Longevity Meme Newsletter, December 20th 2010

December 20th 2010

The Longevity Meme 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 the Longevity Meme.



- Changes Underway at Fight Aging! and the Longevity Meme
- Advancing Biotechnology and the Utility of Savings
- Longevity in the Laboratory
- SENS Foundation is Hiring
- Reports From the 2020 Bay Area Aging Meeting
- Latest Headlines from Fight Aging!


As you may have noticed, much of the Longevity Meme has already moved over to Fight Aging! - the introductory articles, topic commentaries, daily news, and so forth. In due course the Longevity Meme will close, and all traffic will be redirected to Fight Aging! Even this newsletter will become the Fight Aging! newsletter, once all of the hundred and one necessary supporting tasks are complete. The hope is that all of this packing up and moving will be seamless for you folk, and so far that seems to be working as planned.

Along the way, I would like to redesign Fight Aging!, as incorporating the main menu and content from the Longevity Meme is making the current design show both its age and lack of sophistication. I am no designer, so if anyone knows of a resource who could volunteer a good site design, please do point them in my direction.


We will soon be entering the era in which money can buy significant amounts of additional healthy life. Saving for later years has never been more beneficial than it is now, and that benefit will grow rapidly.


"Not so far down the road are organs grown to match our needs, stem cell transplants that heal our age-damaged tissues from within, artificial cells and engineered bacteria that scour our bodies for the waste products of metabolism that build up to harmful levels in the old. Beyond that even more impressive medical advances await: artificial immune systems, far better than the real thing, the complete implementation of the SENS program for rejuvenation medicine, and the dawn of the age of molecular manufacturing - everything you might need, from drugs to bioimplants, built atom by atom in desktop nanoforge machines. Which brings us to [an important point]: the utility of money is going to rise with advances in biotechnology. Some extra tens or hundreds of thousands of dollars set aside for medical expenses might save your life.

"Whatever resources you have saved up today are growing more and more valuable with time - far more than their present market value would imply - because we are entering the age in which you can use saved resources to buy additional healthy life. With each passing year the amount of additional healthy life you could purchase increases. While that yearly increase is comparatively gentle now, and the amount of extra life very modest, both will become much, much larger ten years or twenty years from now."


It is no longer remarkable that a wide range of animals can be made to live longer in good health through a wide range of methods:


"When nematode worms were first engineered to live significantly longer in good health, not very many years ago, it was a big deal. Today, few people beyond the life science community take much notice of each new study to result in a way to extend life in lower animals. Today I briefly scanned through the latest aging research papers referenced by PubMed and saw three separate reports of aging slowed in nematodes and flies, all published in just the past week or so. So the world turns: the remarkable becomes unremarkable. This is where we'd like to be with human engineered longevity - for it to be an unexciting topic, well-studied, with the work of commercial development well underway, and everyone taking it for granted that healthy lifespan will be made much longer through medical science. We're not there yet, evidently."


"A wealth of long-lived mammals can be found in the laboratories of aging researchers. The healthy life spans of these animals are extended by comparatively minor genetic alterations, drugs such as rapamycin, or environmental changes like calorie restriction that are used to identify targets for future genetic engineering. This is the domain of the metabolic engineers, who see no better way forward than to gently slow aging by tweaking the operation of human metabolism. It will be a long and expensive road, and at the end will not produce results that can help people who are already old. Metabolic engineering cannot produce rejuvenation, the reversal of aging - yet it is the dominant body of longevity science in this day and age."

Which is too bad. We would like to see a greater focus on the repair and reversal of aging, such as through realization of SENS, the strategies for engineered negligible senescence. You can learn more about that at Fight Aging!:



What more important job could there be than helping to repair the damage of aging, and thereby work towards preventing the more than 100,000 deaths by aging that occur each and every day? In the way of a recent large donation, the SENS Foundation is hiring for a research assistant position in California:


"They are looking for mitochondrial research experience because the MitoSENS project is forging ahead. The goal of this line of work is to duplicate vulnerable mitochondrial genes in the cell nucleus, while enabling the vital proteins they produce to make their way back to the mitochondria. Thus even if the genes become damaged in the mitochondria, there will be a backup source of proteins to avoid the normal consequences of mitochondrial DNA damage. ... For over 30 years mutations in mitochondrial DNA have been suspected to be important contributors to aging. If we can incorporate working copies of that mtDNA into our nuclear DNA, the mtDNA will be rendered superfluous and any mutations it suffers will be inconsequential."


Northern California is home to a fair-sized contingent of biogerontologists and several important aging research laboratories, hence the existence of the Bay Area Aging Meetings. Science blog Ouroboros provided coverage of the latest meeting, held earlier this month:


"If aging is an engineering problem, then we should be able to solve the engineering challenges more easily in simple systems. By introducing genes from a long-lived organism into the genome of a short-lived organism, it should be possible to add pro-longevity functions - in effect 'upgrading' the short-lived animal so that it lives longer. Sagi has set out to do just that, by transferring genes from the long-lived zebrafish (4-year lifespan) to the short-lived worm (4-week lifespan). ... The next obvious question: Can 'upgrade' genes be combined to further increase lifespan? Indeed they can: several pairwise combinations of genes combined to extend lifespan longer than either single gene alone. At some point it worked a little too well: the lifespan of the worms started getting long enough that the survival curves became unwieldy."


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!



Friday, December 17, 2010
Fifteen years ago, this paper or one with similar sentiments wouldn't have been accepted for publication - or if it had, it would have achieved nothing but harming the funding prospects of its author. The aging research community has only recently emerged from an era of self-censorship on the topic of engineering greater human longevity, and a field whose members do not talk about achieving a given goal will certainly make no progress towards that goal. From the abstract: "Although we do not know everything about aging, we now know enough to start its pharmacologic suppression using clinically approved drugs. Aging turns out to be driven by sensing-signaling pathways (such as the mTOR pathway). Given that some inhibitors of the mTOR pathway are already in clinical use, there is a unique opportunity to suppress aging, while treating and preventing diseases. By itself this will answer some burning questions in gerontology. Here I discuss a proposal, starting from retrospective clinical studies to animal and cellular models to drug screens in order to develop non-toxic and effective schedules and drug combinations for extending healthy life span in our lifetime." This is representative of the more eager members of the mainstream of biogerontology, focused on slowing aging through metabolic manipulation.

Friday, December 17, 2010
From Maria Konovalenko: "Melanie Swan, MBA, is an Affiliate Scholar of the IEET [and] recently summarized some important themes in aging research that were discussed at the second Bay Area Aging Meeting. ... Two interesting talks concerned UCP2 (mitochondrial uncoupling protein 2) an enzyme which reduces the rate of ATP synthesis and regulates bioenergy balance. UCP2 and UCP3 have an important but not yet fully understood role in regulating ROS (reactive oxygen species) and overall metabolic function, possibly by allowing protons to enter the mitochondria without oxidative phosphorylation. The mechanism was explored in results that worm lifespan was extended by inserting zebrafish UCP2 genes (not natively present in the worm) ... Two talks addressed the issue of immune system compromise. One team created a predictive analysis that could be used to assess an individual's immune profile and potential response to vaccines by evaluating demographics, chronic infection status, gene expression data, cytokine levels, and cell subset function. Other work looked into the specific mechanisms that may degrade immune systems in older organisms. ... Aging and other biological processes become more complicated with progression up the chain of model organisms. What works in yeast and worms may not work in mice, and what works in mice and rats may not work in humans. Some interesting research looked at ribosomal proteins, whose deletion is known to extend lifespan in model organisms. The key points were [that] there was fairly little (perhaps less than 20%) overlap in lifespan-extending ribosomal protein deletions conserved between yeast and worms."

Thursday, December 16, 2010
From the Methuselah Foundation Blog, a message from founder and CEO Dave Gobel: "It has been a while since I sent you an update and there is plenty of good news to share as we work together towards longevity. I also want your input as we make plans for the coming year. ... Methuselah Foundation has successfully promoted the extension of healthy human life - the science of aging has gained acceptance and broad-based support thanks to your ongoing contributions. Now we are strongly supporting science that will lead to tissue engineering and organ regeneration. We will be the catalyst to speed up the development of organ replacement. ... I am continually delving into every area of science, the work being done in universities, labs and biotech companies, to see the latest research and how it might contribute to longer life. I am convinced that there are many viable solutions but we, uniquely, are in a position to move them to a practical place. With this mission in mind we created the NewOrgan Prize. Based on our success with the Mprize, we anticipate this new prize will accelerate the rate of research and bring us closer to practical solutions. ... We must continue to accelerate practical scientific solutions related to aging. You and I - not just our children and grandchildren - should benefit from the advances in tissue engineering that are already on the table. This is why I need your input. We are contemplating a number of initiatives in support of this drive but we want to have the greatest possible impact. I would appreciate your thoughts and suggestions. Please continue reading and I believe you will have a clear understanding of the potential and, hopefully, will have some thoughts to share." Head on over to read the rest of the post: if you have opinions and good ideas, send them to the Foundation."

Thursday, December 16, 2010
I'd neglected to mention that the Methuselah Foundation newsletter for November was posted a couple of weeks ago: "A year ago Methuselah Foundation presented a special Mprize Lifespan Achievement Award to Z. Dave Sharp for his work with rapamycin. By the end of the year Science, Nature and TIME magazines each featured rapamycin - an antibiotic used in transplant patients that extended the life span of aged mice - as one of the most significant and exciting scientific breakthroughs of 2009. At our 2009 presentation at the Friar's Club in New York City, Dave told us a funny (after the fact) story about how the experiment ended up being done on old mice. Basically, by the time they figured out how to sneak the rapamycin into the mice food, the mice had gotten old. But three labs were on stand-by, set to start so they proceeded - making the results all the more remarkable. Rapamycin reversed aging! Now Dave has informed us that a second entire replication of the life span study has been repeated with the same results. This time the mice started taking rapamycin at nine months of age. That makes a total of SIX independent replications of the experiment!" The newsletter also provides updates on several of the Foundation's present projects and investments, such as organ printing startup Organovo.

Wednesday, December 15, 2010
Many of the conditions that occur with age might be considered exaggerated forms of "normal" aging - one aspect of damage that has raced ahead in that person for some reason. In Parkinson's disease, this damage takes the form of a decline in dopamine-secreting cells in the brain. That happens to all people to some degree, but Parkinson's sufferers have a much greater loss of these vital cells. Here researchers demonstrate that a treatment for Parkinson's produces benefits for the same symptoms seen to a lesser degree in "normal" aging: "We wished to determine whether L-DOPA, a common treatment for the motor deficits in Parkinson's disease, could also reverse the motor deficits that occur during aging. We assessed motor performance in young (2-3 months) and old (20-21 months) male C57BL/6 mice using the challenge beam and cylinder tests. Prior to testing, mice were treated with L-DOPA or vehicle. Following testing, striatal tissue was analyzed for phenotypic markers of dopamine neurons: dopamine, dopamine transporter, and tyrosine hydroxylase. Although the dopaminergic markers were unchanged with age or L-DOPA treatment, L-DOPA reversed the motor deficits in the old animals such that their motor coordination was that of a young mice. These findings suggest that some of the locomotor deficits that accompany normal aging are responsive to L-DOPA treatment and may be due to subtle alterations in dopaminergic signaling."

Wednesday, December 15, 2010
More intelligent people live longer - and we could propose all sorts of mundane and obvious reasons as to why this is the case, such as a greater and more effective use of health knowledge and medical resources. Here, a researcher proposes that there is in fact a biological reason as well: "Intelligent people live longer - the correlation is as strong as that between smoking and premature death. But the reason is not fully understood. Beyond simply making wiser choices in life, these people also may have biology working in their favor. Now research in honeybees offers evidence that learning ability is indeed linked with a general capacity to withstand one of the rigors of aging - namely, oxidative stress. Ian Deary, a psychologist at the University of Edinburgh, has proposed the term 'system integrity' for the possible biological link between intelligence and long life: in his conception, a well-wired system not only performs better on mental tests but is less susceptible to environmental onslaughts. Gro Amdam of Arizona State University and the Norwegian University of Life Sciences was intrigued by the idea and last year devised a way to test it in bees. ... Amdam hypothesizes that the ability to handle stress could be a component of system integrity; better overall stress resilience may contribute to both higher IQ scores and longer life. And if scientists can unravel what underlies these biological differences, they might be able to alleviate inborn disparities."

Tuesday, December 14, 2010
Another set of potential human longevity genes, this time associated with immune system function, and from a Russian study: "The research was aimed at studying molecular genetics basis of human longevity. The genotyping of polymorphisms in genes of interleukins 6, 10, 12, and tumor necrosis factor-alpha from ethnically homogeneous population (Tatars from Bashkortostan Republic) has been carried out. Distributions of allele and genotypes frequencies in different age groups including old men and long-livers have been characterized. Associations have been revealed between age and -627C>A polymorphism of IL-10 gene in men, -572G>C polymorphism of IL-6 gene and -308G>A polymorphism of TNF-alpha gene in women. As a whole the data obtained by us confirm the assumption that polymorphism of cytokine genes can influence on human lifespan." All of these items are associated with the correct functioning of the immune system, and are already targets for drug development in the treatment of autoimmune disorders such rheumatoid arthritis, in which the immune system has become disarrayed and malfunctioning. We should expect to see statistically significant associations between human longevity and gene variants that improve the function and resilience of the most important bodily systems.

Tuesday, December 14, 2010
News of research with potentially broad application, given the degree to which immune system damage contributes to age-related frailty: researchers "have discovered that the human body can create its own vaccine, which boosts the immune system and helps prevent chronic inflammatory diseases. ... When administered in the form of a therapeutic vaccine it is able to effectively prevent and treat a number of different inflammatory disease models for multiple sclerosis (MS), rheumatoid arthritis (RA), skin hypersensitivity and allergic asthma (AA). ... The implications of the findings are large as they shed light on an important way that the body combats inflammation and autoimmunity. Moreover, they establish a therapeutic approach for using the newly discovered protein as a treatment for multiple conditions. ... Many inflammatory and autoimmune diseases are chronic and affect a large majority of people. Moreover, there is an inflammatory component to many common diseases, such as Alzheimer's, Parkinson's, RA, AA, MS, type II diabetes and cancers. The vaccine discovered by the researchers boosts special cells of the immune system, called NKT cells. ... NKT cells are a type of T cell that exert profound and diverse regulatory effects in disease, from autoimmunity to responses to pathogens and cancer. For over two decades since their discovery NKT cells have traditionally been considered to be activated by lipid antigens presented by CD1 molecules. However, Professor Issazadeh-Navikas' group was able to show for the first time the ability of a self peptide to activate NKT cells to suppress many tissue-specific inflammatory conditions including experimental autoimmune diseases."

Monday, December 13, 2010
More progress from the tissue engineers: "For the first time, scientists have created functioning human intestinal tissue in the laboratory from pluripotent stem cells. ... their findings will open the door to unprecedented studies of human intestinal development, function and disease. The process is also a significant step toward generating intestinal tissue for transplantation, researchers say. ... This is the first study to demonstrate that human pluripotent stem cells in a petri dish can be instructed to efficiently form human tissue with three-dimensional architecture and cellular composition remarkably similar to intestinal tissue. The hope is that our ability to turn stem cells into intestinal tissue will eventually be therapeutically beneficial for people with diseases such as necrotizing enterocolitis, inflammatory bowel disease and short bowel syndromes. ... To turn pluripotent stem cells into intestinal tissue, scientists performed a timed series of cell manipulations using chemicals and proteins called growth factors to mimic embryonic intestinal development in the laboratory. The first step turned pluripotent stem cells into an embryonic cell type called definitive endoderm, which gives rise to the lining of the esophagus, stomach and intestines as well as the lungs, pancreas and liver. Next, endoderm cells were instructed to become one those organ cell types, specifically embryonic intestinal cells called a 'hindgut progenitors'. The researchers then subjected the cells to what they describe as a 'pro-intestinal' cell culture system that promoted intestinal growth. Within 28 days, these steps resulted in the formation of three-dimensional tissue resembling fetal intestine that contained all the major intestinal cell types - including enterocytes, goblet, Paneth and enteroendocrine cells. The tissue continued to mature and acquire both the absorptive and secretory functionality of normal human intestinal tissues and also formed intestine-specific stem cells."

Monday, December 13, 2010
Here is an example from Discovery News of one way in which popular science articles fall down: by focusing too closely on the research immediately to hand and failing to present the wider context. This article looks at the effect of damaging free radicals on life span in laboratory animals, but fails to talk in any detail about the range of research on hormesis effects: "Conventional wisdom has held for decades that free radicals cause aging, and that antioxidants, which squelch the reactivity of these highly reactive molecules, are a way to slow the process. But new work adds to a growing body of research that suggests the story is not so simple. In the new study published in PLoS Biology, worms that made more free radicals or that were treated with a free-radical-producing herbicide actually lived longer than normal worms. What's more, when the longer-lived mutant worms were given antioxidants, the effects were reversed, and the worms had a conventional worm lifespan. The finding flies in the face of the idea that antioxidants battle the effects of aging. ... what is emerging from this and other experiments is a view of free radicals - or, more precisely, reactive oxygen species - as a normal part of the body's stress response, with beneficial effects at certain levels."



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