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Older Parents, Probably Not So Good

Posted: April 24, 2011 at 3:53 pm


One of the predictions of the reliability theory of aging and longevity is that we are all born damaged. Reliability theory evolved from the theories used to predict failure in mechanical systems; as such, it is a less an attempt to explain the roots of aging and more an attempt to frame an understanding of the way in which accumulating damage at the most fundamental levels of our biochemistry produces the observed patterns of aging.

The models of reliability theory only match up with reality if we assume that life starts with a certain level of preexisting biological damage, and that damage goes some way to determining later health and life expectancy. What happens in early life matters a great deal, it seems. This is why we are interested in such topics as the potential effects of solar radiation on the unborn, and the degree to which historical increases in longevity can be explained by a lower childhood burden of chronic disease.

I noticed another interesting data point today in an open access paper: a possible marker for the biological cost of being born to an older mother - something that we know bears an increased risk of health issues.

Parental ages and levels of DNA methylation in the newborn are correlated:

Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. Only a proportion of these increased risks among the children of older parents can be attributed to nondisjunction and chromosomal rearrangements.

We found that methylation levels [associated with] 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. ... Genes associated with [cancer] are significantly over-represented among the genes correlated with maternal age, and this suggests a link to known increased risks of cancer among the children of older parents. Similarly, gene functions related to neurodevelopment and neuroregulation are over-represented among the strongly correlated genes, and this may have relevance to the increasing risk of neurodevelopmental and psychiatric disorders in offspring as parental ages increase.

Biotechnology will be a great leveler of opportunity, a grand remover of adversity, offering the chance to repair deleterious consequences of ancestry, birth, and other biological circumstances beyond our control. Systematic altereration of DNA methylation will likely be a commonplace medical technology of the late 2020s, for example. This and many other potentially beneficial manipulations of DNA are almost within reach of the most advanced research groups today - and the biotechnologies of ten or fifteen years from today will far cheaper and more capable than the best machinery now available.

The CRONA Study

Posted: at 3:53 pm


A look at current research on the definite health and potential longevity benefits of calorie restriction in humans: "Animals who consume fewer calories live longer and healthier lives. Now, a seminal study at the University of California, San Francisco (UCSF) is testing whether the same is true for extreme dieters. The calorie restriction study centers on two primary questions: What allows people to live in a manner many consider food deprived? And does it slow down aging? Called CRONA (Caloric Restriction with Optimal Nutrition and Aging Study), the investigation is probing the biological processes affected by extremely low caloric intake, including the impact on telomeres - tiny pieces of DNA that protect cell chromosomes. Short telomeres have been linked to a host of health problems including diabetes, heart disease and premature death. The UCSF study is the first to broadly examine the psychological profile of successful extreme dieters, gauging how their cognitive sharpness, impulse control, stress and personality differ from normal eaters and overeaters. ... Testing and data collection will continue through summer. The scientists are still recruiting control subjects who are either obese or 'free eaters' - not restricting food intake but not overweight. Interested parties can email cronastudy@gmail.com. ... We need information about what it takes to change your eating pattern for a long time. There are so many diets out there - people lose weight for six months, then regain it. We need to study what it is about the calorie restrictors that makes them able to do this for years and years." The new information on the biological response to calorie restriction is, I think, much more valuable than yet another study on willpower in humans.

Link: http://www.ucsf.edu/news/2011/04/9740/extreme-dieting-does-it-lead-longer-lives

A Look at Garage Biotechnology

Posted: at 3:53 pm


Small scale efforts by a widespread people outside the academic and industry communities, and open and largely free access to plans and data are the future of biotechnology. It is a data-driven field, and will ultimately look just like the open source software community does today: "Following in the footsteps of revolutionaries like Steve Jobs and Steve Wozniak, who built the first Apple computer in Jobs's garage, and Sergey Brin and Larry Page, who invented Google in a friend's garage, biohackers are attempting bold feats of genetic engineering, drug development, and biotech research in makeshift home laboratories. ... For a few hundred dollars, anyone can send some spit to a sequencing company and receive a complete DNA scan, and then use free software to analyze the results. Custom-made DNA can be mail-ordered off websites, and affordable biotech gear is available on Craigslist and eBay. ... biohackers, like the open-source programmers and software hackers who came before, are united by a profound idealism. They believe in the power of individuals as opposed to corporate interests, in the wisdom of crowds as opposed to the single-mindedness of experts, and in the incentive to do good for the world as opposed to the need to turn a profit. Suspicious of scientific elitism and inspired by the success of open-source computing, the bio DIYers believe that individuals have a fundamental right to biological information, that spreading the tools of biotech to the masses will accelerate the pace of progress, and that the fruits of the biosciences should be delivered into the hands of the people who need them the most."

Link: http://www.technologyreview.com/biomedicine/37444/

The Importance of Improvement

Posted: at 3:53 pm


It is unfortunate and noteworthy that the loudest institutional voices in Western culture seem to have an aversion to human enhancement. It is the ideal of equality run rampant, heading for its inevitable Harrison Bergeron endpoint - equality by leveling down to the lowest and preventing new heights from being achieved. Destruction is the only thing that politicians are really good at, sad to say, and egalitarianism, much like communism, is pretty in its abstract ideals but horrific when put into practice:

This rejection of human enhancement is in essence a rejection of the urge to improvement - and is thus one of a number of important hurdles standing in the way of widespread support for the development of rejuvenation biotechnology. Living longer than your parents did? That's an enhancement, and a great many talking heads would like to see laws written to prevent such technologies from ever seeing the light of day.

Yet the urge to improvement is everywhere else in evidence in our societies, as noted in this subtle injection of transhumanist ideals into the Discover Magazine website:

Just because I'm not ill [and] not injured, doesn't mean that I am, by default, as healthy as I could be. For some bizarre reason, we don't think about our bodies that way when it comes to health care and self improvement. We don't pursue excellent health the way we strive to be better in our hobbies and work. So, where did we get the idea that mediocre health is good enough?

...

But here's the interesting thing: neither the US nor the UK have regulations in place for prescription pharmaceuticals that are not therapeutic. Drugs that don't cure an illness but still have a beneficial effect have one of two paths: either find an illness they do cure or invent an illness that the drug seems to cure. An example of the latter is Viagra. I don't care what the DSM says, erectile dysfunction is not real illness. But Viagra works. It doesn't "cure" anything, but it sure makes a lot of people's lives better, which is [a] great thing. But it's a massive problem that there is no way for drugs that make our health better to find their way onto the market. And there in lies the problem. Save vaccines, modern medicine just doesn't know what to do with medicine that prevents disease or improves a person's life.

...

Prevent and improve. Those are the two words I'd argue are most underused in every other aspect of human health care. Why does self-improvement not include pharmaceuticals that make us smarter or stronger or happier? Because we've been convinced and told and reminded and scolded that taking a pill means something is wrong with you.

And so to aging and longevity. The bureaucrats of the FDA do not recognize aging as a disease, and so will not approve treatments for it. In a culture that is hostile to human enhancement, winning support for the reversal of aging will be that much harder. This is one of many ways in which freedom matters greatly in medical research. Under the systems of regulation in place in the largest markets of the world, researchers and commercial developers are far from free to turn proven science into commercial products, and far from free to convince their fellow countrymen to try something new.

We humans are the species that improves ourselves and creates value from our surroundings. That is our defining characteristic - and yet, paradoxically, so much time and effort in this day and age is devoted to sabotaging the engines of progress.

The Promise of Stem Cell Rejuvenation

Posted: at 3:53 pm


Stem cell function, necessary to maintain tissue, declines with age. This most likely a part of the evolved balancing act between suppression of cancer and the need to keep tissues repaired and working - as you grow older, forms of molecular damage accumulate, increasing the risk of cancer resulting from the normal operations of cellular proliferation. That balance can already be shifted in mice in very beneficial ways, giving both less cancer and longer lives. While these are the early days yet, in our future lies a fusion of the fields of cancer research and stem cell science that will do the same for humans: "Adult stem cells exist in most mammalian organs and tissues and are indispensable for normal tissue homeostasis and repair. In most tissues, there is an age-related decline in stem cell functionality but not a depletion of stem cells. Such functional changes reflect deleterious effects of age on the genome, epigenome, and proteome, some of which arise cell autonomously and others of which are imposed by an age-related change in the local milieu or systemic environment. Notably, some of the changes, particularly epigenomic and proteomic, are potentially reversible, and both environmental and genetic interventions can result in the rejuvenation of aged stem cells. Such findings have profound implications for the stem cell-based therapy of age-related diseases."

Link: http://jcb.rupress.org/content/193/2/257.long

Time Waits for No One

Posted: at 3:52 pm


A reminder: "Biological aging is the greatest health threat to humanity today. It causes more disease and suffering in the world than all infectious diseases (HIV, malaria, etc.) or any other cause (e.g. poverty, war, natural disaster, etc.). The inborn aging process causes cancer, heart disease, stroke, AD, joint pain, vision and hearing impairment, etc. The harms of senescence (even if we exercise and eat a healthy diet) are certain, severe and universal. The diseases of aging afflict both rich and poor, and developed and developing countries. And, unless the biological clocks we have inherited from our Darwinian past are modified, it is highly likely that all future generations of human beings that shall ever live on this planet will suffer one or more of the diseases of aging. In light of the unique health challenges facing the world's aging populations, the most important knowledge humans can acquire today is knowledge about the biology of aging: why do we, as a species, age at the rate we do? why does aging leave our bodies and minds susceptible to disease? And, most importantly, how can we retard or ameliorate the harmful effects of biological aging?"

Link: http://colinfarrelly.blogspot.com/2011/04/time-waits-for-no-one.html

Measuring the Benefits of Good Lifestyle Choices

Posted: at 3:52 pm


For everyday, average, healthy people, leading a good lifestyle makes a sizable difference both to your life expectancy and your chances of suffering the common age-related diseases in years to come. Refrain from smoking, regular moderate exercise, and a diet low in calories that still provides optimal nutrition - thereby avoiding the build up of visceral fat that happens on the way towards obesity - and you will gain a greater benefit than any presently available medical technology can offer.

For example:

A study of more than 100,000 men and women over 14 years finds nonsmokers who followed recommendations for cancer prevention had a lower risk of death from cancer, cardiovascular disease, and all-causes.

...

The participants were scored on a range from 0 to 8 points to reflect adherence to the American Cancer Society (ACS) cancer prevention guidelines regarding body mass index, physical activity, diet, and alcohol consumption, with 8 points representing adherence to all of the recommendations simultaneously.

After 14 years, men and women with high compliance scores (7, 8) had a 42% lower risk of death compared to those with low scores (0-2). Risk of cardiovascular disease death were 48% lower among men and 58% lower among women, while the risk of cancer death was 30% lower in men and 24% lower in women.

The best we can presently do for our health and longevity in this grand age of biotechnology is still exactly the same as the best was for our grandparents, and that is disappointing. There is a gaping chasm between the exciting advances and technology demonstrations taking place in laboratories and what becomes available for commercialization - or rather what the regulators grudging permit to become available for commercialization. The future will include rejuvenation biotechnology that can repair the damage of aging. That technology is clearly envisaged and understood today, but progress towards its development and deployment remains frustratingly slow.

As always, the way to change this situation lies in money and action: help out, persuade people to help out, and give your time and resources to speed matters along.

Investigating Muscle Repair and Maintenance

Posted: at 3:52 pm


A number of research groups are looking into ways to manipulate muscle regeneration and maintenance, and an advance here could be useful as a therapy to address age-related loss in muscle mass and strength: "Researchers have long questioned why patients with Duchenne muscular dystrophy (DMD) tend to manage well through childhood and adolescence, yet succumb to their disease in early adulthood, or why elderly people who lose muscle strength following bed rest find it difficult or impossible to regain. Now, researchers [are] beginning to find answers in a specialized population of cells called satellite cells. Their findings [suggest] a potential therapeutic target for conditions where muscle deterioration threatens life or quality of life. ... Suspecting a genetic switch that might turn off satellite cell proliferation in these circumstances, the scientists looked to a gene called Ezh2, known to keep the activity of other genes in check. When they genetically inactivated Ezh2 in satellite cells of laboratory mice, the mice failed to repair muscle damage caused by traumatic injury - satellite cells could not proliferate. Ezh2 expression is known to decline during aging, and the new research in mice suggests that therapies to activate Ezh2 and promote satellite cell proliferation might eventually play a role in treating degenerative muscle diseases. ... in the elderly, tweaking the gene in satellite cells would not increase their lifespan, but could increase their quality of life by helping to prevent falls and enabling them to move and walk better and go about their daily activities."

Link: http://www.nih.gov/news/health/apr2011/niams-15.htm

The Work of Michael Rose

Posted: at 3:52 pm


A Science 2.0 article looks at the work of researcher Michael Rose over past decades: "Over the years, Rose and his lab have bred fruit flies to live four times the life span of an average fruit fly. Reasoning from those studies, Rose has proposed that, because the life spans of fruit flies have the genetic capability to be extensively prolonged, human life can be manipulated in the same way. ... Wattiaux was a French scientist working at the University of Leuven in Belgium. His study used the same fruit flies that Rose had been working with ... Wattiaux found that when he made each new generation of fruit flies that were the offspring of old parents exclusively, the flies showed an increased life span after each generation. But Wattiaux didn't know why his fruit flies lived longer. He felt that longevity increased because of a nongenetic effect, but he didn't have any direct evidence. Rose did. Wattiaux's results, he saw, showed the importance of the force of natural selection. He believed that, because natural selection stops working at a late age and fails to eliminate genes with detrimental effects, these bad genes would not be removed by natural selection. Instead, they would accumulate. In populations that reproduce early, natural selection declines early. Alternatively, populations that are old when they reproduce will continue to be subject to powerful selection until they begin to reproduce. Thus, by allowing older flies to reproduce over generations, natural selection would continue to choose the flies that are able to breed at a later age - the fittest flies."

Link: http://www.science20.com/forever_fly/forever_fly_forever_diet-78126

Muddy Waters When it Comes to Quahog Biochemistry and Longevity

Posted: at 3:52 pm


Yes, we're back to clams again: four hundred year old clams in this case. The ocean quahog, Arctica islandica, is a very long-lived bivalve that, like other unusually long-lived species, is attracting the attention of researchers. How is it that these animals manage to live so much longer than their near relatives? You'll find some background reading in the archives:

Researchers to date have focused on resistance to oxidative damage in quahogs, but the more research is done, the more ambiguous that picture becomes. It doesn't seem to be the case that we can simply point to very high levels of antioxidants or an aggressive antioxidant response that preserves cells from the accumulating damage caused by oxidative byproducts of metabolism. In many ways this parallels research into the biochemistry of the naked mole-rat: the initial focus on examining natural antioxidants gave way to the present view that their comparatively long life span depends on differences in the construction of their vulnerable cell membranes. They are better built in the places where it matters - their cells are buzzing with reactive oxidant compounds, but their resistant cell membranes shrug it off.

That may be the case for the quahog as well, but researchers aren't there yet. This recent paper manages to continue the present trend of muddying the waters:

We assess whether reactive oxygen species production and resistance to oxidative stress might be causally involved in the exceptional longevity exhibited by the ocean quahog Arctica islandica. We tested this hypothesis by comparing reactive oxygen species production, resistance to oxidative stress, antioxidant defenses, and protein damage elimination processes in long-lived A islandica with the shorter-lived hard clam, Mercenaria mercenaria. We compared baseline biochemical profiles, age-related changes, and responses to exposure to the oxidative stressor tert-butyl hydroperoxide (TBHP).

Our data support the premise that extreme longevity in A islandica is associated with an attenuated cellular reactive oxygen species production. The observation of reduced protein carbonyl concentration in A islandica gill tissue compared with M mercenaria suggests that reduced reactive oxygen species production in long-living bivalves is associated with lower levels of accumulated macromolecular damage, suggesting cellular redox homeostasis may determine life span. Resistance to aging at the organismal level is often reflected in resistance to oxidative stressors at the cellular level.

Following TBHP exposure, we observed not only an association between longevity and resistance to oxidative stress-induced mortality but also marked resistance to oxidative stress-induced cell death in the longer-living bivalves. Contrary to some expectations from the oxidative stress hypothesis, we observed that A islandica exhibited neither greater antioxidant capacities nor specific activities than in M mercenaria nor a more pronounced homeostatic antioxidant response following TBHP exposure. The study also failed to provide support for the exceptional longevity of A islandica being associated with enhanced protein recycling.

Which is really saying little that is new and definitive - just better ruling out some of the options. The quahog could be producing fewer oxidants, or it could be efficiently mopping up oxidants at their source in the mitochondria due to a natural source of localized antioxidant compounds. In either case, that says nothing about how it or its cells might react to an externally provided and artificial source of oxidative stress like TBHP. Given the present pace of work, however, I'd expect that researchers will have developed a well-supported consensus explanation for the extreme longevity of this species and the naked-mole rat by the time 2020 rolls around.

International Stem Cell Corporation Updates on Marketing Strategy of Its Subsidiary Lifeline Skin Care

Posted: at 3:52 pm


International Stem Cell Corporation (OTCBB:ISCO) http://www.internationalstemcell.com, a California-based biotechnology company focused on therapeutic and research products, announced today the selection of the Richards Partners as agency of record for its wholly owned subsidiary Lifeline Skin Care, Inc. ("Lifeline"). Lifeline offers luxury anti-aging skin care products based on its proprietary stem cell technology. Based in Dallas, the Richards Partners is the nation's largest independent branding agency.

Lifeline's skin care products were developed by a team of ISCO research scientists in collaboration with world-renowned cosmetic experts, and offer a comprehensive approach to skin care using patent pending moisture serums for day and night use. Made with human parthenogenetic stem cell extracts, the serums deliver anti-aging benefits, resulting in healthier and younger-looking skin. These products were launched in November 2010 and are available for purchase through the http://www.lifelineskincare.com website and selected luxury spas across the United States.

Adding Richards Partners to the Lifeline Skin CareTM team is part of Lifeline's plan to build on its initial successful product launch last year, and the Web based sales that have followed, by initiating a series of new marketing campaigns to further develop the Lifeline Skin CareTMbrand identity. These new marketing initiatives include traditional print and news media campaigns, as well as a new digital strategy focused on Internet and social media. "We are looking forward to working closely with the Richards Partners and leveraging their expertise in these areas to enhance the profile of Lifeline Skin CareTM and its revolutionary new skin care products," says Lifeline CEO Ruslan Semechkin, PhD. "Building a globally recognizable brand is a long-term process and this is an important step towards creating Lifeline's name. We believe this is a good time to begin these campaigns and continue our sales momentum resulting from our successful initial launch," Dr. Semechkin continued.

As previously announced the Mauldin Group, Lifeline's marketing partner, will be managing the day to day relationship with the Richards Partners and planning additional direct marketing initiatives similar to the successful initial launch in 2010. Tiffani Mauldin-Frederick, marketing partner of Lifeline Skin CareTM, says, "We're excited about working together with Richards Partners. We believe the collaboration will provide additional momentum and increase brand recognition for Lifeline Skin CareTM and help educate the public about the revolutionary science behind these products."

ABOUT INTERNATIONAL STEM CELL CORPORATION (ISCO.OB)

International Stem Cell Corporation is a California-based biotechnology company focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing sexes, ages and racial groups. This offers the potential to create the first true stem cell bank, UniStemCell™, while avoiding the ethical issue of using fertilized eggs. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at ISCO's website, http://www.internationalstemcell.com.

To subscribe to receive ongoing corporate communications please click on the following link:http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0.

FORWARD-LOOKING STATEMENTS

Statements pertaining to anticipated developments, product introduction plans and related support, the potential benefits of products, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products and the management of collaborations, regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.

Key Words: Stem cells, parthenogenesis, biotechnology, skin care, anti-aging

http://cts.businesswire.com/ct/CT?id=bwnews&sty=20110419005649r1&sid=14230&distro=ftp

International Stem Cell Corporation
Kenneth C. Aldrich, Chairman
1-760-940-6383
kaldrich@intlstemcell.com

or
Lifeline Skin Care, Inc.
Ruslan Semechkin, PhD, President & CEO
Vice President, ISCO
ras@intlstemcell.com

Progress is Forged Over the Background Hum of Whining Ethicists

Posted: April 17, 2011 at 3:52 pm


The problem with ethics as a profession is exactly that it has become a profession: the salaried ethicist knows that his continued employment depends upon finding problems with research and development. Money, even modest amounts of the stuff, is a powerful incentive. So where there are no problems, there are still groups of people who are effectively being paid to invent problems - and you wonder why medical science isn't moving as fast as it might be.

This form of institutional corrosion is well entrenched throughout the Western world now, of course, and so you'll see plenty of things like this open access whine-slash-justification-for-a-paycheck:

Optimistic predictions of the feasibility and effectiveness of life extension should be critically reviewed in the light of their ethical and social implications. Some anti-aging scientists claim that arguments against anti-aging medicine will simply be dismissed by research outcomes. We would claim that the problem is not with the availability of results, but with defining the nature of what we consider "results".

The idea that life extension research will necessarily translate into what some judges interpret as a result (i.e. the cure of aging) is problematic, because the translational process from potential life extension interventions into reality is not only a matter of science. Suppose we have laboratory advances that are promising for the future translation of laboratory work to the clinic. This result would matter scientifically, but would not solve the ethical and social questions of life-extending interventions. Even if we should succeed in the laboratory, the problems of equitable access to such interventions, the impacts of the future implementation of life extension on health care systems, the risk of pressure to make use of life extension techniques - all these issues will still be with us. Here, more than ever, it must be stressed that the "nature" of what we consider "results" matters not only scientifically, but also ethically and socially. Ethical and social debate on these issues is therefore much needed, along with scientific research and discussion.

Roughly translated: "I don't actually know enough about contemporary longevity science to write about it comprehensively or well, but I do know how to write successful grants. Please pay me and my colleagues more money rather than putting those resources to work on actual research." The middle section of the paper is particularly offensive on that count, an incomplete overview that plays up the bad and the unknown while failing to mention important topics such as SENS, systems biology, tissue engineering, and so on and so forth. There are admittedly far worse things going on in the world these days than the efforts of a legion of minor parasites who've manage to redirect research funding to build an industry that actively opposes research, but the noisy parasitism of the ethics profession manages to be more aggravating than its cost should make it.

Strange things happen to cultures when they lose sight of what matters, begin to value abstractions such as "society" over real individuals, and empty talk over tangible progress. I'd say it's a form of collective cabin fever brought on by the shrinking world and the absence of a frontier: with no hard-to-reach destination for the best, brightest, and most motivated to head for when matters become less than tolerable, there is no escape valve to prevent a network of diverse cultures from nonetheless degenerating in lockstep. The only form of protest that really matters in the long term - when it comes to applying pressure for change - is emigration to a remote region in order to build better lives. The sooner that the next new frontier is opened by technological progress in orbital flight the better in my view.

Calorie Restriction and Core Body Temperature in Humans

Posted: at 3:52 pm


Another of the observed effects of calorie restriction in lower animals is shown to exist in humans as well: "Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. ... Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups ... Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging."

Link: http://www.impactaging.com/papers/v3/n4/full/100280.html

Industrialization of Tissue Engineering

Posted: at 3:51 pm


Economies of scale apply to all endeavors, including the production of human tissue: "The high-tech production lines of [a] laboratory in Germany began moving this week turning out a unique product - human skin. Nicknamed 'The Flesh Factory' by the boffins who work at the Stuttgarter Fraunhofer-Institute, it aims to produce 5,000 circles of skin as big as a one-euro cent every month. Costing around 45 pounds each, when the skin circles are perfected they will be sold to hospitals and clinics around the world for life-saving operations. Project leader Professor Heike Walles, 48, has devoted her whole life to the goal of reproducing human skin on an industrial scale - to save human life and protect animals; it can be used for the kind of testing currently requiring the sacrifice of live creatures. ... Until now, methods of culturing tissue like that used for skin transplants have been very expensive. Most of the steps are carried out manually, which means that the process is not particularly efficient. ... The new production line is entirely mechanical and controlled by computers. ... The process works like this; a biopsy - a sample of human tissue - is checked for sterility. A gripper arm then transports the biopsy into an automated cutting device. The machine snips the biopsy into small pieces, isolates the different cell types, stimulates their growth, and mixes the skin cells with collagen. A three-dimensional reconstruction of the different skin layers is produced with the aid of a special gel matrix - and the skin is ready. In the final step, the machine packages the cells for shipment. Alternatively, the tissue can be cryopreserved - that is, deep-frozen and stored for later use."

Link: http://germanherald.com/news/Allan_Hall's_Germany/2011-04-13/647/The_Flesh_Factory_goes_online

Reverse Engineering Protofection as a First Target for the Vegas Group

Posted: at 3:51 pm


The Vegas Group is a yet-to-be-built community initiative intended to bring longevity science to the open biotechnology and DIYbio communities - and from there reverse engineer and make ready for human use the most promising longevity-enhancing technologies demonstrated in mice in the laboratory. We are entering an age of medical tourism, and the clinics and laboratories of Asia will be happy to accept business and open source biotechnologies generated by DIYbio work in the US. At this stage, I'm still thinking through the project: breaking it down into manageable chunks, and considering what I should work on first:

The path to this future involves networking and community building in a whole new and different direction from that taken by much of the longevity advocacy community - and the construction of a codex of information, a how-to manual of recipes for replicating specific products of the formal research community in longevity science. ... any step one for me will involve considering the codex: what it is, and how it will be constructed, maintained, and made useful to the seeds of what will be the Vegas Group - however that organization ultimately comes about, and whatever form it ultimately takes.

As the cost of biotechnology falls, so is the door opened to much wider development and innovation, wherein lab cooperatives host a mix of hobbyists, moonlighting professionals, and semi-professionals who collaborate on a range of their own projects. Ultimately, low-cost desktop biotech toolkits will be developed and a community of tens or hundreds of thousands of developers will contribute from their homes - just as is the case for open source software development today. With computers in mind, a good historical analogy for the present state of the small DIYbio community is in fact the Homebrew Computer Club in the mid 1970s, prior to the introduction of the first popular personal computer kit. Some small but enthusiastic individuals and groups are designing, building, and selling biotech hardware - such as PCR machines - that will ultimately be the components of a home laboratory, but matters are not yet at that stage of take-off that will see dozens of companies founded and many more people join the community in a short period of years. That lies ahead. The wave is coming, in its own time, and I would like to be positioned to take advantage of it.

All journeys start with the first steps, and I'm in favor of incremental approaches to development. Make something small, a minimum viable product that is the most elementary building block that can stand on its own and still contribute to the ultimate goal. Release it, obtain feedback, and then start on the next building block - and repeat that process until you have as fully as possible realized your initial vision. There will be much to learn along the way, and small building blocks coupled with "release early, release often" make that learning less painful.

Given a large idea, the challenge is often finding that starting point. From the broad high level outline of the Vegas Group, I focused on the codex: the necessary how-to documents and body of knowledge that will enable people to participate. As a general rule, technical communities are terrible at documentation - and that lack of documentation is a real hurdle to recruitment and growth. It could be argued that the DIYbio community isn't yet at the point where it could benefit greatly from a codex: there are other tasks to be completed first relating to hardware. But time is ticking, and progress is being made. The period of being too early won't last forever, and establishing even the skeleton of a practical longevity science codex at hobbyist or non-profit speed will be a process that takes years.

The codex itself is a very large project: something large enough to found a company on in and of itself. There are any number of questions: how best to discover the business models that work to efficiently produce accurate reverse engineering from published papers on longevity-related biotechnology; how best to structure the information presented; how to organize writers and researchers; how to even assemble and prioritize the list of materials needed; and so on ad infinitum.

Thus a fairly narrow initial project for the codex must be identified, so that the first group of volunteers to work on it can run into all the brick walls and fall into all of the potholes without risking a great deal if it all fails. Small projects are easy to scrap, rework, and start over if necessary - and that is a tremendous advantage when you don't yet know the detailed recipe for success. Along the way the volunteers will come to an understanding of how best to make assembly of the broader codex work as a process.

What is this first codex project, though? I propose that reverse engineering and documentation of mitochondrial protofection is a good candidate. This is a technique by which mitochondrial DNA is replaced throughout an individual's cells, and was first demonstrated in mice back in 2005. As you might know, progressively accumulated damage to mitochondrial DNA is one of the causes of aging, as described by the mitochondrial free radical theory of aging. Future rejuvenation biotechnology must include a way to either permanently work around this form of damage, such as through the methodology advocated by the SENS Foundation, or periodically repair it - say once every two to three decades.

Why protofection? In a nutshell:

  • It is comparatively easy to explain to a non-technical audience.
  • It fits with the SENS vision for rejuvenation biotechnology.
  • It has already been demonstrated to work, so at least one group of researchers knows exactly how to do it.
  • It is old enough that this and related knowledge may have spread somewhat, making it more amenable to reverse engineering.

Protofection works in mice, but since that demonstration six years ago next to nothing has been heard of it - just a few publications indicative of a slow exploration in search of possible FDA-approved applications. The FDA does not consider aging a disease, however, and therefore its regulators will not approve any treatment that aims to intervene in aging or achieve rejuvenation. That unfortunate fact is well known, and thus there is little funding available for attempts to treat aging: potential technologies are instead subverted into the development of limited treatments for late stage age-related diseases. The silence regarding protofection is probably another good example of the way in which the present regulatory apparatus holds back progress, as developing protofection for safe general human use is an obvious course of action based on the weight of evidence linking mitochondrial DNA damage and aging. Yet it isn't happening.

Given that a number of years have passed since the viability of protofection was demonstrated, it should be an easier target for reverse engineering and documentation of processes than more recent developments. By which I mean that it should be easier to find researchers and post-graduates unconnected with the work who nonetheless know enough to write on the topic.

Protofection is also (I hope) narrow enough not to generate a true mountain of supporting needs in terms of how-to documents. Part of the process of discovery is to understand how to develop the initial list of documents required for the codex, starting from a high-level goal like "let's reverse engineer protofection, make reproducing it comprehensible to the semi-professional DIYbio volunteer, and release that documentation under a Creative Commons license" and working all way down to the brass tacks and petri dishes. Protofection, while something that can be explained in a few short sentences, stands at the top of a sizable pyramid of techniques and knowledge in biotechnology: how to work with DNA, how to manage your own laboratory equipment, how to keep cell cultures, and so on for a long list of topics.

If this takes a few years to get right, that's fine by me. It will provide a blueprint for doing the same to other areas of biotechnology, and by that time there should be more people interest in helping out - both for longevity science and for their own areas of interest.

Vegetarianism, Or Less Body Fat?

Posted: at 3:51 pm


Here is an example of a research commentary that misses the forest for the trees: "Vegetarians experience a 36 percent lower prevalence of metabolic syndrome than non-vegetarians, suggests new research ... Because metabolic syndrome can be a precursor to heart disease, diabetes, and stroke, the findings indicate vegetarians may be at lower risk of developing these conditions. Metabolic syndrome is defined as exhibiting at least three out of five total risk factors: high blood pressure, elevated HDL cholesterol, high glucose levels, elevated triglycerides, and an unhealthy waist circumference. ... while 25 percent of vegetarians had metabolic syndrome, the number significantly rises to 37 percent for semi-vegetarians and 39 percent for non-vegetarians. The results hold up when adjusted for factors such as age, gender, race, physical activity, calories consumed, smoking, and alcohol intake. ... On average, the vegetarians and semi-vegetarians were three years older than non-vegetarians. Despite their slightly older age, vegetarians had lower triglycerides, glucose levels, blood pressure, waist circumference, and body mass index (BMI). Semi-vegetarians also had a significantly lower BMI and waist circumference compared to those who ate meat more regularly." Given the broader context of what is known about the effects of body fat on long-term health, the plausible mechanism here looks to be related to the amount of visceral fat rather than anything to do with diet per se.

Link: http://www.eurekalert.org/pub_releases/2011-04/llua-vmb041311.php

Growing Kidneys From Stem Cells

Posted: at 3:51 pm


Progress in tissue engineering: "scientists have created human kidneys from stem cells ... The artificial organs were created in a laboratory using human amniotic fluid and animal foetal cells. They are currently half a centimetre in length - the same size as kidneys found in an unborn baby. [Scientists] hope they will grow into full-size organs when transplanted into a human. ... It sounds a bit science fiction-like but it's not. The idea is to start with human stem cells and end up with a functioning organ. We have made pretty good progress with that. We can make something that has the complexity of a normal, foetal kidney ... The research team hope that doctors will eventually be able to collect amniotic fluid, which surrounds the growing embryo in the womb, when a baby is born. This will then be stored by scientists in case that person develops kidney disease later in life. The fluid can then be used to create a matching kidney. Creating an organ using a patient's own stem cells solves the problem of having to use powerful immunosuppressant drugs to stop the body rejecting a another person's kidney. ... the technology could be ready for use on humans in around 10 years." By which time it will probably be unnecessary to collect amniotic fluid, as the signals and chemicals it provides will be understood and reproduced.

Link: http://www.telegraph.co.uk/health/healthnews/8443740/Scientists-create-human-kidneys-from-stem-cells.html

Critiquing the Practice of Cryonics

Posted: at 3:51 pm


Over at Chronosphere you'll find a weighty set of posts that aim to provide a foundation for critiquing cryonics at the organizational level of achieving consistently good cryopreservations, and the development of professional organizational cultures and processes - such as record-keeping - required to support that goal. All industries require ongoing initiatives that provide solid, constructive critiques of present practice, for otherwise how are the participants to progress and improve themselves?

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 1:

The goal of this series of articles is to equip the reader with the tools necessary to make an accurate assessment of the quality of care cryonics patients, both individually and as a group, are receiving from their respective cryonics organizations.

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 2:

In a very real sense, that care starts the moment the member/patient experiences his first contact with the cryonics organization that will ultimately cryopreserve him. The tenor of that first contact will likely determine the nature and course of the member's subsequent interaction both with cryonics and his cryonics organization. If cryonics is presented as a developed product that is costly but nevertheless fairly routine, say like buying a home or an automobile, that's very likely how it will be subsequently be treated. If, on the other hand, there is heavy emphasis on the lack of infrastructure to provide help in an emergency and the need to exercise both personal responsibility and personal preparedness, outcomes will likely differ - at least statistically, if not in each individual case.

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 3:

not only is it important that those caring for the patient know what is expected of them, the cryonics organization must also know what the family/caregiver's needs are, both logistically and psychologically. Cryonics is unfamiliar territory for family, and the procedures attending [the preparatory period immediately prior to cryopreservation] can perturb what in many cases will be a fragile emotional and psychological equilibrium in the patient's home life. Organizations that fail to establish rapport, and work to ascertain and meet the needs of the patient's family, risk non-cooperation, obstruction and even litigation. Seemingly small details, such as protecting flooring or furniture from water damage, or arranging for a few minutes of private "alone time" with the patient before he is removed from the home or care facility after acute stabilization, can mean the difference between heartfelt assistance, and bitter belligerence from the next of kin.

The quotes above hit some of the points I have had in mind in past years when discussing the need for cryonics organizations to (a) become more professional in character, and (b) form up a better product offering for customers, one that provides more in the way of service and guidance than is presently the case. That theme continues into the last of the four posts, linked below.

You be the Judge: Understanding and Evaluating the Quality of Human Cryopreservations from Cryonics Organization Literature and Case Report Data, Part 4:

Nevertheless, the real solutions to the problems discussed here are not easy, because they demand the acquisition of professionalism, knowledge, and skill in the context of cryonics as medicine. I personally believe that Jerry Leaf and I came very close to doing that in the decade between 1981 and 1991. But we failed. Why we failed will be discussed at a later time. Suffice it to say that the problem of maintaining professionalism is a nettlesome one in medicine, engineering and other demanding disciples that are vastly more developed than cryonics is today, and there will be no quick fixes.

"No quick fixes" is a conclusion I agree with. Nothing worthwhile is quick and painless to achieve, and even small industries change slowly when it comes to company cultures. The only reliable path to faster change involves money, as change follows rapid growth in the number of paying customers in any human endeavor. Unfortunately that growth remains elusive for cryonics providers, just as it has throughout that past decades. From where I stand, I'd say that the best near-term path to the goal of transformative growth in revenue lies in developing spin-off technologies in cryobiology and related fields - but that's an opinion offered without any great insight into the inner workings of the industry as it exists today. It is simply taken from the standard business texts: if you've consistently failed to achieve good growth with option A, then perhaps it's time to try options B, C, and D.

Klotho in Humans

Posted: at 3:50 pm


You might recall the identification of klotho as a longevity-related gene in mice and other lower animals in recent years. Here is a study on levels of klotho in humans: "The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans. ... We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. ... During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho [had] an increased risk of death compared with participants in the highest tertile of plasma klotho ... In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans." Given the number of adjustments there, I'd like to see a confirming study - and for preference one that explicitly took into account calorie intake as well. Just because you see the expected result is no reason to abandon the usual level of caution needed when reading the output of the scientific method.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21474560

Never Too Late to Exercise: the PROOF Study

Posted: at 3:50 pm


Even at older ages, exercise is a still very important - as demonstrated by the degree to which it influences ongoing health in later stages of life, just as it does in earlier stages in life. "It is not sufficient simply to live longer. One of the current priorities for public health is to how to maintain good quality of life for longer. This has given rise to the concept of 'successful aging' generating a turning point in our thinking about aging, which is no longer seen as an inevitable decline. ... Physical activity has a pleiotropic effect and is a significant factor in successful aging. This study aims to quantify the relationship between the physical activity of a 65-year-old cohort and the level of life satisfaction and self-rated health 7 years later. A total of 988 questionnaires were sent by mail to a representative sample of healthy pensioners. Life satisfaction and health status were estimated on two visual analogical scales in answer to the following questions: (1) How would you estimate your state of health? and (2) Are you generally satisfied with your life? The level of physical activity was estimated using a questionnaire which enabled us to calculate: Daily energy expenditure (DEE) [and] VO2 peak. ... Energy spent in activity and VO2 peak estimated from DEE, measured at the age of 65, appear to be strong predictors of well-being 7 years later."

Link: http://dx.doi.org/10.1089/rej.2010.1101

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