo Silva. My project is to develop new high-throughput assays for quantifying activity of the Alternative Lengthening of Telomeres (ALT) pathway in human cells. Cancer cells must be able to proliferate without limit - something that normal cells can't do. Telomeres are repetitive noncoding DNA strands at the ends of eukaryotic (plants, animals, etc.) chromosomes. Every time a cell divides, telomeres shorten, protecting the genetic material from being damaged and limiting the proliferation of the cell. Some cells, such as stem cells and cancer cells, are able to lengthen their telomeres to be able to divide without limit. 85% of cancer cells use the enzyme telomerase to lengthen telomeres. The remainder maintain telomere length with ALT, a pathway based on homologous recombination (a mechanism used for DNA repair).

The current assays for ALT activity rely on characteristics of ALT cells: heterogeneous telomere length, the presence of ALT-associated PML bodies (APBs), and the presence of extrachromosomal circular C-strand telomeric DNA (C-Circles, or CCs). All of the current assays have problems, and none of them are high-throughput. One of the assays I'll be developing is a high-throughput version of the APB assay. Classically, this assay measures colocalization of PML protein with TRF2, a telomere binding protein (drug treatment can lower TRF2 expression, making the APB assay unreliable). I will bypass TRF2 and look for colocalization of PML with telomeric DNA directly. I'll accomplish this by using immunofluorescence to detect PML protein and FISH (fluorescent in situ hybridization) to detect telomeric DNA with a complementary fluorescent DNA probe.


Monday, June 22, 2015

Cryonics is a form of low-temperature preservation of tissue immediately following death, with the aim of preserving brain structure sufficiently well to allow future revival. Since the necessary technologies for revival can be envisaged in some detail, but remain far in the future, a large focus of the cryonics community is long-term risk and survival of cryopreservation organizations into at least the later decades of this century. A lot of ink has been spilled on this topic over the years, and this article covers some of the high points, such as politics, regulation, the necessity for growth in what is currently a small industry, and so forth:

Cryonics service providers offer their customers perpetual care. This care is meant to continue until medical technology has advanced to the point that their reanimation can be performed safely. While the most optimistic estimates are that reanimation may be possible in as little as fifty years, the time frame is normally considered to be hundreds of years. The poor quality of suspensions received by most persons, however, suggests that many will be reanimated only in the distant future, if at all. One of the greatest unknowns is whether these companies will be able to operate continuously over this period. An organizational failure of even a few months would terminate the experiment in medical time travel by causing irreparable damage to those in storage.

From an organizational standpoint, this offer of perpetual care is similar to that provided by the chantries established in England in the Middle Ages. Chantries were trusts established for the purpose of employing priests to sing a certain number of Masses during a stipulated period of time for the spiritual benefit of the deceased. The first perpetual Mass was established by royalty in the 1180s. Most institutions providing this service were suppressed in 1547 as part of the Reformation. Therefore, the 'perpetual' care lasted for less than four hundred years. This is also a reasonable estimate for the amount of time that a majority of those in cryonic suspension will require before any reanimation becomes possible. However, the chantries were established as part of the Roman Catholic Church or as institutions under its direction and control. During this period, the Roman Catholic Church was as powerful as a state and was considered by many to be the governing body of Europe. In contrast, cryonics organizations are very small businesses with extremely limited resources, subject to regulation by both State and Federal governments. The key question addressed here is whether and how such organizationally inferior institutions can achieve the longevity that the most powerful organization in Europe only barely achieved in earlier times.

Monday, June 22, 2015

Athletes at the top of their fields tend to live longer than the general population. The reasons for this are yet to be determined: for the most part human historical data can only show association, not causation. So it may be that more exercise is beneficial, or it may be that only the most robust people, who were going to live longer anyway, tend reach the heights of professional athletics, or it may be that the wealth, community, and access to medicine that comes with being a successful professional athlete are the critical influences:

To determine whether Olympic medallists live longer than the general population, we carried out a retrospective cohort study, with passive follow-up and conditional survival analysis to account for unidentified loss to follow-up. The study group consisted of 15,174 Olympic athletes from nine country groups (United States, Germany, Nordic countries, Russia, United Kingdom, France, Italy, Canada, and Australia and New Zealand) who won medals in the Olympic Games held in 1896-2010. Medallists were compared with matched cohorts in the general population (by country, age, sex, and year of birth).

More medallists than matched controls in the general population were alive 30 years after winning (relative conditional survival 1.08). Medallists lived an average of 2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13) than that of medallists in power sports (1.05). We conclude that Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory.

Tuesday, June 23, 2015

The trouble with cancer research is that all cancers are different; expensive and slow research results in only one therapy for one small group of cancer patients. Real progress would mean finding commonalities between many cancer types, or mechanisms essential to all cancer such as lengthening of telomeres. That is still a minority concern in the research community, but is growing thankfully in recent years. Nonetheless, since various types of cancer spring from specific mutations, it should be expected that with progress in biotechnology researchers will discover the basis for highly effective therapies for at least a few types of cancer:

Up to 90% of colorectal tumors contain inactivating mutations in a tumor suppressor gene called adenomatous polyposis coli (Apc). Although these mutations are thought to initiate colorectal cancer, it has not been clear whether Apc inactivation also plays a role in tumor growth and survival once cancer has already developed. This question has been challenging to address experimentally because attempts to restore function to lost or mutated genes in cancer cells often trigger excess gene activity, causing other problems in normal cells.

To overcome this challenge, researchers used a genetic technique to precisely and reversibly disrupt Apc activity in a novel mouse model of colorectal cancer. While the vast majority of existing animal models of colorectal cancer develop tumors primarily in the small intestine, the new animal model also developed tumors in the colon, similar to patients. Consistent with previous findings, Apc suppression in the animals activated the Wnt signaling pathway, which is known to control cell proliferation, migration, and survival. When Apc was reactivated, Wnt signaling returned to normal levels, tumor cells stopped proliferating, and intestinal cells recovered normal function. Tumors regressed and disappeared or reintegrated into normal tissue within 2 weeks, and there were no signs of cancer relapse over a 6-month follow-up period. Moreover, this approach was effective in treating mice with malignant colorectal cancer tumors containing Kras and p53 mutations, which are found in about half of colorectal tumors in humans.

Researchers continue to investigate why Apc is so effective at suppressing colon tumor growth, with the goal of one day mimicking this effect with drug treatments. "It is currently impractical to directly restore Apc function in patients with colorectal cancer, and past evidence suggests that completely blocking Wnt signaling would likely be severely toxic to normal intestinal cells. However, our findings suggest that small molecules aimed at modulating, but not blocking, the Wnt pathway might achieve similar effects to Apc reactivation. Further work will be critical to determine whether Wnt inhibition or similar approaches would provide long-term therapeutic value in the clinic."

Tuesday, June 23, 2015

Numerous scientists in the field of aging research declare their goal to be "healthy aging," which has always seemed to me to be a contradiction in terms. Aging is by definition a process of becoming more frail, more diseased, more damaged. There is a certain amount of politics in all of this, a result of all too many researchers still unwilling to talk in public about extending healthy life spans. Thus healthy aging and compression of morbidity become code phrases to allow these people to discuss the science of aging while pretending that efforts to prevent age-related disease will not extend life spans. Yet successful prevention of age-related disease must extend overall life span. Aging is an accumulation of tissue damage, and age-related disease is the result of that damage. Meaningful treatments for age-related disease will work by reducing levels of damage and thus extend life. An unwillingness to directly engage with this point is a part of the problem we face in finding sufficient funding and support for aging research to make rapid progress.

The current research topic inquires: "Should we treat aging as a disease?" Yet, in this inquiry, the question "Can aging be considered a disease?" is secondary, while the more primary question really must be "Is aging treatable?" Paradoxically, the answer given to the second question largely determines the answer to the first. The perceived unchangeable, and hence untreatable, nature of aging is the root cause for many subsequent rationalizations, even to the point of claiming the desirability of aging-derived suffering and death. This is a well recognized psychological phenomenon sometimes referred to as "apologism" or even "deathism," a ramification of the "sour grapes syndrome," vilifying something that we think we cannot attain, while accepting as "good" or "healthy" something that we believe is inevitable for us (such as degenerative aging). Yet, I argue that, historically, medical tradition has always recognized the morbid character of aging and endeavored to fight it. The rationalizations of aging as "natural," "justified," or "healthy" could never entirely prevail.

I argue that acknowledging the possibility of successful intervention into the aging process, in other words treating aging as a curable disease, has been a long and highly respected tradition of biomedical thought. It may just be observed that the proactive attitudes, aimed to ameliorate degenerative aging, tend to intensify thanks to the advancement of technological capabilities. Presently, the list of supporters of the cause of "curing aging" grows rapidly. The reason for this increase may be objective and tectonic. The world is rapidly aging, threatening grave consequences for the global society, in particular economy, which forces the society to seek solutions. On the other hand, biomedical science and technology are developing rapidly as well, increasing the feasibility of intervention and fostering our hope that a solution may be found.

Those may be "the push and the pull" or "the stick and the carrot" mighty forces that prompt more and more scientists and lay persons to move over to the camp of "treating aging as a disease," toward investing more and more time and effort for its amelioration or even cure, as soon as possible, for the benefit of all. Yet, the very idea of "treating aging as a disease," or some other title given to a morbid, debilitating and deadly condition, is by no means an intellectual novelty. It is a long established commonsensical intellectual tradition and a profound and ancient human desire. With the growing aging population and increasing technological capabilities, this idea is achieving an ever greater prominence. Eventually, the question whether aging should be considered "a treatable disease" may be reduced to technological capacity and semantics. While degenerative aging, that is the accumulation of structural damage, impairment of metabolic balance and functioning, may be seen as a disabling and deteriorative process that requires prevention and treatment, using advanced biomedical technology; the achievement of healthy longevity may be its cure.

Wednesday, June 24, 2015

Researchers have produced a prototype polymer device capable of performing one of the functions of a living neuron, the transmission of neurotransmitter chemicals. This is a small step towards a range of technologies important to very long-term goals in repair of the brain and extension of healthy life.

The brain is distinct from other organs in that we will never be able to outright replace more than small sections of it, which limits tissue engineering as an approach to repair in that portion of the central nervous system. Even when tissue engineers are capable of reproducing brain tissue, they will still have to restore existing cells and connections in situ in order to preserve the data of the mind. Eventually a collection of technologies will be needed to achieve this end, and many of them involve some sort of artificial replacement for living neurons. In the case of early applications in this space, such as bypasses for nerve and brain damage, these artificial neurons do not have to be fully functional or even as small as the real thing, but bear in mind that technologies such as the one demonstrated here are just the first step on a long pathway:

Neurons are isolated from each other and communicate with the help of chemical signals, commonly called neurotransmitters or signal substances. Inside a neuron, these chemical signals are converted to an electrical action potential, which travels along the axon of the neuron until it reaches the end. Here at the synapse, the electrical signal is converted to the release of chemical signals, which via diffusion can relay the signal to the next nerve cell. Scientists have now created an organic bioelectronic device that is capable of receiving chemical signals, which it can then relay to human cells.

"Our artificial neuron is made of conductive polymers and it functions like a human neuron. The sensing component of the artificial neuron senses a change in chemical signals in one dish, and translates this into an electrical signal. This electrical signal is next translated into the release of the neurotransmitter acetylcholine in a second dish, whose effect on living human cells can be monitored." The research team hope that their innovation will improve treatments for neurological disorders which currently rely on traditional electrical stimulation. The new technique makes it possible to stimulate neurons based on specific chemical signals received from different parts of the body. In the future, this may help physicians to bypass damaged nerve cells and restore neural function. "Next, we would like to miniaturize this device to enable implantation into the human body."

Wednesday, June 24, 2015

The Argus II is one of a variety of implanted electrode grid devices under development that supply a substitute for vision in the blind by stimulating the retina to produce phosphene patterns. Per this latest news, the device continues to progress much as expected in the clinical trial system. Most users in the latest small trial of several years benefited from the implant, and there were no device failures. Ultimately it might be expected that the research into retinal and optic nerve stimulation that produced the Argus systems will result in something closer to real vision. That, however, will require quite different and more sophisticated approaches than used at present, a process of development that has barely started, and for many types of blindness it may be overtaken by advances in retinal regeneration. It remains to be seen whether prosthetic technologies or regenerative medicine dominate in the years ahead for the alleviation of various types of damage that cause blindness:

Retinitis pigmentosa is an incurable disease that causes slow vision loss that eventually leads to blindness. The Argus II system was designed to help provide patients who have lost their sight due to the disease with some useful vision. Through the device, patients with retinitis pigmentosa are able to see patterns of light that the brain learns to interpret as an image. The system uses a miniature video camera stored in the patient's glasses to send visual information to a small computerized video processing unit which can be stored in a pocket. This computer turns the image to electronic signals that are sent wirelessly to an electronic device implanted on the retina, the layer of light-sensing cells lining the back of the eye.

The Argus II received Food and Drug Administration (FDA) approval as a Humanitarian Use Device (HUD) in 2013, which is an approval specifically for devices intended to benefit small populations and/or rare conditions. To further evaluate the safety, reliability and benefit of the device, a clinical trial of 30 people, aged 28 to 77, was conducted in the United States and Europe. All of the study participants had little or no light perception in both eyes. The researchers conducted visual function tests using both a computer screen and real-world conditions, including finding and touching a door and identifying and following a line on the ground. A Functional Low-vision Observer Rated Assessment (FLORA) was also performed by independent visual rehabilitation experts at the request of the FDA to assess the impact of the Argus II system on the subjects' everyday lives, including extensive interviews and tasks performed around the home.

The visual function results indicated that up to 89 percent of the subjects performed significantly better with the device. The FLORA found that among the subjects, 80 percent received benefit from the system when considering both functional vision and patient-reported quality of life, and no subjects were affected negatively. After one year, two-thirds of the subjects had not experienced device- or surgery-related serious adverse events. After three years, there were no device failures. Throughout the three years, 11 subjects experienced serious adverse events, most of which occurred soon after implantation and were successfully treated. One of these treatments, however, was to remove the device due to recurring erosion after the suture tab on the device became damaged.

Thursday, June 25, 2015

Understanding the storage model for human memory will enable a range of medical technologies relevant to repair and augmentation of the brain, but at present there is only a general consensus on the online of that model. Researchers believe that the data of memory is stored in the architecture of synapses, and here researchers provide more evidence that synapses are indeed the relevant location in mammals. This is perhaps of interest due to recent research in lower animals that seemed to rule out synaptic structures as the location of memory.

Our memories are as fleeting as the brain structures that store them, or so the theory goes. When the connections - called synapses - between neurons break, the memories they hold are thought to evaporate along with them. The idea seemed good, but has been hard to test. Now a team has taken on the challenge, studying a brain region called the hippocampus, which stores "episodic" memories. These are the memories of events or conversations that might be forgotten over time if the memories aren't used. The challenge to studying synapses in this region is that the hippocampus is so deep and the connections so densely packed that no microscope could easily monitor the synapses' longevity.

When mice experience a new episode or learn a new task that requires spatial navigation, the memory is stored for about a month in a structure at the center of the brain called the hippocampus (it is stored slightly longer in people). If mice have hippocampus-disrupting surgery within a month of forming a memory - a memory of meeting a new cage-mate or navigating a maze - that memory is lost. If the disruption occurs after more than a month, then the mouse still retains the memory of a new friend or location of food. That's because the memory had been relocated to a different region of the brain, the neocortex, and is no longer susceptible to disruption in the hippocampus.

In the past, scientists had monitored connections between neurons in the neocortex, nearer the brain's surface and therefore visible with little disruption to the brain. They watched not the connections themselves, but the bulbous projections called spines that form connections at their tips. Watching the spines come and go serves as a proxy for knowing when excitatory connections between neurons are created and broken. Those scientists found that about half of the spines in the neocortex were permanent and the rest turned over approximately every five to 15 days. "The interpretation was that about half the spines in the neocortex are long-term repositories for memories while others retain malleability for new memories or forgetting."

If the same line of thinking held true for the hippocampus as it did for the neocortex, spines in the hippocampus should turn over roughly every 30 days along with the memories they hold. Verifying that idea had been challenging, however, because the hippocampus is deeply buried in the brain and the spines in that region are so densely packed that multiple spines can appear to merge into one. The team overcame that problem with new techniques that allow stable imaging of a single neuron in a living mouse over long time periods, an optical needle, called a microendoscope, that provides high-resolution images of structures deep within the brain, and a mathematical model that took into account the limitations of the optical resolution and how that would affect the image datasets depicting the appearances and disappearances of spines. The researchers found that the region of the hippocampus that stores episodic memories contains spines that all turn over every three to six weeks - roughly the duration of episodic memory in mice.

Thursday, June 25, 2015

To what degree should we expect characteristic changes in behavior observed in the old to have a physical basis in neurodegeneration rather than being an outcome of living in our present cultures for a long time? If the neurodegeneration was prevented or repaired, what behavioral patterns would change, and why? Obviously researchers are a long way from providing defensible answers to those questions, but in this published research the authors provide evidence to suggest that behavioral flexibility is eroded in old age by a physical process, the destruction of a specific class of neuron:

Cholinergic interneurons are rare - they make up just one to two percent of the neurons in the striatum, a key part of the brain involved with higher-level decision-making. Scientists have suspected they play a role in behavioral flexibility, the ability to change strategy when the rules change, and researchers recently confirmed this with experiments. Previous studies tried to identify the role of cholinergic interneurons by recording brain wave activity during behavioral tasks. While that can strongly indicate specific neurons are correlated with a particular behavior, it is not definitive. In this study, researchers killed cholinergic interneurons with a toxin that directly targets them, and then observed how rats reacted to rule changes compared with normal rats with intact neurons. "Our experiments show direct causation, not correlation."

Rats with and without damaged neurons were given tasks for several weeks - they had to press either lever A or B to get a sugar pellet reward. During the first few days, Lever A always resulted in a reward. Both groups of rats had no problem learning the initial strategy to get the sugar pellet - press Lever A. But then, the rules of the game changed. A novel stimulus was introduced - a light flashed above the correct lever, which oscillated between Lever A and B. To get their sugar fix, the rats had to shift strategy and pay attention to this new information. While normal rats quickly responded to the light, rats with damaged neurons could not. The latter group continued to repeat the strategy they had already learned, and were disinclined to explore what the light meant.

"This indicates that cholinergic interneurons throughout the striatum play a common role, namely inhibiting old rules and encouraging exploration, but different regions of the striatum are activated depending on the situation and type of stimulus. Since cholinergic interneurons degenerate with age, this work may provide a clue for understanding the decline in mental flexibility that occurs with advancing age."

Friday, June 26, 2015

Researchers have found that the MEK inhibitor trametinib, used as a cancer treatment, modestly extends life in flies. This is of interest for researchers involved in mapping the relationships between metabolism and natural variations in longevity, but otherwise not all that significant in the grand scheme of things. The plasticity of life span in response to drug treatments that alter the operation of metabolism is much greater in short-lived creatures, and it should be expected that a small extension of life such as this one would map to next to nothing in humans, even assuming that the underlying mechanism of action is in fact shared. I believe that efforts to develop drug treatments to slow aging in humans based on this sort of result are doomed to lengthy and expensive failure, or at best result in very marginal therapies that will do no more than add a couple of years to life expectancy - something that can already be achieved through exercise or calorie restriction.

Adult fruit flies given a cancer drug live 12% longer than average, according to a study researching healthy ageing. Trametinib is used to treat skin cancer and was chosen for its ability to inhibit Ras signalling as part of the Ras-Erk-ETS cell pathway. The role of Ras has been well characterised in cancer but it is also known to affect the ageing process. Previously, the DNA of yeast was changed to reduce Ras activity, which extended lifespan, so the team wanted to explore inhibitors of this pathway in an animal. "Our aim is to understand the mechanisms of ageing and alter the processes that lead to loss of function and to disease. We studied this molecular pathway in flies because they are reasonably complex and yet age more quickly than mammals. We were able to extend their lifespan both genetically and by using a cancer drug to target the Ras pathway, which provides us with the first evidence for the anti-ageing potential of drugs developed to dampen this pathway."

Female fruit flies were given trametinib as an additive in their food. A small dose of 1.56 µM, which is approximately equivalent to a daily dose of the drug in a human cancer patients, increased the fruit flies' average life expectancy by 8%. With a higher dose of 15.6 µM, the flies lived 12% longer on average. To test the anti-ageing properties of the drug in later life, fruit flies over 30 days old that had almost all stopped laying eggs were given the same moderate dose of 15.6 µM, and still had an increased life expectancy of 4%. Flies exposed continuously to the drug from an earlier stage in life lived longer than those who began dosing later in life, possibly indicating a cumulative effect of the drug. "Identifying the importance of the Ras-Erk-ETS pathway in animal ageing is a significant step on the way to developing treatments that delay the onset of ageing. The pathway is the same in humans as it is in flies and, because the Ras protein plays a key role in cancer, many small molecule drugs already exist, some of which have been approved for clinical use. With support from pharma, we can refine these molecules over the next 10-20 years to develop anti-ageing treatments which don't have the adverse effects of cancer drugs."

Friday, June 26, 2015

Peter Thiel, who has invested millions into the SENS rejuvenation research programs over the past decade, has of late been talking much more in public on the topic of treating aging. Having wealth gives you a soapbox, and it is good that he is now using it to help the cause of treating aging as a medical condition. One of Thiel's recent public appearances was a discussion on death and religion in this context.

In the struggle to produce meaningful progress in rejuvenation research, the tipping point can come from either a very large amount of money, hundreds of millions at least, dedicated to something very similar to the SENS research programs, or from a widespread shift in the commonplace view of aging. At the large scale and over the long term medical research priorities reflect the common wisdom, and it is my view that public support is needed to bring in very large contributions to research. The wealthiest philanthropists and largest institutional funding bodies follow the crowd as a rule, they only rarely lead it. They presently give to cancer and stem cell research precisely because the average fellow in the street thinks that both of these are a good idea.

So it is very important that we reach a point at which research into treating degenerative aging is regarded as a sensible course of action, not something to be ridiculed and rejected. Over the past decade or two a great deal of work has gone into this goal on the part of a small community advocates and researchers. It is paying off; the culture of science and the media's output on aging research is a far cry from what it was ten years ago. When ever more authorities and talking heads are soberly discussing the prospects of extended healthy life and research into the medical control of aging, it is to be hoped that the public will follow. Inevitably religion is drawn in as a topic in these discussions once you start moving beyond the scientific community:

The Venn diagram showing the overlap of people who are familiar with both Peter Thiel and N.T. Wright is probably quite small. And I think it is indicative of a broader gap between those doing technology and those doing theology. It is a surprise that a large concert hall in San Francisco would be packed with techies eager to hear a priest and an investor talk about death and Christian faith, even if that investor is Peter Thiel.

Thiel has spoken elsewhere about the source of his optimism about stopping and even reversing aging. The idea is to do what we are doing in every other area of life: apply powerful computers and big data to unlock insights to which, before this era, we've never had access. Almost everyone I talk with about these ideas has the same reaction. First there is skepticism  - that can't really happen, right? Second, there is consideration  - well those Silicon Valley guys are weird, but if anyone has the brains and the money to do it, it's probably them. Finally comes reflection, which often has two parts - 1. I would like to live longer. 2. But I still feel a little uneasy about the whole idea.

The concept of indefinite life extension feels uncomfortable to people, thinks Thiel, because we have become acculturated to the idea that death, like taxes, is inevitable. But, he says, "it's not like one day you'll wake up and be offered a pill that makes you immortal." What will happen instead is a gradual and increasingly fast march of scientific discovery and progress. Scientists will discover a cure for Alzheimer's and will say, "Do you want that?" Of course our answer will be "Yes!" They will find a cure for cancer and say, "Do you want that?" And again, of course, our answer will be "Yes!" What seems foreign and frightening in the abstract will likely seem obvious and wonderful in the specific. "It seems," Thiel said, "that in every particular instance the only moral answer is to be in favor of it."

One of Wright's objections was to articulate a skepticism about whether the project of life extension really is all that good, either for the individual or for the world. "If [I] say, okay I'll live to be 150. I'll still be a sinner. I'll still be conflicted. I'll still have wrong emotions. Do I really want to go on having all that stuff that much longer? Will that be helpful to the world if I do?" This roused Thiel. "I really have to disagree with that last strikes me as very Epicurean in a way." For Peter Thiel, Epicureanism is akin to deep pessimism. It means basically giving up. One gets the sense he finds the philosophy not just disagreeable but offensive to his deepest entrepreneurial instincts and life experience. "We are setting our sights low," he argued, "if we say everyone is condemned to a life of death and suffering."


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