Longevity Meme Newsletter, September 27 2010

LONGEVITY MEME NEWSLETTER
September 27 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.

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CONTENTS

- SENS Foundation Funds TTR Amyloidosis Research
- Third SENS Foundation Los Angeles Chapter Meeting
- Informed Skepticism Versus Uninformed Skepticism
- On Changing the Name of the Longevity Meme
- Discussion
- Latest Healthy Life Extension Headlines

SENS FOUNDATION FUNDS TTR AMYLOIDOSIS RESEARCH

TTR Amyloidosis is the condition discovered to cause the death of supercentenarians, people who live to a great age by avoiding or surviving all other age-related diseases. The SENS Foundation recently funded a research program to develop a therapy to reverse it:

https://www.fightaging.org/archives/2010/09/sens-foundation-funds-research-into-a-therapy-for-ttr-amyloidosis.php

"TTR is a protein that cradles the thyroid hormone thyroxine and whisks it around the body. In TTR Amyloidosis, the protein amasses in and clogs blood vessels, forcing the heart to work harder and eventually fail. 'The same thing that happens in the pipes of an old house happens in your blood vessels' ... This is one of many types of amyloid that build up in the body with age. If we want to repair the damage of aging, we'll have to learn how to remove these unwanted substances - and certainly find ways to reverse the course of TTR amyloidosis, which at present looks very much like the roadblock at the end of life.

"The first phase of the research is funded to the tune of $150,000, and will involve the development of antibodies that can safely break down TTR amyloid and thus render it harmless. ... TTR-based senile cardiac amyloidosis is an underdiagnosed and heretofore-untreatable disease that is prevalent in the aging population and poised to become a widespread medical problem with the aging of the global population and the improved treatment of more familiar age-related diseases."

THIRD SENS FOUNDATION LOS ANGELES CHAPTER MEETING

If you're in the Los Angeles area, you might consider dropping by:

https://www.fightaging.org/archives/2010/09/third-sens-foundation-los-angeles-chapter-meeting.php

"On behalf of SENS Foundation I am thrilled to write to you to invite you to join Dr. Aubrey De Grey, Dr. Sarah Marr, Dr. L. Stephen Coles, and actor/director Edward James Olmos for our third SENS Foundation L.A. Chapter meeting to be held on Saturday, October 2, 2010. ... We've put together a spectacular program for this third meeting beginning with a presentation by Dr. L. Stephen Coles (Director of the Gerontology Research Group and the Supercentenarian Research Foundation) who will give us an update on DNA Sequencing in Human Supercentenarians, starting at 5:00 PM. Following this, at around 6:30 PM, Aubrey (SENS Foundation Co-founder and CSO) and Sarah (SENS Foundation Co-founder and Executive VP) will talk about the Foundation's work and recent developments in the field, and Edward James Olmos will say a few words to our guests. ... please RSPV."

INFORMED SKEPTICISM VERSUS UNINFORMED SKEPTICISM

As the future continues to arrive, year after year, it will become ever harder to tell the difference between "anti-aging" frauds and real, legitimate longevity science:

https://www.fightaging.org/archives/2010/09/informed-skepticism-versus-uninformed-skepticism.php

"As rules go, 'ignore anyone who says you can alter aging by sticking novel things in your mouth and swallowing' is a good one. The world is full of fools selling false hope to idiots, and most of this nonsense takes the form of pills, potions, and recommendations to gorge only on specific types of food. We are an orally fixed culture when it comes to anti-aging flim-flam. Had I more time, I might speculate on the deep mythological roots of this sort of thing: modern hucksterism as a direct descendant of shamanic magical thinking, drawing on core aspects of the human condition to weave a web of make-believe.

"But one doesn't have to go much further than pointing out that some people are greedy and inventive, while others are gullible - or at least not paying as much attention to a given topic as they might. That is sufficient to explain much of what we see around us: if selling a $1 lump of fool's gold for $20, all you really have to do is ensure that you're selling in a place and time where it costs much more than $20 (in time or money) to fully understand the transaction. Biology is fearsomely complex, and few people are prepared to put in the time required to understand whether or not the claims made for a particular purchase or recommendation are nonsense - and the answer is rarely as simple as 'yes' or 'no.'"

ON CHANGING THE NAME OF THE LONGEVITY MEME

Yes, I am considering a name change:

https://www.fightaging.org/archives/2010/09/on-changing-the-name-of-the-longevity-meme.php

"Across the near-decade of running the Longevity Meme as a resource for folk interested in healthy life extension and the science of engineering greater human longevity, a great many people have suggested that I change the name. A good name for any sort of non-profit, service-oriented, or advocacy initiative is distinctive, unambiguous, and points directly towards the initiative's goals and associations. By those standards, 'Fight Aging!' is a good name. 'The Longevity Meme,' not so good. The main problem with the name, as I am continually reminded, is that 95% of the populace are unfamiliar with the word 'meme.'

"None of which is to say that I have a new name in mind, a timeline for making this change, or that I am expecting any great bolt of inspiration to strike from the blue. But there are plenty of options regardless. I could, for example, roll the Longevity Meme into the Fight Aging! brand as 'Fight Aging! News.' Or keep 'Longevity' - for search engine optimization and continuity reasons - and find some new longevity-related title that captures the meaning of the old but is more straightforward. Suggestions are welcome."

DISCUSSION

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!

Reason

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LATEST HEALTHY LIFE EXTENSION HEADLINES

POTASSIUM CHANNELS AS BIOMARKER FOR LONGEVITY (September 24 2010)
https://www.fightaging.org/archives/2010/09/potassium-channels-as-biomarker-for-longevity/
Sooner or later, researchers will turn up good biomarkers for aging and longevity - tools that are needed to properly evaluate therapies that aim to repair the biochemical damage of aging in humans. Here is another candidate biomarker: "Aging is a complex process resulting from, among other, dynamic non-linear interactions between genetics and environment. Centenarians are the best example of successful aging in humans, as they escaped from, or largely postponed, major age-related diseases. Ionic fluxes changes play a key role in several patho-physiological cellular processes, but their relation to human aging is largely unexplored. In the present study we have [compared] potassium (K+) current recordings from dermal fibroblasts (DF) obtained from young, elderly and centenarian donors. We found that in DF from elderly donors, but not from centenarians, K+ current amplitude is significantly smaller with respect to DF from young donors. Moreover, cell membrane capacitance of DF from elderly donors is smaller with respect to young donors and centenarians. ... The maintenance of 'young' K+ currents and the peculiar age-related remodeling of K+ channel subtypes in centenarian's DF is likely associated with successful aging and might provide a predictive marker of longevity."

THOUGHTS ON CALORIE RESTRICTION AND SENESCENT CELLS (September 24 2010)
https://www.fightaging.org/archives/2010/09/thoughts-on-calorie-restriction-and-senescent-cells/
A commentary on recent research showing calorie restriction to reduce the number of senescent cells in some tissues: "The relatively short period of caloric restriction resulted in a 3.3 to 6.5% decrease in senescent cell abundance as a function of total cell number. ... As with many interesting studies, this study raises many more questions than it answers. ... Does short term caloric restriction reduce the proportion of senescent cells in other tissues, such as fat? Obesity, aging, and other conditions are associated with extensive accumulation of senescent cells in fat tissue of rodents as well as humans ... Does short term caloric restriction also reduce abundance of senescent cells and inflammation in humans? It may not, since, as the authors point out, proliferation-competent skin fibroblasts did not increase after 9 to 12 years of caloric restriction in rhesus monkeys. On the other hand, it might, since white blood cell DNA fragmentation [declines] in overweight but non-obese adult human subjects subjected to 25% caloric restriction for 6 months ... What is the cell dynamic mechanism that causes decreased senescence during short term caloric restriction? Altered rates of senescent cell formation or removal could be responsible for the effect of short term caloric restriction on abundance of senescent cells. ... Senescent cells can be removed through activation of the immune system, with the immune system being activated by factors released by senescent cells. Short term caloric restriction could enhance immune system responsiveness to senescent cells, a possibility that remains to be tested."

THE FUTURE OF CIRM (September 23 2010)
https://www.fightaging.org/archives/2010/09/the-future-of-cirm/
This San Franscisco Business Times article looks at the future of the California Institute for Regenerative Medicine (CIRM): "The architect of Proposition 71 - the 2004 voter-approved measure that set up California's stem cell research funding agency with $3 billion in state-backed bond financing - says the California Institute for Regenerative Medicine by 2016 could seek another $3 billion to $5 billion. That may seem like a tough sell in a state smacked upside the head by a recession, but Klein is the ultimate salesman / evangelizer / patient advocate. He pulled together a powerful group of people cutting across political party lines and backgrounds to get Prop. 71 passed when most people had no scientific concept of stem cells. Strategically, what we're focused on is trying to make sure there is enough therapies advanced to Phase I or Phase II efficacy trials (where) voters of California can judge the performance and decide if they should approve another $3 billion to $5 billion. The voters are going to have to see real evidence. ... But wasn't CIRM limited to a 10-year life? No, Klein said - Prop. 71 backers simply estimated that funding would not be spent any faster than 10 years. Legal challenges delayed that another two years, he said, so funding likely won't be exhausted until late 2016 or early 2017. By then, Klein said, many clinical trials will be well under way."

AN INTERVIEW WITH JONATHAN WEINER (September 23 2010)
https://www.fightaging.org/archives/2010/09/an-interview-with-jonathan-weiner/
Reason Magazine interviews the author of Long for this World: "The field [of longevity research] is really badly underfunded. Even the National Institute of Aging spends a fraction of its budget on experimental gerontology. Most of the budget of the National Institutes of Health goes for fighting recognized diseases and it's much more acceptable politically to declare war on cancer than to declare war on aging. So if you want to study aging and dream of slowing it down, you've got a tough time getting funding. That worries me more now having finished the book and having spent so much time talking with the gerontology mainstream as well as Aubrey [de Grey]. We may be missing really wonderful opportunities by neglecting the sciences of aging, for instance all of those late onset diseases, not just cancer, Alzheimer's, diabetes, atherosclerosis, all of those late onset diseases become more likely [as we age]. If we want to fight cancer, the most plausible research direction may be to understand those small invisible steps leading us there. Likewise with Alzheimer's, diabetes, it may not be there is a different story with each. It may be there are common problems which we might be able to address and if we could, suddenly what sounds so futuristic and strange now might become as pedestrian and common sensical as preventive medicine. If we would just be doing the equivalent of taking out garbage, flossing the teeth, doing standard maintenance work for the body in our prime, that could postpone or even prevent disease entirely."

LONG LIVED HUMANS RESISTANT TO CYTOMEGALOVIRUS (September 22 2010)
https://www.fightaging.org/archives/2010/09/long-lived-humans-resistant-to-cytomegalovirus/
Cytomegalovirus is one of the important contributions to immune system failure with aging: most people are infected, and it causes an ever-greater fraction of available T cells to be uselessly specialized to fight it, leaving too few naive T cells left for other jobs. Intriguingly, it seems that long-lived people have some resistance to this consequence of infection: "we analyzed long-lived families in the Leiden Longevity Study (LLS) in which offspring enjoy a 30% reduced standardized mortality rate, possibly owing to genetic enrichment. We [determined] the capacity of T cells to respond [against] CMV in a smaller group of LLS subjects and controls. CMV infection was strongly associated with an age-related reduction in the frequency of naive T cells and an accumulation [of] late-differentiated effector memory T cells in the general population, but not in members of long-lived families. The latter also had significantly lower C-reactive protein levels, indicating a lower proinflammatory status compared with CMV-infected controls. ... Our data suggest that these rare individuals genetically enriched for longevity are less susceptible to the characteristic CMV-associated age-driven immune alterations commonly considered to be hallmarks of immunosenescence, which might reflect better immunological control of the virus and contribute to their decreased mortality rate." Hopefully the basis for this resistance can be uncovered and made into a therapy.

WERNER SYNDROME GENE DECLINES WITH AGING (September 22 2010)
https://www.fightaging.org/archives/2010/09/werner-syndrome-gene-declines-with-aging/
Mutation of the WRN gene causes the accelerated aging condition Werner Syndrome. Absence of the correctly formed protein encoded by the gene impairs DNA repair, which in turn leads to the symptoms of accelerated aging. But as this research shows, gene expression of WRN appears to decline with "normal" aging as well: "The WRN gene encodes DNA helicase participating in genome maintenance. We looked for associations of natural aging with expression and methylation of this gene in blood mononuclear cells and with its common polymorphisms. Analyses were performed in ethnically homogenous Polish Caucasians. The mean level of the WRN messenger RNA was significantly lower in long-living individuals than in young and middle-aged controls. Analysis [showed] that aging might be accompanied by a slight increase of its methylation status; however, it seems to be biologically insignificant. Finally, analysis [showed] that the frequencies of the L1074F and C1367R polymorphisms were similar in all age groups tested ... We suggest that age-related decrease of the WRN expression but not its common genetic variants might contribute to human immunosenescence."

THE REPRODUCTIVE-CELL CYCLE THEORY OF AGING (September 21 2010)
https://www.fightaging.org/archives/2010/09/the-reproductive-cell-cycle-theory-of-aging/
There is no shortage of theories of aging: "The Reproductive-Cell Cycle Theory posits that the hormones that regulate reproduction act in an antagonistic pleiotrophic manner to control aging via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence. ... The theory is able to explain: 1) the simultaneous regulation of the rate of aging and reproduction as evidenced by the fact that environmental conditions and experimental interventions known to extend longevity are associated with decreased reproductive-cell cycle signaling factors, thereby slowing aging and preserving fertility in a hostile reproductive environment; 2) two phenomena that are closely related to species lifespan - the rate of growth and development and the ultimate size of the animal; 3) the apparent paradox that size is directly proportional to lifespan and inversely proportional to fertility between species but vice versa within a species; 4) how differing rates of reproduction between species is associated with differences in their lifespan; 5) why we develop age-related diseases; and 6) an evolutionarily credible reason for why and how aging occurs - these hormones act in an antagonistic pleiotrophic manner via cell cycle signaling; promoting growth and development early in life in order to achieve reproduction, but later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence."

THE COST OF DEMENTIA (September 21 2010)
https://www.fightaging.org/archives/2010/09/the-cost-of-dementia/
Via EurekAlert!: "Alzheimer's disease and other dementias are exacting a massive toll on the global economy, with the problem set to accelerate in coming years. ... The worldwide costs of dementia will exceed 1% of global GDP in 2010, at US$604 billion. ... The scale of this crisis cries out for global action. History shows that major diseases can be made manageable - and even preventable - with sufficient global awareness and the political will to make substantial investments in research and care options." We see arguments for investment in research based upon the cost of inaction for all the major diseases of aging - but a distinct lack of effort in the mainstream to present the same argument for aging itself, the basis for all these diseases. The cost of degenerative aging is far, far greater than any natural disaster, war, or other medical condition. Yet at the very same time as people are prepared to listen to and be motivated by the cost of all these other horrors, aging isn't considered. This is one of the many puzzles surrounding the way in which the realities of aging and the potential for medical science to do something about it are widely ignored.

SEARCHING FOR CANCER STEM CELLS (September 20 2010)
https://www.fightaging.org/archives/2010/09/searching-for-cancer-stem-cells/
The search for ways to identify cancer stem cells is a subset of the broader search for commonalities in cancer: any biochemical similarity in cancer cells that marks them as different from normal cells is a potential opening for a targeted therapy. Here is an example of the sort of investigations presently taking place: "Despite many years of intensive effort, there is surprisingly little consensus on the most suitable markers with which to locate and isolate stem cells from adult tissues. By comparison, the study of cancer stem cells is still in its infancy; so, unsurprisingly, there is great uncertainty as to the identity of these cells. ... This review assesses the utility of recognizing cancer stem cells by virtue of high expression of aldehyde dehydrogenases (ALDHs), probably significant determinants of cell survival through their ability to detoxify many potentially cytotoxic molecules, and contributing to drug resistance. Antibodies are available against the ALDH enzyme family, but the vast majority of studies have used cell sorting techniques to enrich for cells expressing these enzymes. ... For many human tumours, but notably breast cancer, cell selection based upon ALDH activity appears to be a useful marker for enriching for cells with tumour-initiating activity (presumed cancer stem cells)."

CANCER IMMUNOTHERAPY AND NANOMEDICINE (September 20 2010)
https://www.fightaging.org/archives/2010/09/cancer-immunotherapy-and-nanomedicine/
A review paper: "The immune system has the ability to recognize and kill pre-cancer and cancer cells. However, with the immune system's surveillance, the survival tumor cells learn how to escape the immune system after immunoselection. Cancer immunotherapy develops strategies to overcome these problems. Nanomedicine applications in cancer immunotherapy include the nanodiagnostics and nanobiopharmaceuticals. In cancer nanodiagnostics, it looks for specific 'molecular signatures' in cancer cells or their microenvironment by using genomics and proteomics. Nanobiopharmaceuticals is the field that studies nanotechnology-based therapeutic agents and drug carriers. DNA, RNA, peptides, proteins and small molecules can all be used as cancer therapies when formulated in nanocarriers. Currently, cancer vaccines are applied in treatments with existing cancer or to prevent the development of cancer in certain high risk individuals. Most of the non-specific immune activation agents include adjuvants which enhance immunogenicity and accelerate and prolong the response of cancer vaccines. The carriers of vaccines, such as viruses and nanoparticles, have also been in clinical studies for many years."

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