Fight Aging! Newsletter, November 25th 2013

November 25th 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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  • Fight Aging! Provides $15,000 Matching Fund For Rejuvenation Research Donations
  • Biochemistry (Moscow), Home of Programmed Aging
  • Recent Research Into the Epigenetics of Aging
  • Cryonics Videos From Alcor Life Extension Foundation
  • Greater Advocacy for the Longevity Dividend
  • Latest Headlines from Fight Aging!
    • Steven Austad on Cryonics
    • A Review of the Use of Viruses to Attack Cancer
    • Growing Small-Scale Kidney Structures From Stem Cells
    • Gene Therapy For Heart Failure
    • Methionine Restriction Works to Extend Longevity In Yeast Too
    • Muscle Mitohormesis Promotes Longevity
    • The Aging Lung Reviewed
    • Superior Proteome Stability in Long-Lived Clams
    • Acarbose Extends Life in Mice
    • Factors Correlating With Survival to Age 90 From Age 70


As you might be aware, the SENS Research Foundation is the leading light when it comes to funding the most meaningful research into human rejuvenation. The Foundation staff have the plan, the allied network of researchers and laboratories, and are gathering the necessary funds from philanthropists and a grassroots community of supporters. I strongly encourage you to read the Foundation's research and annual reports to see for yourself that it is the real deal. This is an age of biotechnology in which we no longer have to hope and handwave when it comes to reversing degenerative aging: the way forward to producing future therapies capable of rejuvenating the old and preventing age-related disease is very clear indeed.

Rejuvenation Therapies: All It Takes Is Money

Researchers stand ready and interested. All it will take to get the job done is money and a couple of decades of hard work by hundreds of scientists. But mainly the money: funding is ever the limiting factor, not the availability of researchers or the need for a plan.

This year the SENS Research Foundation has set a year end fundraising target of $100,000 from donors and the community by the end of December. The funds will be used to expand Foundation research and other programs. This is the time of year when people traditionally turn to making charitable donations, but I have to say that this is definitely a stretch goal for our community: the past year has seen numerous funded projects, several in just the last few months alone. Supporters have given tens of thousands of dollars to help fund advocacy and research projects that advance the state of the art.

Fight Aging! Puts Up $15,000 In Matching Funds

Stretch goal or not, I am going to do my part to help make this happen. Through sheer and unlikely happenstance the princely sum of $15,000 recently landed in my lap, out of the blue, and with no strings attached. Sometimes fortune smiles upon us. I am putting this forward as a matching fund for donations to the SENS Research Foundation:

Fight Aging! will match, 1:1, the next $15,000 donated to the SENS Research Foundation before the end of December 2013.

So take the step and donate to help fund the best and the most promising rejuvenation research. I'll match your donation.

Why Fund Rejuvenation Research Now?

Now is the time! For one the research itself is tantalizingly close to applicable results: a few years of sustained funding is all that separates us from laboratory demonstrations of a way to replace age-damaged mitochondrial DNA or a way to remove the greatest contributing factor to loss of skin elasticity, in both cases opening the path to eliminating those contributions to aging.

Secondly it is very self-evident that funding given to research now will snowball and attract much more research funding in the future. In fact this has already happened: our comparatively small community has bootstrapped its way into generating somewhere in the vicinity of $25-30 million of funding for our brand of longevity science and advocacy since the turn of the century. Barely a tenth of that came from the grassroots and the early supporters, but that tenth is by far the most important portion, and those who make it the most important donors. Without the grassroots, without the community and its support and its advocacy, the larger donations never happen: wealth follows the crowds in science funding, and the crowds follow the early adopters.

Yet this is still the ground floor. These are still the early days, in which small acts can make a vast difference to the future of human health and longevity. Most people don't yet know or care about what can be achieved. New billion dollar research communities and vast medical development industries still lie ahead. In 2025 we will look back at 2010-2015 as being a point of takeoff, another early part of the upward curve in which ever more people funded new and revolutionary longevity science instead of giving to the old per-disease foundations, and in which the old institutions began to pay more attention to research into aging: its slowing, and its reversal.

There are precious few times in life when you can stand at a juncture with enough foresight to know that you can swing the odds meaningfully. Most such opportunities slip past us, realized too late. But if you are here now, reading this post, then you are almost certainly one of the folk who knows enough to make a difference.

So Help Me Out Here: Help Us All Live Far Longer and Healthier Lives

Donate! Help the SENS Research Foundation undertake that next research project, make that next investment in a new lab, move that next step towards realizing the means to rejuvenate the old and prevent age-related pain, frailty, and disease.


One of the most important divides in the aging research community today is that between the view of aging as a result of the stochastic accumulation of cellular and molecular damage and the view of aging as resulting from an evolved genetic program. The former is the majority position, but the programmed aging camp is fairly vocal these days. Personally, I fall into the aging as damage camp based on my understanding of the literature. The programmed aging view is certainly interesting, but I think its proponents have a steeper hill to climb when it comes to proving their theories.

Why is this an important difference of opinions? It is important because the types of therapy that work well in the world where aging is damage are not so good in a world in which aging is programmed, and vice versa. We are already in a situation in which all too much of the funding for longevity science goes towards research programs that are only capable of producing expensive, marginal outcomes: drug development aimed at slowing aging that attracts funding because it can be sold as a slight evolution of the present methodology of medical research and development. That it can't possibly lead to rejuvenation or indeed any significant result soon doesn't matter: people get funded, and researchers for better or worse chase the funding that can be obtained, not the funding that might be obtained in a better world.

(To my eye it is up to advocates to change the funding landscape: researchers don't tend to try anywhere near aggressively enough. It requires someone from outside the system of patronage and relationships to come in and kick people until they start doing what they should and what is sensible).

But back to programmed aging. This situation, a focus on drug development aimed at slowing aging, or patching over the consequences of damage by altering specific protein levels to resemble the youthful amounts, will only get worse if the programmed aging camp successfully increases their influence in funding circles. To the programmed aging viewpoint the entire problem is that protein levels are wrong, and aging can be reversed by reverting them - reprogramming the machinery. From the aging as damage viewpoint this is the cart before the horse, an approach doomed to expensive failure because it doesn't fix the underlying cause of aging, which is to say the damage itself.

The way to short circuit this slowly ongoing cultural and scientific debate is for a proposed methodology of rejuvenation through damage repair - such as SENS - to be implemented in the laboratory. The cost of this is very low, on a par with the cost of developing a single drug in the present regulatory environment. If SENS works, which is to say significantly extends the life and restores the health of old animals, then we can probably throw programmed aging theories out of the window in short order. Theory is theory, but proof is proof.

The SENS research community is not so many years away from being able to do just this for some aspects of the SENS program. The more money we can raise for their research, the faster it goes.

The Russian biogerontology community is very much ground zero for new work on programmed aging, and with language barriers lowering and increased scientific collaboration between regions a lot more of their publications come to my attention. The open access journal Biochemistry (Moscow) regularly runs issues packed with papers on aging as an evolved genetic program. This is the case again in Volume 78(9), and as always it makes for interesting reading even while disagreeing.

Arguments Against Non-programmed Aging Theories

Until recently, non-programmed theories of biological aging were popular because of the widespread perception that the evolution process could not support the development and retention of programmed aging in mammals. However, newer evolutionary mechanics theories including group selection, kin selection, and evolvability theory support mammal programmed aging, and multiple programmed aging theories have been published based on the new mechanics.

Some proponents of non-programmed aging still contend that their non-programmed theories are superior despite the new mechanics concepts. However, as summarized here, programmed theories provide a vastly better fit to empirical evidence and do not suffer from multiple implausible assumptions that are required by non-programmed theories. This issue is important because programmed theories suggest very different mechanisms for the aging process and therefore different mechanisms behind highly age-related diseases and conditions such as cancer, heart disease, and stroke.

Phenoptosis as Genetically Determined Aging Influenced by Signals from the Environment

Aging is a complex and not well understood process. Two opposite concepts try to explain its causes and mechanisms - programmed aging and aging of "wear and tear" (stochastic aging). To date, much evidence has been obtained that contradicts the theories of aging as being due to accumulation of various damages. For example, creation of adequate conditions for the functioning of the organism's components (appropriate microenvironment, humoral background, etc.) has been shown to cause partial or complete reversibility of signs of its aging.

Programmed aging and death of an organism can be termed phenoptosis by analogy to the term apoptosis for programmed cell death. The necessity of this phenomenon [has] been justified by the need for population renewal according to ecological and evolutionary requirements. Species-specific lifespan, age-dependent changes in expression pattern of genes, etc. are compatible with the concept of phenoptosis.

However, the intraspecific rate of aging was shown to vary over of a wide range depending on living conditions. This means that the "aging program" is not set rigidly; it sensitively adjusts an individual to the specific realities of its habitat. Moreover, there are indications that in rather severe conditions of natural habitat the aging program can be completely cancelled, as the need for it disappears because of the raised mortality from external causes (high extrinsic mortality), providing fast turnover of the population.

Post-Reproductive Life Span and Demographic Stability

Recent field studies suggest that it is common in nature for animals to outlive their reproductive viability. Post-reproductive life span has been observed in a broad range of vertebrate and invertebrate species. But post-reproductive life span poses a paradox for traditional theories of life history evolution. The commonly cited explanation is the "grandmother hypothesis", which applies only to higher, social mammals.

We propose that post-reproductive life span evolves to stabilize predator-prey population dynamics, avoiding local extinctions. In the absence of senescence, juveniles would be the most susceptible age class. If juveniles are the first to disappear when predation pressure is high, this amplifies the population's risk of extinction. A class of older, senescent individuals can help shield the juveniles from predation, stabilizing demographics and avoiding extinction. If, in addition, the life history is arranged so that the older individuals are no longer fertile, the stabilizing effect is further enhanced.

Advanced Glycation of Cellular Proteins as a Possible Basic Component of the "Master Biological Clock"

During the last decade, evidence has been accumulating supporting the hypothesis that aging is genetically programmed and, therefore, precisely timed. This hypothesis poses a question: what is the mechanism of the biological clock that controls aging? Measuring the level of the advanced glycation end products (AGE) is one of the possible principles underlying the functioning of the biological clock. Protein glycation is an irreversible, non-enzymatic, and relatively slow process. Moreover, many types of cells have receptors that can measure AGE level. We propose the existence of a protein that has a lifespan comparable to that of the whole organism. Interaction of the advanced glycation end product generated from this protein with a specific AGE receptor might initiate apoptosis in a vitally important non-regenerating tissue that produces a primary juvenile hormone. This could result in the age-dependent decrease in the level of this hormone leading to aging of the organism.


A fair-sized fraction of present aging research relates to epigenetic changes that occur with aging. Epigenetics is the study of gene expression, the process by which proteins are produced from genetic blueprints, and the many different ways in which gene expression changes in response to health and environmental factors. The machineries of life are controlled by dynamic alterations in circulating levels of specific proteins, and these ongoing changes in metabolism feed back into one another to produce a responsive, self-regulating system of enormous complexity.

The cellular and molecular damage of aging causes characteristic changes in gene expression, and these can be picked out from the more general set of random - or perhaps just less well-understood - changes in gene expression that occur over time. Researchers are primarily cataloging these changes, but some are also using increasingly efficient tools to restore the gene expression of specific genes to youthful levels in animal studies. To my eyes this will be the basis for therapies to treat age-related conditions that will prove to be more effective than the present state of the art. Nonetheless, it isn't the direct road to rejuvenation, as changing gene expression that is altered in response to damage doesn't deal with the underlying issue, which is the existence of that damage.

(As has been pointed out in comments on past posts, there isn't a clear line to be drawn between manipulating protein levels in a way that is less helpful versus doing so in a way that actually does address underlying damage. If you can alter levels of a protein so as to spur greater clearance of undesired misfolded protein aggregates, for example, then you are in fact creating some degree of rejuvenation. You are removing damage. But if, as is usually the case, changing gene expression to restore youthful operation of a system does nothing to repair underlying damage to that system, then it cannot be the best path forward. Consider, for example, restoring stem cell activity through changed gene expression: this most likely comes with a raised risk of cancer, as stem cell decline with aging is most likely an evolved response to increasing levels of damage in stem cells. Turn off that response and cancer rates should increase, even through great benefits to health through increased tissue maintenance can be realized).

A handful of recently published research results are illustrative of the sort of work being done at the intersection of epigenetics and aging.

Inflammatory skin damage in mice blocked by bleach solution, study finds

[Researchers] tested the effect of daily, 30-minute baths in [dilute] bleach solution on laboratory mice with radiation dermatitis. They found that the animals bathed in the bleach solution experienced less severe skin damage and better healing and hair regrowth than animals bathed in water. They then turned their attention to old - but healthy - laboratory mice.

"Multiple research studies have linked increased NF-kB activity with aging. We found that if we blocked NF-kB activity in elderly laboratory mice by bathing them in the bleach solution, the animals' skin began to look younger. It went from old and fragile to thicker, with increased cell proliferation." The effect diminished soon after the dilute-bleach baths were stopped, indicating that regular exposure is necessary to maintain skin thickness. "We found that the bleach solution oxidizes and inhibits an activator necessary for NF-kB to enter the nucleus, essentially blocking NF-kB's effect."

Aging Impacts Epigenome in Human Skeletal Muscle

The results came from the first genome-wide DNA methylation study in disease-free individuals. DNA methylation involves the addition of a methyl group to the DNA and is involved in a particular layer of epigenetic regulation and genome maintenance. In this study researchers compared DNA methylation in samples of skeletal muscle taken from healthy young (18 - 27 years of age) and older (68 - 89 years of age) males. [Researchers] looked at more than 480,000 sites throughout the genome. "We identified a suite of epigenetic markers that completely separated the younger from the older individuals - there was a change in the epigenetic fingerprint."

Scientists identified about six-thousand sites throughout the genome that were differentially methylated with age and that some of those sites are associated with genes that regulate activity at the neuromuscular junction which connects the nervous system to our muscles.

Aging erodes genetic control, but it's flexible

In yeast at least, the aging process appears to reduce an organism's ability to silence certain genes that need to be silenced. Now [researchers] who study the biology of aging have shown that the loss of genetic control occurs in fruit flies as well. In several newly published experiments they show that gene silencing via chromatin in fruit flies declines with age.

They also showed that administering life span extending measures to the flies, such as switching them to a lower calorie diet or increasing expression of the protein Sir2, restores the observed loss of gene silencing due to age.

Orexin restores aging-related brown adipose tissue dysfunction in male mice

The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with iBAT morphological abnormalities and thermogenic dysfunction. In-vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphological characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy.

Our results suggest a role for orexin-signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass was accelerated in mice in which orexin-producing neurons were ablated. Conversely, orexin injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.


Cryonics is the science and industry of preserving the physical structure of the mind on death, indefinitely preventing its decay through low-temperature storage. At some point future technology will be capable of restoring a preserved individual to active life - and given what we know about aging and the pace of development in biotechnology, it is likely that this will be long past the point at which degenerative aging is cured, and complete control over growth, disease, and regeneration is achieved. Those are arguably easier challenges than that of restoring a vitrified brain into a new body. The difficulty is irrelevant if you can wait for decades or centuries, of course. Time is on the side of the cryopreserved provided that the institutions of cryonics continue for the long term.

The Alcor Life Extension Foundation is one of the small number of cryonics providers, a long-term venture dating back four decades to the early days in which cryonics moved from overambitious amateur venture to a more professional medical undertaking. If you take a look at the Alcor News blog, you'll find a link to a recent Nova video segment that didn't run on air, but can be viewed online:


Since 1972, a company called Alcor has been preserving legally dead people at very low temperatures. The hope is that, in the future, scientists will be able to revive these "patients," giving them a chance for eternal life. It may sound like the stuff of science fiction, but host David Pogue met with Alcor president and CEO Max More to tour the facility and learn about the field of "cryonics."

NARRATOR: Near the hot desert just outside of Phoenix, Arizona is a company called Alcor. Despite the high temperature outside, within, over 100 human bodies are being preserved at very low temperatures. Host David Pogue met with the president and CEO Max More to learn about the field of cryonics.

DAVID POGUE: So who's in this gallery here?

MAX MORE: These are some of our patients. We call them patients because we don't regard them as dead people. The idea is that what we call death today is somewhat of an arbitrary line. Really it's today's doctors giving up and saying, "There's nothing more I can do for this person and I'm letting them go." What we're doing is we're saying, "Let's not quit there. Let's give the future a chance to bring these patients back."

As it turns out Alcor has a YouTube channel these days. I shouldn't be at all surprised - any organization of any size either has a channel or should have a channel, with YouTube or a similar service. It's an obvious step when it comes to outreach and education, provided your budget rises to at least the modest level required to produce informative videos of a suitable quality. So if you take a look you'll find a brace of videos from the Alcor 40 conference held last year, as well as a series of FAQ videos to explain cryonics and its role in medicine.


The Longevity Dividend is an advocacy and education initiative that aims to gather sufficient public and political support to reshape the flow of public funds into aging science: to explicitly aim to slow aging and extend healthy life, and to greatly increase government funding for that goal via the National Institutes of Health. The initiative has been around for some years, but of late the level of organization and public advocacy has stepped up a few notches. This, the continuing success of the SENS Research Foundation in gathering support and allies in the scientific community, and Google's Calico operation are, I think, all signs of the times. Past years of persistent advocacy have succeeded in waking up some portions of the community, and the results are now emerging. This is the entry into the next cycle of development, in which there is a lot more funding and interest for medical research that might potentially extend healthy human life spans.

Investments in aging biology research will pay longevity dividend, scientists say

Finding a way to slow the biological processes of aging will do more to extend the period of healthy life in humans than attacking individual diseases alone, according to some of the nation's top gerontologists writing in the latest issue of Public Policy & Aging Report (PP&AR), titled "The Longevity Dividend: Geroscience Meets Geropolitics." The authors showcase work in the emerging interdisciplinary field of geroscience, which is based on the knowledge that aging itself is the major risk factor for most chronic diseases prevalent in the older population. "In recent years, researchers studying the biological underpinnings of the aging process have made impressive progress in understanding the genetics, biology, and physiology of aging," said GSA Executive Director and CEO James Appleby, RPh, MPH. "With adequate research support, we could be in reach of a breakthrough similar to those in public health in the 19th century and medicine in the 20th."

While researcher S. Jay Olshansky's article in the PDF linked below is much more ambitious in terms of goals and possibilities than I recall being the case for his public position in the past - there is a table in there that includes the word "immortality," for example - this is still not open support for SENS and rejuvenation of the old through repair therapies. It is support for slowing aging, which implicitly means support for the present slow road in aging research, the drug development and metabolic manipulation that is unlikely to result in great gains, and which will absorb a great deal of time and money in the course of going pretty much nowhere.

Still, a starting point is a starting point. When the Longevity Dividend folk set to work in order to dispel public misconceptions relating to overpopulation and increased infirmity in longer lives - both absolutely unfounded fears - then all efforts to extend life benefit. A rising tide raises all boats, and it is in everyone's interest to inform the public that yes, life extension in fact means health extension, and population will generally grow only slowly as human life spans become much longer.

The Longevity Dividend: Geroscience Meets Geropolitics (PDF)

The case for the longevity dividend is extremely compelling and, in theory, should be easy to make to funders, public-health professionals, and the general public. Here is the line of reasoning:

  • Treating diseases worked well in the past to extend healthy life, but aging has emerged as the primary risk factor for the most common fatal and disabling diseases.

  • The longer individuals live, the greater the influence of aging on disease expression.

  • Aging science offers medicine and public health a new and potentially far more effective weapon for preventing disease, extending healthy life, and avoiding the infirmities associated with old age.

  • Failing to take this new approach could leave people who reach older ages in the future even more vulnerable to rising disability than they are now.

  • Aging science represents a new paradigm of public health that has the potential to yield more effective methods of delaying most fatal and disabling diseases, extending healthy life, and reducing the prevalence of infirmities more commonly experienced at older ages
  • Although people who benefit from advances in aging science will probably live longer, the extension of healthy life is the primary goal. In addition, reductions in the infirmities of old age and increased economic value to individuals and societies would accrue from the extension of healthy life.

    It is only a matter of time before aging science acquires the same level of prestige and confidence that medicine and public health now enjoy, and when that time comes, a new era in human health will emerge. An abundance of formidable obstacles are standing in the way, including strongly held views of how to proceed, a history of association with dubious aging interventions, and misconceptions about the goals in mind and the impact of success on population growth and the environment. Once the air clears and aging science is translated into effective and safe interventions that can be measured and documented to extend our healthy years, the 21st century will bear witness to one of the most important new developments in the history of medicine.

    The article by Dan Perry is also worth reading:

    Like the rough beast of the famous poem by W. B. Yeats, a scientific consensus that aging might be slowed to avert chronic diseases in older people is slouching toward serious consideration in public policy.

    Richard Miller addressed a scientific audience a few years ago with an only slightly tongue-in-cheek assessment of why biogerontology has failed to be embraced as a panacea for age-related diseases and disability among the older population. Miller assessed the obstacles to finding a cure for aging as 85 percent political and 15 percent scientific. Among the political obstacles Miller noted:

  • Aging is viewed (incorrectly) as unalterable.

  • Drugs that actually slow aging cannot be tested in time to show a profit within the CEO's lifetime; whereas drugs purported to slow aging are highly profitable even though they don't work.

  • A politician who wants to "conquer cancer" is a hero.

  • A politician who wants to "slow aging" is a nut-case.
  • Regardless of which of Miller's hurdles are most daunting, the fact remains that federal funding of biomedical research continues to pursue cures and better treatments for specific diseases, especially for those with vocal constituencies. Recent developments, however, including congressional interest and creation of the trans-NIH Geroscience Interest Group (GSIG), are setting the stage for a determined push for increased federal support for age-modifying research with clinical potential.

    SENS and rejuvenation research is still not a part of this funding picture. Those involved are generally much more conservative, or at least feel the need to appear so in public. I think it will take more years of steady growth in funding and support for SENS, and the emergence of one or two important technology demonstrations in rejuvenation resulting from ongoing SENS Research Foundation projects for it to start to feature in discussions of large-scale funding and goals. All funding at this level is political, the public funding much more so of course, and change is slow.


    Monday, November 18, 2013

    Scientist Steven Austad is well known in the field of aging research. For the past few years he has penned a column for a Texas paper - the sort of public engagement that I'd like to see more researchers undertake on a regular basis. Here he writes on the topic of cryonics, which is something else I'd like to see more researchers do on a regular basis, even if they clearly need to better investigate the topic first:

    Cryonics is the idea - or more precisely, the hope - that by freezing your body after death, future scientists will be able to bring that body back to life. Why future scientists would want to do this isn't exactly clear. Maybe there will be no more pressing problems in the future than bringing dead people back to life. Anyway, assuming they wanted to for some reason, the real hope is not that only your body would be brought back to life, but that you would be brought back to life. Something like awakening after surgery.

    Cryonics embodies a rather touching faith in scientific progress. Or maybe it embodies only an exceptional fear of death. In either case, it raises some interesting philosophical questions. What would it take for that newly re-animated body to still be "you?" With a little tweaking of existing technology, we could create a genetically identical copy of you as we've already done in mice, dogs, and a number of other species, by cloning a cell from your current body. But that wouldn't really be you, because it wouldn't have your memories or experiences.

    Memories are the key. Thus, the frozen head. As long as your brain still contains your memories, your re-animated head could be thought of as you. As for the rest of your body, any science sophisticated enough to bring your head back to life should no doubt be able to give you the body you want. I'll have to think about whose body I'd like.

    Besides, keeping only your head saves money. Cryonics is not cheap. Prices I've seen range from about $30,000 for a budget deal to several hundred thousand, not including the currently unknown cost of re-animating you and putting a body to that head. Long lines of freezers packed with bodies like so many popsicles uses a lot of expensive liquid nitrogen and takes up a lot of space, for who knows how many years? Freezers full of hat box-size containers are comparatively economical and good for the profit margin.

    There do seem to be some formidable scientific barriers though, even if you assume that re-growing a body is feasible. For one thing, no one has brought something even as simple as a single cell back from being dead, not that I'm sure how much effort has been put into doing so. Another issue is that our memories are thought to be a product of the number and strength of very delicate electrical connections among our billions of brain cells. Memory can be seriously disrupted by something as simple as a blow to the head. So preserving those things through a complete cessation of all brain electrical activity and the inevitable postmortem damage to brain cells seems more than a little far-fetched. Also, if you died of a stroke or dementia, sorry, you're out of luck. Those critical memory centers were destroyed even before you died.

    Whatever your opinion of cryonics, to my mind the head thing needs rethinking. The important thing obviously is preservation of the brain. So why not freeze just the brain rather than the whole head? If science proceeds to the point where they can re-grow a complete body, surely it will be able to give me a better head.

    Cryonics is a process of low-temperature vitrification rather than freezing these days, which is an important distinction to make. Frozen tissue is damaged by ice crystal formation, vitrified tissue is not to any significant degree. Vitrified cells and even organs in recent years have in fact been restored from this form of low-temperature storage. There is also good evidence to show that the fine structures of neurons that store the data of memory are well preserved by vitrification.

    Most people who undertake cryonics are of modest means, and cryonics providers are not run as for-profit companies at this time. The cost of cryonics is generally managed through a life insurance policy. With enough forethought a tiny monthly payment puts you in good shape for a future cryopreservation - and it is certainly the case that organizing your own end of life choices requires planning ahead. Last minute decisions tend to run poorly.

    Why preserve the whole head? Because trying to do otherwise is more likely to result in damage to the brain and will raise costs by requiring more skill and training for paramedical staff. The cryopreservation process has to happen fairly rapidly and involves perfusion of cryoprotectant chemicals. Adding an additional major operation to that process, while at the same time removing a layer of protection from the brain, doesn't sound like a great plan to me.

    Monday, November 18, 2013

    Targeted killing of cancer cells is the future of cancer treatment, an approach that results in better outcomes and fewer side-effects. Numerous different mechanisms to target and destroy specific types of cell have been developed in recent years, and one of these involves the use of natural or engineered viruses that preferentially attack cancer cells:

    Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity.

    With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy.

    OVs provide a number of potential advantages as cancer vaccines over conventional therapies. First, OVs are tumor-selective, thus in situ cancer vaccines, providing higher cancer specificity and better safety margin. Second, immunogenic/inflammatory types of cell death, including recently characterized "immunogenic cell death" (ICD) of cancer and stromal cells induced by OVs provides a natural repertoire of tumor-associated antigens (TAAs) in conjunction with danger signals to elicit anti-tumor immunity.

    Tuesday, November 19, 2013

    An example of early stage progress towards building new kidney tissue to replace aged or diseased kidneys, or for use in bioartificial kidney devices:

    For the first time, [researchers] have generated three-dimensional kidney structures from human stem cells, opening new avenues for studying the development and diseases of the kidneys and to the discovery of new drugs that target human kidney cells. Scientists had created precursors of kidney cells using stem cells as recently as this past summer, but [this] team was the first to coax human stem cells into forming three-dimensional cellular structures similar to those found in our kidneys.

    [The] findings demonstrate for the first time that pluripotent stem cells (PSCs)-cells capable of differentiating into the many cells and tissue types that make up the body-can made to develop into cells similar to those found in the ureteric bud, an early developmental structure of the kidneys, and then be further differentiated into three-dimensional structures in organ cultures. UB cells form the early stages of the human urinary and reproductive organs during development and later develop into a conduit for urine drainage from the kidneys. The scientists accomplished this with both human embryonic stem cells and induced pluripotent stem cells (iPSCs), human cells from the skin that have been reprogrammed into their pluripotent state.

    Tuesday, November 19, 2013

    Using gene therapy to alter levels of specific proteins in a targeted fashion is an intermediary advance in medicine for age-related conditions. Practical applications of this technology should provide an improvement over what came before, but at the same time they don't treat the underlying issue, which is the accumulation of cellular and molecular damage that causes aging and the diseases of aging. At some point the medical community must change its focus from patching over the problem to addressing its root causes.

    [Researchers] have successfully tested a powerful gene therapy, delivered directly into the heart, to reverse heart failure in large animal models. The new research study findings [are] the final study phase before human clinical trials can begin testing SUMO-1 gene therapy. SUMO-1 is a gene that is "missing in action" in heart failure patients.

    [In an earlier trial] a gene known as SERCA2 is delivered via an inert virus - a modified virus without infectious particles. SERCA2 is a gene that produces an enzyme critical to the proper pumping of calcium out of cells. In heart failure, SERCA2 is dysfunctional, forcing the heart to work harder and in the process, to grow larger. The virus carrying SERCA2 is delivered through the coronary arteries into the heart during a cardiac catheterization procedure. Studies show only a one-time gene therapy dose is needed to restore healthy SERCA2a gene production of its beneficial enzyme.

    But previous research [discovered] SERCA2 is not the only enzyme that is missing in action in heart failure. [The] SUMO-1 gene is also decreased in failing human hearts. But SUMO-1 regulates SERCA2a's activity, suggesting that it can enhance the function of SERCA2a without altering its levels. A follow-up study in a mouse model of heart failure demonstrated that SUMO-1 gene therapy substantially improved cardiac function. This new study tested delivery of SUMO-1 gene therapy alone, SERCA2 gene therapy alone, and a combination of SUMO-1 and SERCA2.

    In large animal models of heart failure, the researchers found that gene therapy delivery of high dose SUMO-1 alone, as well as SUMO-1 and SERCA2 together, result in stronger heart contractions, better blood flow, and reduced heart volumes, compared to just SERCA2 gene therapy alone.

    Wednesday, November 20, 2013

    Calorie restriction extends life and improves health in nearly every species tested to date. Sensing of levels of methionine, an essential amino acid, appears to be one of the controlling mechanisms involved in the shift of metabolism into a state that ensures greater longevity. Reduction in dietary methionine without reducing calories has been show to extend life in rats and mice, for example. Here researchers demonstrate that it can do so in yeast as well:

    It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media.

    Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms.

    Wednesday, November 20, 2013

    A hormetic process is one in which a little damage spurs damage repair mechanisms into an extended effort, leading to a net positive gain. A number of means of extending life in laboratory animals involve hormesis, and many of those involve mitochondria, the power plants of the cell that emit damaging reactive molecules as a side-effect of their operation. Dial up the output of those reactive molecules and the rest of the cell will react with a greater level of housekeeping operations. Something like this is thought to be one of the mechanisms linking exercise to greater health and longevity, for example.

    Mitochondrial dysfunction is usually associated with aging. To systematically characterize the compensatory stress signaling cascades triggered in response to muscle mitochondrial perturbation, we analyzed a Drosophila model of muscle mitochondrial injury. We find that mild muscle mitochondrial distress preserves mitochondrial function, impedes the age-dependent deterioration of muscle function and architecture, and prolongs lifespan.

    Strikingly, this effect is mediated by at least two prolongevity compensatory signaling modules: one involving a muscle-restricted redox-dependent induction of genes that regulate the mitochondrial unfolded protein response (UPRmt) and another involving the transcriptional induction of the Drosophila ortholog of insulin-like growth factor-binding protein 7, which systemically antagonizes insulin signaling and facilitates mitophagy. Given that several secreted IGF-binding proteins (IGFBPs) exist in mammals, our work raises the possibility that muscle mitochondrial injury in humans may similarly result in the secretion of IGFBPs, with important ramifications for diseases associated with aberrant insulin signaling.

    Thursday, November 21, 2013

    This open access review paper on the characteristic changes of aging that occur in lung tissue and function illustrates the importance of immune system decline as a component of the frailty of aging. It impacts all of the major organs. Reversing the structural issues that cause much of the decline in immune response would be an early quick win in the development of human rejuvenation, and the necessary therapies - such as targeted destruction of unwanted immune cells, and replacement with cells grown from the patient's stem cells - could be implemented independently of all of the other necessary line items in a rejuvenation toolkit, and implemented within the next couple of years with no great advances in the state of the art:

    There are many age-associated changes in the respiratory and pulmonary immune system. These changes include decreases in the volume of the thoracic cavity, reduced lung volumes, and alterations in the muscles that aid respiration. Muscle function on a cellular level in the aging population is less efficient. The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy. Clearance of particles from the lung through the mucociliary elevator is decreased and associated with ciliary dysfunction.

    Many complex changes in immunity with aging contribute to increased susceptibility to infections including a less robust immune response from both the innate and adaptive immune systems. Considering all of these age-related changes to the lungs, pulmonary disease has significant consequences for the aging population. Chronic lower respiratory tract disease is the third leading cause of death in people aged 65 years and older.

    With a large and growing aging population, it is critical to understand how the body changes with age and how this impacts the entire respiratory system. Understanding the aging process in the lung is necessary in order to provide optimal care to our aging population. This review focuses on the nonpathologic aging process in the lung, including structural changes, changes in muscle function, and pulmonary immunologic function, with special consideration of obstructive lung disease in the elderly.

    Thursday, November 21, 2013

    The proteome is the set of all proteins expressed by an organism; stability in expression levels over time indicates fewer changes in the operation of metabolism, which might also indicate slower aging. Looking at proteomic stability as a hallmark of longevity seems a little tautological to me, but nonetheless now that the tools exist to cheaply and accurately measure genome-wide gene expression levels you will see researchers talking about this data and how it relates to degenerative aging. Long-lived naked mole rats, for example, appear to have a more stable proteome across their lifespans, and here we see that this is also the case for the longest-lived clam species:

    Bivalve mollusks have several unique traits, including some species with exceptionally long lives, others with very short lives, and the ability to determine the age of any individual from growth rings in the shell. Exceptionally long-lived species are seldom studied yet have the potential to be particularly informative with respect to senescence-resistance mechanisms. To this end, we employed a range of marine bivalve mollusk species, with lifespans ranging from under a decade to over 500 years, in a comparative study to investigate the hypothesis that long life requires superior proteome stability. This experimental system provides a unique opportunity to study closely related organisms with vastly disparate longevities, including the longest lived animal, Arctica islandica.

    Specifically, we investigated relative ability to protect protein structure and function, both basally and under various stressors in our range of species. We found a consistent relationship between species longevity, resistance to protein unfolding, and maintenance of endogenous enzyme (creatine kinase) activity. Remarkably, our longest-lived species, Arctica islandica (maximum longevity of more than 500 years), had no increase in global proteome unfolding in response to several stressors. Additionally, the global proteome of shorter-lived species exhibited less resistance to temperature-induced protein aggregation than longer-lived species.

    A reporter assay, in which the same protein's aggregation properties was assessed in lysates from each study species, suggests that some endogenous feature in the cells of long-lived species, perhaps small molecular chaperones, was at least partially responsible for their enhanced proteome stability. This study reinforces the relationship between proteostasis and longevity through assessment of unfolding, function, and aggregation in species ranging in longevity from less than a decade to more than five centuries.

    Friday, November 22, 2013

    Researchers have demonstrated that acarbose, a drug used to treat type 2 diabetes, extends life in mice. This should probably be taken as speculative until more studies are run, as another treatment for type 2 diabetes, metformin, has erratic results on life span in rodent studies. Like metformin, the mechanism of action for arcabose involves influencing glucose metabolism, though in a completely different way.

    Studies of this nature take place because the high costs of regulation in medical development, along with the reluctance of regulators to approve anything new these days, make it more cost-effective to find marginal new uses for existing drugs than to go out and develop new therapies or new classes of therapies. It is unfortunate that so much research time is diverted into channels that cannot result in radical breakthroughs or great advances.

    A drug commonly used to treat type 2 diabetes increases the median lifespan of male mice by 22 percent. The effects of the drug known as acarbose were smaller in female mice, producing only a 5 percent increase in lifespan. The study also found that the effect on maximum lifespan was similar in male and female mice, increasing longevity by 11 percent and 9 percent, respectively. "The new results on acarbose support the idea that drugs may someday be developed to prevent many diseases while also slowing the aging process itself."

    Acarbose [is] believed to work by slowing the digestion of starches, which prevent rapid increases in blood sugar levels after meals. Most of the mice in the study die of some form of cancer. Authors say the longer lifespan of the acarbose-treated mice suggests that the drug may, through unknown pathways, help to prevent cancer as aging proceeds. [Because] acarbose is known to be safe for long-term human use, it may be possible for clinical researchers to evaluate its effects on aging and age-related diseases, both in people who take the drug to treat their diabetes, and in healthy volunteers. "Further studies in mice may shed light how the cellular and physiological connections between acarbose and control of glucose levels may influence the pace of aging."

    Friday, November 22, 2013

    I noticed this study today which reinforces the well-known correlation between wealth and longevity, but more strongly reinforces the point that people age at different rates. If you have developed more pronounced age-related disease or disability at 70, then your odds of reaching 90 are not so good in comparison to your more healthy peers. Aging is damage, and age-related disease and degeneration is the visible manifestation of that damage. Insofar as we have control over the pace of aging, that is a matter of good lifestyle choices: exercise, calorie restriction, good use of preventative medical resources, and so forth. There is also the matter of supporting research so as to improve the capabilities of the medical technologies available in your old age - a factor much more important than the others when it comes to determining your expected length of life.

    To identify factors associated with survival to the age of 90 years old in 70+ elderly people [we examined data from] 75 randomly selected administrative communities in Gironde and Dordogne (France) [containing members of the] PAQUID prospective cohort on brain and functional ageing. A sub-sample of 2,578 community dwellers aged 70 years and over at baseline in 1988 [were followed] over 20 years. Data on socio-material environments, lifestyle, health, perceived health, and family background were collected at home every 2-3 years over 20 years, with a prospective update of vital status. Participants were compared according to their survival status (subjects who reached 90 compared to those who did not).

    Some factors associated with survival were common to both genders, whereas some others appeared gender specific. For men, tenant status (hazard ratio, HR=1.46), former or current smoking (HR=1.17), disability (respective HR of 1.50, 1.78 and 2.81 for mild, moderate and severe level), dementia (HR=1.51), a recent hospitalisation (HR=1.32), dyspnoea (HR=1.32), and cardiovascular symptoms (HR=1.15) were associated with lower chance of becoming nonagenarian. Conversely, regular physical activity (HR=0.74) was associated with higher chance of survival.

    For women, the presence of a professional help (HR=1.19), living arrangements (HR=1.29 and HR=1.33), disability (respective HR of 1.55, 1.95 and 2.70 for mild, moderate and severe disability), dementia (HR=1.54), a recent hospitalisation (HR=1.19), diabetes (HR=1.49), and dyspnoea (HR=1.20) were associated with lower chance of becoming nonagenarian. Conversely, satisfaction of level income (HR=0.87), comfortable housing (HR=0.81), length of living in the dwelling (HR=0.80 upper to 6 years), regular physical activity (HR=0.89) and a medium (HR=0.79) or good (HR=0.68) subjective health, were associated with higher chance of becoming nonagenarian.


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