Fight Aging! Newsletter, December 9th 2013

FIGHT AGING! NEWSLETTER
December 9th 2013

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that 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!

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CONTENTS

  • 3:1 Matching for Next $15,000 Donated to SENS Research Before 12/31/2013
  • Differences Among the Naysayers
  • Jason Hope Partners With Fight Aging! to Match SENS Rejuvenation Research Donations This December
  • Methuselah Foundation Expands the Year End SENS Rejuvenation Research Donation Match
  • $1 Million New Organ Liver Prize Launched at the World Stem Cell Summit
  • Muscle Stem Cell Aging: "From Death, Lead Me to Immortality"
  • Latest Headlines from Fight Aging!
    • Linking RAGE Variations to Longevity
    • Creating Lung and Airway Cells From Stem Cells
    • Frailty is a Medical Condition
    • Generating Unlimited Numbers of Intestinal Stem Cells
    • Inhibiting IGF1 Signaling Reduces Misfolded Protein Aggregation in Aging
    • A Skeptic's Guide to Cryonics
    • An Opposition to Longevity That is Almost a Caricature of Itself
    • Responses to Daniel Callahan's Opposition to Human Longevity
    • Preserving Vision With Stem Cells in Retinal Degeneration
    • An Interview With Michael Rose in Cryonics Magazine

3:1 MATCHING FOR NEXT $15,000 DONATED TO SENS RESEARCH BEFORE 12/31/2013

As you'll see from this past week's news, Fight Aging! has been joined by generous offers from Jason Hope and the Methuselah Foundation to match the next $15,000 donated to the rejuvenation research programs of the SENS Research Foundation before the end of the year. Your donations will be matched 3:1 - so donate $50 and we will match it with $150! These funds will help to build the foundations of tomorrow's rejuvenation therapies, reversing the course of degenerative aging by repairing the molecular and cellular damage that causes it. Donate here:

http://sens.org/donate

This important research into rejuvenation biotechnologies is today entirely funded by philanthropic donations from people like you and I. Help us to make the future a better place, in which we live far longer, healthier lives, and do not suffer the pains and frailty of old age.

DIFFERENCES AMONG THE NAYSAYERS
https://www.fightaging.org/archives/2013/12/differences-among-the-naysayers.php

A fair number of people stand opposed to efforts to extend human life. A wide variety of reasons are given, including variants of the mistaken belief that life extension must mean some form of maintaining old people in increasing infirmity and pain for longer. In other words that improvements in human longevity will look just like those obtained from the past few decades of progress in medicine, expensive and ultimately futile attempts to patch over age-related conditions without doing much - or anything - to address their root causes. Daniel Callahan, who regular readers will recall has opposed efforts to extend longevity for some time, apparently holds this view.

On Dying After Your Time

Modern medicine is very good at keeping elderly people with chronic diseases expensively alive. At 83, I'm a good example. I'm on oxygen at night for emphysema, and three years ago I needed a seven-hour emergency heart operation to save my life. Just 10 percent of the population - mainly the elderly - consumes about 80 percent of health care expenditures, primarily on expensive chronic illnesses and end-of-life costs. Historically, the longer lives that medical advances have given us have run exactly parallel to the increase in chronic illness and the explosion in costs. Can we possibly afford to live even longer - much less radically longer?

This is not exactly correct. From an individual perspective the outcome of modern medicine is a longer life spent with less chronic illness. A rise in counts of age-related dysfunction is the result of many more people living longer - and this is a good thing. Those people enjoyed more years of active, healthy life before becoming sick. But the opening sentence is true: modern medicine is indeed good at keeping people alive when they would have died in past decades or centuries, and maintaining a heavily damaged system of any sort is an expensive proposition.

But that is today, not tomorrow. The root of Callahan's erroneous view of the future of medicine lies in thinking that future attempts to extend life, deliberately and by targeting the root causes of aging, will in any way be the same as past medical development. In the past, no efforts were made to address the underling causes of age-related degeneration, and all therapies ameliorated or patched over damage after it occurred, with treatment usually taking place in the very late stages of dysfunction. As an approach this is doomed to be both a failure and expensive. Yes, it provides considerable benefits in comparison to doing nothing, but it is a world removed from actually going after and removing the root causes of aging and age-related disease, such as by repairing the cellular and molecular damage that causes aging. This shift in focus from merely patching over to effectively addressing root causes is the greatest and most important change of our time in strategies for medical research and development. Comparing it to the importance of the advent of germ theory is not an exaggeration.

Callahan looks at what is and projects it into the future: the same fundamental failure that bedevils most prognosticators. You have to have a better grasp of what is taking place in the aging research community in order to see that the next generation of medical development to treat aging will be fundamentally different from what has come before. The scientists have been saying this for years, but all too many people are not listening.

Wesley J. Smith is another writer opposed to life extension - and indeed to pretty much all transhumanist projects aimed at overcoming the present limitations of the human condition. He critiqued the above piece by Callahan, pointing out a little of the double standard inherent when someone who is taking full advantage of modern medicine encourages others to die on a shorter time frame. It is probably the only thing Smith will scribe any time soon where I actually agree with some of what he is saying. This seemed a rare enough event to point it out.

Time to Prevent Elderly From Living Too Long?

Contrary to the transhumanist eschatology, Callahan doesn't believe that extending the length of lives will also mean extending their vitality. I tend to agree. But he doesn't exactly practice what he preaches. Callahan could have refused that expensive treatment. I don't say he should have, but no one forced him to spend all that (presumably) public money on care.

He does ask a valid question, I think, about the wisdom of pouring resources into radical life-extending research (at least public money). However he also seems to assert that the elderly be somehow prevented from living longer. What does that mean? Some kind of Logan's Run scenario? Callahan isn't that type. But he should have specified what he meant. As I read him, he seems to be proclaiming some kind of a moral duty of the elderly to die.

Or it could mean refusing efficacious medical care to the elderly that the younger would be able to obtain. In less genteel hands than Callahan's, it could mean something even more insidious.

There are factions who are quite willing to be up-front about plans to limit medical care for the elderly, though this is usually a dialog that takes place in the context of the huge mess that is government-funded provision of medicine. The most effective way to turn an economic benefit (longer lives, with more time spent in health) into an economic liability (destruction of currencies, economies, and rational behavior through inflation while promising future obligations that cannot be met) is to create a free commons of entitlements with a decoupling of services from costs. The inevitable results are rationing, poor service, research and development grinding to a halt as the incentives to improve vanish, and, ultimately, running out of other people's money to the point at which you see a collapse of the sort that ended the Soviet Union, or which is ongoing now in Venezuela.

Even aside from this, however, there are those who oppose even free and open efforts to extend healthy human life. Environmentalist movements are perhaps the most prevalent of these. All in all there are few topics beyond life extension that are so able to bring otherwise sensible, ordinary people to espouse hideous philosophies, such as demanding that the current toll of suffering and death, 100,000 lives lost to aging every day, while hundreds of millions suffer age-related pain and dysfunction, continue without any attempt made to improve the situation.

JASON HOPE PARTNERS WITH FIGHT AGING! TO MATCH SENS REJUVENATION RESEARCH DONATIONS THIS DECEMBER
https://www.fightaging.org/archives/2013/12/jason-hope-partners-with-fight-aging-to-match-sens-rejuvenation-research-donations-in-december.php

I am very pleased to announce that philanthropist and entrepreneur Jason Hope is joining in to expand the Fight Aging! 2013 year end matching fund for SENS rejuvenation research donations. Donations are tax deductible and help to expand important research aimed at extending our healthy life spans, reversing the downward slope of age-related disease and degeneration by repairing its root causes.

Through to the end of December 2013, Fight Aging! and Jason Hope will each match the next $15,000 donated to the SENS Research Foundation. Both Fight Aging! and Jason are each putting up $15,000 in matching funds, so every dollar donated will be matched by two dollars from this fund.

So jump on in and donate! Your gifts will help to fund ongoing cutting edge SENS research programs, undertaken in laboratories in the US and Europe, in which molecular biologists develop the means to repair the known forms of damage to cells and tissues that cause degenerative aging. This work is entirely funded by philanthropic donations, filling the gaps left where the mainstream medical research community is leaving important new work undone.

Jason Hope has previously provided $500,000 to the SENS Research Foundation, a gift that established the Cambridge SENS laboratory and founded a new research program that aims to break down advanced glycation end-products (AGEs) in human tissue. Age-related loss of elasticity and function in skin and other tissues is driven in part by a buildup of AGEs, largely of one type known as glucosepane. Glucosepane is a difficult chemical to work with and has been largely ignored by the mainstream research community despite the growing evidence of its importance to the course of degenerative aging. The SENS Research Foundation and Jason Hope are kick-starting this field of research, building the foundation that will allow many other laboratories to later step in and make effective AGE clearance treatments a reality, reversing this contribution to degenerative aging.

This is one of numerous research programs undertaken by the SENS Research Foundation, whose staff and allied network of researchers work to accelerate progress towards a future toolkit of rejuvenation therapies that actually, really work to reverse the course of aging. This is an era in which we can move beyond merely hoping and wishing when it comes to age-related frailty and disease. We can work to prevent it: the researchers are interested and ready, the research plans are in place, and all that is lacking is the funding for the proof of concept and foundation projects that will show the world what can be done.

Sufficient progress in the work of the SENS Research Foundation will allow many research groups around the world to step in, raise funds from more traditional, conservative sources, and carry forward the work of human rejuvenation to clinical trials and therapies. Everyone who helps this process through donations becomes a part of the broad community that is presently changing the entire face of aging research, shifting it from an investigative field to one that actually produces meaningful therapies and treatments: ways to prevent age-related disease and extend healthy life, and ways to rejuvenate the old, by repairing the low-level biological damage that makes them old.

Help us make a better, longer, healthier future for everyone! Donate!

METHUSELAH FOUNDATION EXPANDS THE YEAR END SENS REJUVENATION RESEARCH DONATION MATCH
https://www.fightaging.org/archives/2013/12/methuselah-foundation-expands-the-year-end-sens-rejuvenation-research-donation-match.php

I'm happy to say that Methuselah Foundation is joining the presently ongoing year-end matching of donations to the SENS Research Foundation. All donations are tax-deductible and will go towards expanding the SENS rejuvenation research programs presently taking place in laboratories around the world: building the foundation biotechnologies capable of repairing the accumulated low-level cellular and molecular damage that causes aging and age-related disease.

Methuselah Foundation joins philanthropist Jason Hope and Fight Aging! in this matching fund, each contributing $15,000 to match the next $15,000 contributed to SENS research before the end of 2013. Thus your donations will be matched 3:1!

  • Matching fund from Fight Aging!: $15,000
  • Matching fund from Jason Hope: $15,000
  • Matching fund from Methuselah Foundation: $15,000
  • Your donations, matched 3 to 1: $15,000
  • The total: $60,000

Methuselah Foundation is of course the precursor organization to the SENS Research Foundation, founded by David Gobel and Aubrey de Grey based on their shared interest in materially changing the course of aging research, to shift the scientific community from merely investigating aging to actually doing something about it. The Methuselah Foundation staff and volunteers contributed greatly to the shift in culture and goals that occurred within the aging research field over the past decade. Further, SENS research and fundraising first started under the Methuselah Foundation umbrella, alongside the Mprize for longevity science - a research prize that continues today to encourage researchers to demonstrate better and more effective means of extending healthy life through rejuvenation in laboratory mice.

Now that SENS has its own dedicated organization, the Methuselah Foundation focuses on accelerating goals in the tissue engineering of organs made from a patient's own cells: the Foundation funds breakthrough startups such as Organovo, and runs the New Organ initiative - a crowdfunding approach to generating a research prize to motivate faster development of replacement organs created to order. You'll be hearing more on that later this week, as there's a big launch presently ongoing at the World Stem Cell Summit.

There is only one roadblock standing between us and rapid progress towards the biotechnologies of rejuvenation outlined in the SENS research plans: that obstacle is money. The researchers are ready and interested, the research is planned and clear, the goals obvious - it just needs more funding than presently flows into this field. Aging research is the poor cousin of the medical life sciences, and rejuvenation research is the poor cousin of aging research: at the large scale research funding always goes towards the priorities of the past decade or two, not the forward-looking work that will form the basis for the future of medicine.

This is where you and I come in. We can see what needs to be done, and we can kickstart the necessary research projects through the SENS Research Foundation. Rarely is there such an obvious opportunity to do good in the world: to help eliminate the suffering, pain, and frailty of old age, and greatly extend healthy life.

So donate! Help make the world a better place for all of us.

$1 MILLION NEW ORGAN LIVER PRIZE LAUNCHED AT THE WORLD STEM CELL SUMMIT
https://www.fightaging.org/archives/2013/12/1-million-new-organ-liver-prize-launched-at-world-stem-cell-summit.php

The Methuselah Foundation has launched the New Organ Liver Prize as a part of the World Stem Cell Summit (WSWC) taking place this week. The aim of the prize is to spur one or more research groups to create functional tissue engineered livers from a patient's own cells and demonstrate their utility in animal studies by the end of 2018, five years from now.

Research prizes like this one work by through a combination of raising awareness, convincing more scientists to work on a particular problem, and motivating greater investment from both new and established funding sources in order to meet the prize goals. This is a long-proven method of invigorating and speeding fields in which progress is comparatively slow: there are many examples of successful research prizes both in recent years and past centuries.

The following missive from the Foundation arrived in the mail today to accompany the New Organ Liver Prize official launch:

This prize has been in the works for a long time, and we couldn't have done it without your enthusiastic support. Thank you! This launch is a victory for all of us, and we warmly invite you to share and celebrate the good news with everyone in your networks.

After much consideration with our scientific advisors, we decided to start with a liver-focused prize, and we intend to follow this up with a prize series that covers all the major solid organs, including the heart, kidney, and lungs. We're also working to mobilize other granting institutions to allocate additional funds in support of teams competing for the prize.

Here's what WSCS founder Bernie Siegel had to say: "Growing a whole, healthy organ is one of the ultimate goals of regenerative medicine. The world stem cell community enthusiastically supports the ambitious aim of the Methuselah Foundation in launching the New Organ Liver Prize and the mobilization of this competitive challenge for researchers to cure disease and alleviate human suffering through tissue engineering."

As you might notice, the Methuselah Foundation and New Organ websites are revamped for the occasion, and looking very modern. There is also an official press release (PDF):

The New Organ Liver Prize is the first in a series of whole organ challenges and awards designed to help solve the global organ shortage, which affects millions of people around the world. There are presently over 120,000 on the organ wait list in the U.S alone, many of whom will die before finding a compatible donor. Even those fortunate enough to receive an organ in time face ongoing medical difficulties, often for the rest of their lives.

New prospects for whole organ regeneration, engineering, and preservation offer potentially powerful solutions to this health crisis, but tissue engineering research is currently underfunded, receiving less than $500 million annually in the U.S. compared to $5 billion for cancer and $2.8 billion for HIV/ AIDS. Neither the NIH nor the NSF provide significant funding for whole organ tissue engineering, and the field also suffers from difficult regulatory hurdles as well as broader shortfalls in biotechnology investment for pre-clinical research.

New Organ has been endorsed by prominent doctors and scientists across the field of regenerative medicine, including Dr. Anthony Atala of Wake Forest, Dr. Stephen Badylak of the University of Pittsburgh, and the Founding Fellows of TERMIS (Tissue Engineering and Regenerative Medicine International Society).

"Regenerative medicine and tissue engineering are at the cusp of conquering the final frontier, the fabrication of vital organs to definitively solve the organ donor shortage," said Dr. Joseph Vacanti of Massachusetts General Hospital. "New Organ will help catalyze the efforts to solve the remaining problems to bring this life saving technology to all of the people who desperately need it."

Due to the complexity of defining strong competition criteria for each of the solid organs, including the heart, kidney, and lungs, this prize will focus exclusively on tissue engineering solutions that replace the liver. Ultimately, the Methuselah Foundation intends to develop a prize series that covers all of the major solid organs, and that spans multiple strategies, including organ regeneration, repair, replacement, and preservation. Through its New Organ Alliance, Methuselah also hopes to mobilize other granting institutions to allocate additional funds in support of teams competing for the prize.

The New Organ Liver Prize rules (PDF) are also worth looking over, especially if you've been following the development of this initiative over the past couple of years.

Type of Host:

Large mammal (specifically pig, cow, rabbit, dog, cat, sheep, baboon, or rhesus); excluding all rodents (rats, mice, etc.).

Duration:

A minimum of 90 days survivability.

Tissue:

Any bioengineered tissue solution is allowed.

Immunosuppression:

No immunosuppression is allowed if using animal cells; immunosuppression will only be allowed if using human cells.

Multiple Successes:

A minimum of 3 successful trials are required.

Success Rate:

A minimum of 3 out of 4 trials must be successful (75% success).

Functionality:

The animal must survive the duration of the 3-month survival trial and during the last month of the trial must exhibit specific liver functions and "lifestyle" functions.

Deadline:

The trials must be completed by December 31st, 2018.

Judging:

The team's trials will be evaluated by a technically-proficient and fully-independent judging committee.

Awards

The first team to meet all requirements will win the $1,000,000 award.

MUSCLE STEM CELL AGING: "FROM DEATH, LEAD ME TO IMMORTALITY"
https://www.fightaging.org/archives/2013/12/muscle-stem-cell-aging-from-death-lead-me-to-immortality.php

The crafting of histrionic titles for research papers is a small artistic sideline in the research community. They catch the eye, and it's only human to have a little fun from time to time while working with important topics. The important topic in this case is stem cell aging, a decline in stem cell activity that leads to increasingly frail and dysfunctional tissue due to reduced maintenance activities. Much of the work on this topic presently focuses on muscle tissue and the associated stem cells known as satellite cells: researchers will probably produce a usefully complete model of the important aspects of the epigenetics and other biochemistry of aging in satellite cells before similar investigations draw to a close for any other population of cells.

In recent years it has become apparent that much of the decline in satellite cell activities is a response to the environment of aged tissue. If you take old satellite cells and put them into young tissue they go back to work as though youthful. Similarly there have been demonstrations in which researchers restore some of the youthful activities of old stem cells by reverting one or more differences in chemical signaling noted between young and old environments.

I see the existence of this sort of work as a positive sign for the future. We need the researchers of the large and very well funded stem cell research community to become more interested in reversing age-related degeneration of stem cells. It is a big project, and will require a great deal of work. Fortunately most of the prospective therapies that can be created through the fruits of stem cell research are aimed at the treatment of age-related conditions. In order for these therapies to be effective, researchers are somewhat forced into understanding why stem cells decline in old tissue, and find ways to at least temporarily stop this from happening.

At the present time it is somewhat ambiguous as to whether damage to stem cells or signaling and epigenetic responses to broader cellular damage in tissue are the major cause of stem cell aging in all populations. But I don't expect that ambiguity to persist for too much longer, not if the funding keeps ramping up for regenerative medicine, tissue engineering, and other outgrowths of the stem cell field. Let us return to the histrionics, however:

'From Death, Lead Me to Immortality' - Mantra of Ageing Skeletal Muscle

The relationship between satellite stem cell function and muscle regeneration and repair in ageing has yet to be rigorously addressed in mammals. Initial in vitro studies of satellite cells from young and old animals suggested that there was intrinsic ageing of this stem-cell population, as aged cells generated far fewer progeny. The finding that regeneration mediated by aged satellite cells was highly effective when the cells were transplanted into young animals as whole-muscle grafts suggest reversible modifications of aged muscle stem cells, an interpretation supported by recent data showing that aged muscle stem cells, when exposed to a youthful systemic milieu by virtue of parabiotic pairings of aged and young mice, activate and repair muscle nearly as well as young satellite cells. These modifications may be associated with intrinsic epigenetic changes within the satellite stem cell population supported by our studies in myoblast cellular ageing demonstrating increased methylation of the myogenin gene [that] reduced the capacity to form myotubes which was reversed by addition of methyltransferase inhibitor 5-azacytidine.

The coordinated control of DNA methylation by methyltransferases and chromatin states by histone modifiers will be a fascinating avenue for further investigation and will particularly benefit from genome-wide examination in young and old stem cell populations. As technologies for genomic analysis and sequencing continually improve profiling potential correlation between stem cell function and epigenetic changes become increasingly feasible. As the mechanisms underlying age dependent stem cell decline are better understood that leads to a decline in muscle function, studying the effects of manipulating satellite cell function on skeletal muscle maintenance over a organismal lifespan and healthspan will be an attainable goal - 'from death, lead me to immortality'.

LATEST HEADLINES FROM FIGHT AGING!

LINKING RAGE VARIATIONS TO LONGEVITY
Monday, December 2, 2013
https://www.fightaging.org/archives/2013/12/linking-rage-variations-to-longevity.php

Advanced glycation end-products (AGEs) build up with age in our tissues, gumming together protein machinery and causing chronic inflammation and other bad behavior on the part of cells through the receptor for AGEs, or RAGE. Thus we should probably not be completely surprised to see associations between variations in RAGE and natural variations in longevity. This reinforces the need for AGE-breakers: treatments that can effectively break down and wash out AGEs, removing the harm that they do. Unfortunately few groups are working on this, despite the fact that there is apparently only one important type of AGE in human tissue.

Demographic and social changes in the last decades have resulted in improvements in health and longevity. The survival of elderly people has improved significantly and thus centenarians are becoming the fastest growing population group. Environmental, genetic, and accidental factors have influenced the human life span. Researchers have gained substantial evidence that advanced glycation end products may play an important role in the processes of physiological aging. The aim of the present study was to investigate any differences in the frequencies of -374T/A polymorphism [of the RAGE gene] in subjects aged 90 years or older and in middle-aged individuals.

We observed association between the A allele and genotype homozygous for this allele (AA) with a longer life expectancy in the male population. In particular, there was a prevalence of AA genotype and A allele in long-living subjects and a prevalence of the allele T in middle-aged subjects, indicating a possible protective role of the allele A to aging. In conclusion, our results support the hypothesis that longevity is the result of a good functioning of the immune system and a presumable hyper-expression of variants of anti-inflammatory genes of immunity. The differences in the genetic regulation of inflammatory processes may influence the presence of age-related disorders.

CREATING LUNG AND AIRWAY CELLS FROM STEM CELLS
Monday, December 2, 2013
https://www.fightaging.org/archives/2013/12/creating-lung-and-airway-cells-from-stem-cells.php

It was only a couple of years ago that researchers starting making progress in identifying and cataloging the stem cell populations in lung tissue. Last year researchers mapped out some of the cellular path of development for lungs in embryos. Here they are building on that to grow lung cells from embryonic and induced pluripotent stem cells, which opens the doors to the next stage of lung tissue engineering development.

"Researchers have had relative success in turning human stem cells into heart cells, pancreatic beta cells, intestinal cells, liver cells, and nerve cells, raising all sorts of possibilities for regenerative medicine. Now, we are finally able to make lung and airway cells. This is important because lung transplants have a particularly poor prognosis. Although any clinical application is still many years away, we can begin thinking about making autologous lung transplants - that is, transplants that use a patient's own skin cells to generate functional lung tissue."

The research builds on [the] 2011 discovery of a set of chemical factors that can turn human embryonic stem (ES) cells or human induced pluripotent stem (iPS) cells into anterior foregut endoderm - precursors of lung and airway cells. In the current study, [researchers] found new factors that can complete the transformation of human ES or iPS cells into functional lung epithelial cells (cells that cover the lung surface). The resultant cells were found to express markers of at least six types of lung and airway epithelial cells, particularly markers of type 2 alveolar epithelial cells. Type 2 cells are important because they produce surfactant, a substance critical to maintain the lung alveoli, where gas exchange takes place; they also participate in repair of the lung after injury and damage.

FRAILTY IS A MEDICAL CONDITION
Tuesday, December 3, 2013
https://www.fightaging.org/archives/2013/12/frailty-is-a-medical-condition.php

Somewhere lurking in the roots of medical progress is the urge to declare portions of degenerative aging to be medical conditions. At one point all degeneration was accepted as an inevitable part of the inevitable process of aging - a matter of "it is what it is." Then dementia was declared a condition, and then heart disease, and so on through the presently accepted set of age-related diseases. These have been split off from aging and declared to be treatable.

The division between named diseases of aging and aging is artificial, nothing more than taxonomy. Eventually there will be no aging in the popular eye, just a very long laundry list of medical conditions. This is the way it should be, because aging is just a very long laundry list of medical conditions, caused by known forms of underlying damage that are open to treatment and repair. The more that this is accepted, the more support there will be for research and development of rejuvenation treatments.

As a medical resident 30 years ago, Ava Kaufman remembers puzzling over some of the elderly patients who came to the primary-care practice at George Washington University Hospital. They weren't really ill, at least not with any identifiable diseases. But they weren't well, either. They were thin and weak. They had no energy. They tired easily. Their walking speed was agonizingly slow. "We couldn't put our finger on a specific diagnosis or problem,'' Kaufman says. "We didn't have a word for it then.''

Today we do. It's called frailty. There have always been frail people, but only in recent years has the term "frailty" become a medical diagnosis, defined by specific symptoms and increasingly focused on by those who deal with the medical issues of the elderly. Clinicians now are looking at ways to prevent or delay frailty, sometimes even reverse it. "Frailty is not an age, it's a condition," says Kaufman, a Bethesda internist and geriatrician. "We know it when we see it, and it's always been with us."

GENERATING UNLIMITED NUMBERS OF INTESTINAL STEM CELLS
Tuesday, December 3, 2013
https://www.fightaging.org/archives/2013/12/generating-unlimited-numbers-of-intestinal-stem-cells.php

Researchers have been making more progress of late in identifying and using stem cells that support intestinal tissue. A few years ago a research group managed to grow small amounts of intestinal tissue, and other similar demonstrations have been achieved since then. Here is an example of present work that should make it much easier to generate the type of cells needed for further research and development:

[Researchers] have shown that they can grow unlimited quantities of intestinal stem cells, then stimulate them to develop into nearly pure populations of different types of mature intestinal cells. Using these cells, scientists could develop and test new drugs to treat diseases such as ulcerative colitis.

The small intestine, like most other body tissues, has a small store of immature adult stem cells that can differentiate into more mature, specialized cell types. Until now, there has been no good way to grow large numbers of these stem cells, because they only remain immature while in contact with a type of supportive cells called Paneth cells.

In a new study [the] researchers found a way to replace Paneth cells with two small molecules that maintain stem cells and promote their proliferation. Stem cells grown in a lab dish containing these molecules can stay immature indefinitely; by adding other molecules, including inhibitors and activators, the researchers can control what types of cells they eventually become.

If scientists could obtain large quantities of intestinal epithelial stem cells, they could be used to help treat gastrointestinal disorders that damage the epithelial layer. Recent studies in animals have shown that intestinal stem cells delivered to the gut can attach to ulcers and help regenerate healthy tissue, offering a potential new way to treat ulcerative colitis.

INHIBITING IGF1 SIGNALING REDUCES MISFOLDED PROTEIN AGGREGATION IN AGING
Wednesday, December 4, 2013
https://www.fightaging.org/archives/2013/12/inhibiting-igf1-signaling-reduces-misfolded-protein-aggregation-in-aging.php

The signaling pathways associated with insulin-like growth factor 1 (IGF-1) are one of the better studied parts of the intersection between metabolism and aging. So we might expect some marginal treatments to emerge here over the next decade, based on altering metabolism to produce modest beneficial effects by slowing the rate at which some forms of age-related damage occur. In this case the slowed damage involves build up of misfolded proteins associated with neurodegenerative conditions:

TyrNovo's novel and unique compound, named NT219, selectively inhibits the process of aging in order to protect the brain from neurodegenerative diseases, without affecting lifespan. Human neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases share two key features: they stem from toxic protein aggregation and emerge late in life.

[Researchers] discovered, working with worms, that reducing the activity of the signaling mechanism conveyed through insulin and the growth hormone IGF1, a major aging regulating pathway, constituted a defense against the aggregation of the Aβ protein which is mechanistically-linked with Alzheimer's disease. Later, [they] found that the inhibition of this signaling route also protected Alzheimer's-model mice from behavioral impairments and pathological phenomena typical to the disease. In these studies, the path was reduced through genetic manipulation, a method not applicable in humans.

[TyrNovo researchers] discovered a new set of compounds that inhibit the activity of the IGF1 signaling cascade in a unique and efficient mechanism, primarily for cancer treatment, and defined NT219 as the leading compound for further development.

A SKEPTIC'S GUIDE TO CRYONICS
Wednesday, December 4, 2013
https://www.fightaging.org/archives/2013/12/a-skeptics-guide-to-cryonics.php

Cryonics is a small industry that provides low-temperature storage (via vitrification, not freezing) of the body and brain on death. The mind is just structure, and that structure can be preserved for a future in which advanced medical engineering can restore a vitrified mind to life. This will most likely involve a mature nanorobotics industry and the ability to accurately and efficiently manipulate low-level cell structures: things that are a long way out but not beyond reach or impossible.

Sadly the propositions of cryonics are sufficiently forward-looking that most people reject it out of hand without even looking at the wealth of supporting evidence or considering the odds in an unbiased fashion. We live in a world in which it is economically feasible to preserve the mind of near everyone who dies: there could be a massive cryonics industry, with cryonics as the default end of life choice. Yet the status quo is to do nothing, and people evaporate into oblivion. Once the structure of the mind is destroyed there is definitely no coming back from that. If our culture were more rational the choice of cremation or the grave would be the one that is looked at askance, mocked, or rejected out of hand.

Can a case for cryonics be made on skeptical grounds? If we'd have to believe self-identified skeptics this is not only unlikely but cryonics, in fact, is a "logical" target for skeptical scrutiny. The most obvious approach for a skeptic is to demand "proof" for cryonics. Upon closer inspection, this apparently reasonable demand is rather odd. Let's start with a non-controversial definition of cryonics: cryonics is a form of critical care medicine that stabilizes critically ill patients at ultra-low temperatures to allow the patient to benefit from future advances in medicine. Now, what could this demand for "proof" consist of? Does the cryonics advocate need to provide proof that future developments in medicine will indeed be capable of treating the patient? How could such a proof be even remotely possible? The most scientifically responsible answer would be to say "I don't know." And this answer reveals something important about cryonics. The decision to make cryonics arrangements is a form of decision making under uncertainty. Asking for "proof" for such a decision makes little sense.

Why has cryonics traditionally gotten such a poor reception by people who see themselves as "skeptics?" I suspect that some of it has to do with the fact that cryonics is traditionally associated with (religious) concepts such as immortality, very optimistic projections about the accelerating growth of science and technology, the technical feasibility of specific repair technologies (such as molecular nanotechnology), or mind uploading. But none of these ideas is an intrinsic part of the idea of cryonics. In its most basic form cryonics is just the recognition that what might be beyond the scope of contemporary medicine may be treatable in the future. No specific timeframe or technology is implied, or necessary. There are a lot of things that people in liquid nitrogen don't have, but one thing they do have is time.

AN OPPOSITION TO LONGEVITY THAT IS ALMOST A CARICATURE OF ITSELF
Thursday, December 5, 2013
https://www.fightaging.org/archives/2013/12/an-opposition-to-longevity-that-is-almost-a-caricature-of-itself.php

The quoted material below is a condensed example of sort of thing we see from many opponents who flail away at the prospects for extending health life. They say that it couldn't possibly work; that even it if did no-one would be better for living longer; that we're all selfish for trying; that the advocates and researchers are all working on it for the wrong reasons; and so on and so forth. Really it says a lot more about the author than the topic at hand. It must take an effort of will to so blind oneself to the essentially positive nature of medical research that aims to remove pain, suffering, and death, of seeking longer life for the pleasure of living, so as to do more and achieve more, and to see the next day dawn because you are curious.

It is instructive to read most of the opposition to longevity science while replacing the objective at hand with, say, therapies for heart disease, or improvements in organ transplantation. All modern advances in medicine of the past few decades are intended to push back pain, suffering, and death. All change the nature of the human condition - and all can be argued against used the same terms as are brought out for efforts to treat, slow, and reverse aging itself. Yet none of these opponents try to argue against heart disease treatments. It shows just how hollow their positions are.

Medical development to extend healthy, vigorous life spans is completely and absolutely beneficial: it will make life better, extending all that is good while suppressing the worst physical aspects of the human condition. The work is being accomplished by people who are drawn to this field of research for the ability to make a meaningful difference: to cure, to build new ways to improve health and longevity, to stop the terrible ongoing flood of pain and death caused by degenerative aging. That some people can so twist reality as to present medical progress as some sort of selfish pursuit towards self-destruction is a tribute to misapplied ingenuity.

While any detailed examination of the science invoked will promptly dispel the idea that such an ambitious extension to our lives is likely at all, and even a moment's reflection will generate a host of reasons as to why it may be even less desirable that it is likely, it is still a compelling narrative. Who really wants to die - when they could just keep living? Of course mortality is necessary, and the species needs it - but not for me. Surely my survival, my ever-accumulating wisdom, will be a noble exception, a major benefit to society? We could all advance such self-serving arguments, but if we really take the idea seriously, we have to see it as an attempt to impose stasis on the inevitable flux that is reality.

Given that death is inevitable, that mortality and finitude is blindingly and undeniably the frame in which we live our lives - why engage in these grand acts of self-delusion? Of course, some life extension may be possible, but death will not be denied, and, even if delayed a little en route by healthy living and medical advances, is coming for us all soon enough. I can only see a single psychological motive underpinning the longevity movement, and this is the same reason it sells newspapers and fascinates so many of us. This motive is our absolute and total fear and dread. The more we have suppressed death, the more we may fail to express our anxiety - but it has gone nowhere. I would contest that underneath the cheery hopes of living for centuries is a screeching, desperate flailing panic at the knowledge of our own, personal, death. The fact of death is, alas, still a fact; and longevity and immortality are as useless as the cheap trinkets of 'heaven' and post-death-life. What little we can do, surely, consists of the staring down, and confronting of the truth of death. This choice promises no escape, but at least offers us the chance to live a life where death's long shadow does not taint every thought via poorly-repressed anxiety.

RESPONSES TO DANIEL CALLAHAN'S OPPOSITION TO HUMAN LONGEVITY
Thursday, December 5, 2013
https://www.fightaging.org/archives/2013/12/responses-to-daniel-callahans-opposition-to-human-longevity.php

Daniel Callahan is among those who oppose efforts to extend human life. He holds mistaken views on the outcome of longevity-enhancing therapies, thinking that they will extend the period of frailty and illness rather than extend healthy, vigorous life. In this he is determinedly ignoring what scientists in the field have been saying - loudly in many cases - for many years. Unfortunately he is not alone in this selective deafness: the average fellow on the street also thinks that extending life through medical science means being older for longer, not being younger for longer. This is a major hurdle still to be overcome on the way to gaining more support for medical research and development aimed at slowing or reversing aging.

Here are a few responses from interested researchers to Callahan's latest article, including some involved in the Longevity Dividend initiative:

Mainstream aging research neither promises radical immortality nor seeks to keep old people sick longer. Aging is a driving factor in the most prevalent and costly chronic diseases. Research indicates that interventions slowing aging delay the onset of these diseases. Therefore, they extend not only life span but also health span, the disease-free and functional period of life.

Fundamentally, the goals of aging research are not dissimilar from efforts to prevent or treat Alzheimer's or other chronic diseases in that they both seek to improve quality of life in the elderly. The difference is that interventions in aging may prevent not just one but a range of debilitating diseases simultaneously.

Mr. Callahan's concern about older people crowding out younger people for jobs is also unfounded. We saw warnings of this kind before when women began to join the work force. A result was that women added nearly $3 trillion to the economy, and businesses owned by women employ nearly 16 percent of the work force.

If health at any age is highly valued, then a healthier older population is worth its weight in gold. Aging science is likely to be the next revolution in public health; it should be embraced, not feared. Anti-aging research is not, as Daniel Callahan apparently believes, about prolonging the wheelchair-and-walker phase of life but about preserving youthful health and vigor so that there will be far fewer of the elderly in poor health.

I'm always amazed at the number of people who vigorously support the search for better prevention and treatment of heart disease, cancer and Alzheimer's but who find moral difficulties in the search for better prevention and treatment of those plus a host of other maladies, all simultaneously. That is what anti-aging research is about.

PRESERVING VISION WITH STEM CELLS IN RETINAL DEGENERATION
Friday, December 6, 2013
https://www.fightaging.org/archives/2013/12/preserving-vision-with-stem-cells-in-retinal-degeneration.php

An example of recent work on stem cell treatments for forms of age-related degenerative blindness:

The advances in stem cell biology hold a great potential to treat retinal degeneration. Importantly, specific cell types can be generated efficiently with small molecules and maintained stably over numerous passages. Here, we investigated whether neural stem cell (NSC) derived from human embryonic stem cells (hESC) by small molecules can preserve vision following grafting into the Royal College Surgeon (RCS) rats; a model for retinal degeneration.

A cell suspension containing NSCs or NSCs labeled with green fluorescent protein (GFP) was injected into the subretinal space or the vitreous cavity of RCS rats at postnatal day 22; animals injected with cell-carry medium and those left untreated were used as controls.

NSCs offered significant preservation of both photoreceptors and visual function. Functionally, NSC treated eyes had significantly better visual acuity and lower luminance threshold than controls. Morphologically, photoreceptors and retinal connections were well preserved. There was an increase in expression of cillary neurotrophic factor (CNTF) in Müller cells in the graft-protected retina.

This study reveals that NSCs derived from hESC by small molecules can survive and preserve vision for long term following subretinal transplantation in the RCS rats. These cells migrate extensively in the subretinal space and inner retina; there is no evidence of tumor formation or unwanted changes after grafting into the eyes.

The NSCs derived from hESC by small molecules can be generated efficiently and provide an unlimited supply of cells for the treatment of some forms of human outer retinal degenerative diseases. The capacity of NSCs migrating into inner retina offers a potential as a vehicle to delivery drugs/factors to treat inner retinal disorders.

AN INTERVIEW WITH MICHAEL ROSE IN CRYONICS MAGAZINE
Friday, December 6, 2013
https://www.fightaging.org/archives/2013/12/an-interview-with-michael-rose-in-cryonics-magazine.php

Researcher Michael Rose has interesting views on aging and longevity that diverge from much of the rest of the present research community. He is possibly best known for his work showing a late-life mortality plateau in flies - if you define aging as a rising risk of death per unit time, then there is very clearly a point at which aging stops in that species. Mortality is still high and the flies still die, but for a while they are what Rose terms "immortal," a term he adopts to mean no further rise in mortality rate. So far the data is either ambiguous or in opposition to the existence of a mortality plateau in humans, however.

My work on the evolution of aging in response to changes in the first age of reproduction has been emulated with mice by Nagai, Lin, and Sabour (1995, Growth Dev Aging), who showed that you get the same qualitative results with rodents as with flies. This and other experiments manipulating the timing of reproduction in other species show that Hamilton's 1966 Forces of Natural Selection are the fundamental controls on aging. As for the full range of experiments in the Rose and Mueller labs on the evolution and cessation of aging, no one else has come up with such a complete range of experiments to test the hypothesis that Hamiltonian theory explains the onset, rate, and cessation of aging.

Hamilton's forces start to fall after the start of reproduction, which is when aging starts. But Hamilton's forces eventually stop falling at late adult ages. If aging only occurs during or a bit after these forces are falling, then aging must eventually stop too. This means that mortality rates, fertility, and virility should all eventually reach plateaus at which they change only gradually. That is what we have found in our lab data with fruit flies.

SENS and most other thinking about aging is dominated by the hypothesis originally due to Aristotle that aging is produced by some type of physiological process, whether that process involves damage or a death program. In Hamiltonian thinking, aging is the de-tuning of adaptation during the first part of adulthood. As such, we see aging as a problem as complicated as that of evolutionary adaptation itself. Thus we expect that aging is due to many problematic nucleotide frequencies, distributed genome-wide, which in turn generate pleiotropic and epistatic effects of great complexity throughout the biology of aging organisms.

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