Fight Aging! Newsletter, February 27th 2012

February 27th 2012

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!



- The Weight of the Inheritors
- Aubrey de Grey and Max More at BIL in March
- On Telomeres and Longevity
- Stem Cell Transplant Extends Mouse Life Span
- Stem Cell Medicine Must Ultimately Address Aging
- Discussion
- Latest Headlines from Fight Aging!


Thoughts on obligation and the plausible future:

"The visible future is by any sensible measure nothing less than science fiction. Any given snapshot of that future is made up of countless trillions of ageless humans, sophisticated machine intelligences, and yet to be categorized hybrids of the two, spread throughout the solar system in palatial standards of living, and beginning to drift beyond to the nearby stars - a vast thistledown of intelligence and culture, a million times greater and more diverse than today's world, just beginning its explosion into the winds. These are the Inheritors, to borrow a term from an obscure work of science fiction.

The question for today is this: to what degree are we obligated by the Inheritors? They are yet to exist, but we know that we can bring them into being, and indeed seem to be headed in that direction: there is nothing especially controversial about a future cosmopolitan solar system, or the ability to defeat aging given a sufficiently long timescale to work on the necessary biotechnology. ... From a utilitarian perspective, one could argue that creating and perpetuating intelligences possessed of free will, freedom, and opportunity is the highest aspiration, the greatest end goal for human action - turning clay into sentience, as it were. Speeding any step towards the technologies necessary for the existence of the Inheritors (enhanced longevity, control of disease, strong artificial intelligence, low cost orbital lift systems, and so forth) will ultimately bring a benefit that is measured in millions of lives - even in increments of a day here, a day there. This is time lived in aggregate: deaths prevented, additional person-days lived well per day, days of suffering eliminated, and so forth. ... But are we obligated to the future?"


The BIL unconference is imminent, and Aubrey de Grey of the SENS Foundation and Max More of Alcor will be amongst the speakers:

"This year's BIL unconference will be held on March 3rd, on the Queen Mary in Long Beach, California. ... BIL is an ad-hoc conference for people changing the world in big ways. It's a place for passionate people to come together to energize, brainstorm, and take action. ... Most of you have heard of TED or watched the talks online, but do you know about BIL, the quirky, populist, unconference taking place nearby? Open to the public and fully participant powered, BIL features a wild mix of technologists, scientists, artists, hackers, and those with a passion for community awareness."


Telomere biology is enormously complex, which is one of the reasons why the question of whether telomere shortening with age is a fundamental cause of aging is still open:

"Telomeres are the ends of the chromosome, caps of repeating DNA sequences that shorten with each cell division and lengthen according to the activity of the enzyme telomerase - this is a very dynamic process, responding differently to circumstances in different cells and tissue types. Telomere length somewhat acts as a countdown clock, moving a cell towards shutdown after a certain number of divisions rather than permitting continued replication, but as for all matters biological the telomere-telomerase-chromosome system considered as a whole is exceedingly complex. It influences and is influenced by many other important cellular systems and feedback loops: mitochondrial damage, for example, appears tied to telomere length and telomerase activity. Thus even as data rolls in ever faster in this age of biotechnology, the telomere story has stubbornly remained that telomeres generally become shorter on average with age or ill health or stress, and that this shortening might be a contribution to aging or it might only be a marker for other cellular changes and damage that occurs with aging.

"This is an important distinction to draw: we should find ways to fix and reverse the changes that are fundamental, that are causes of aging. But we don't have to fix and reverse the markers and secondary changes. If we repair the root causes, the many other line items should take care of themselves. But biology is complicated - obtaining the answers for processes that are right down there in the depths of the cellular machinery, central to everything and touching on everything, takes time."


This is not the first time that researchers have demonstrated modestly extended life in mice through transplant of stem cells, and nor is it the first time that attempts to treat osteoporosis have resulted in extended life span:

"Increasing evidence suggests that the loss of functional stem cells may be important in the aging process. Our experiments were originally aimed at testing the idea that, in the specific case of age-related osteoporosis, declining function of osteogenic precursor cells might be at least partially responsible. To test this, aging female mice were transplanted with mesenchymal stem cells from aged or young male donors. We find that transplantation of young mesenchymal stem cells significantly slows the loss of bone density and, surprisingly, prolongs the life span of old mice. These observations lend further support to the idea that age-related diminution of stem cell number or function may play a critical role in age-related loss of bone density in aging animals and may be one determinant of overall longevity.

"The mean life span of control mice was 765 days However, the mean life span for mice that received young [stem cell] transplants was 890 days ... Overall, these results suggest that transplantation of [stem cells] derived from young animals extends life span. However, it is not clear whether the prolonged lifespan may be associated with improved tissue regeneration."


The future of stem cell medicine must, eventually, incorporate rejuvenation of the stem cells and stem cell support systems in the body:

"The long term goals for the field of stem cell medicine tend to come back around to include rejuvenation at some point. It's unavoidable, really: the medical conditions most obviously suited to treatment via stem cell therapies are the malfunctions and disrepair of old age - failing muscles, hearts, livers, and other more complex organs. But stem cell populations and their supporting infrastructure in the body also fail right at the time when they are most needed. (That progressive failure of stem cell capacity with age goes some way to causing the time of greatest need, of course, but it's far from the whole story of degenerative aging). The bottom line is that to ensure effectiveness for stem cell treatments in the old, efforts must be made to reverse the aging of their stem cells and the aging of stem cell support systems in the body.

"Unlike stem cells in the blood or skin, muscle stem cells spend most of their lives nestled in the surrounding tissue. 'They don't do much most of the time,' said Rando. 'They remain in a quiescent state for most of a person's life. When you injure your muscle, however, they begin dividing to repair the damage. ... Although on the surface the quiescent state seems to be relatively static, it's quite actively maintained. We've found that changing the levels of just one specific microRNA in resting muscle stem cells, however, causes them to spring into action.'

"In the future, the researchers will continue to look at the unique features of quiescent muscle stem cells, including those involved in normal aging. 'We'd like to understand the aging process at a very fundamental level,' said Rando. 'That will allow us to move toward more therapeutic applications. Can we use what we've learned to convert old stem cells, which seem to have lost their responsiveness to activation cues, into young stem cells? Maybe the ability of old stem cells to exit the quiescent state is defective. We may one day be able to develop approaches that enhance tissue repair by enhancing stem cell function.'"


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, February 24, 2012
Philosophy determines strategy - it matters greatly which of the answers to the fundamental existential questions you subscribe to. Consider questions of identity, for example: do you identify with the pattern that is you, or do you identify with the present slowly changing collection of physical structure that is you? If the former, you might consider destructively uploading the data of your mind to a robust computing system to be a fine strategy for the defeat of aging. If the latter, destructive uploading looks like an expensive and ornate suicide method - you are not your copy, and you will not survive the procedure. Doors to the future open or close depending on your philosophical inclinations. Here's a piece that reviews some of the spectrum of philosophical thinking on identity, which has been going on for a good deal longer than modern ideas and technologies have been around: "Star Trek-style teleportation may one day become a reality. You step into the transporter, which instantly scans your body and brain, vaporizing them in the process. The information is transmitted to Mars, where it is used by the receiving station to reconstitute your body and brain exactly as they were on Earth. You then step out of the receiving station, slightly dizzy, but pleased to arrive on Mars in a few minutes, as opposed to the year it takes by old-fashioned spacecraft. But wait. Do you really step out of the receiving station on Mars? Someone just like you steps out, someone who apparently remembers stepping into the transporter on Earth a few minutes before. But perhaps this person is merely your replica - a kind of clone or copy. That would not make this person you: in Las Vegas there is a replica of the Eiffel Tower, but the Eiffel Tower is in Paris, not in Las Vegas. If the Eiffel Tower were vaporized and a replica instantly erected in Las Vegas, the Eiffel Tower would not have been transported to Las Vegas. It would have ceased to exist. And if teleportation were like that, stepping into the transporter would essentially be a covert way of committing suicide."

Friday, February 24, 2012
Via Extreme Longevity: "Progeria is a rare disease in which children age very rapidly, acquire diseases of the elderly and typically die in teenage years with the phenotypical appearance of the elderly. The disease has been found to occur due to mutations in the LMNA gene which codes for the nuclear envelope proteins called lamin-A and lamin-B. These proteins are responsible for the security and integrity of the nuclear membrane surrounding the cell's DNA. When these proteins are mutated the DNA is poorly protected and quickly and extensively damaged leading to accelerated aging. In this study the researchers hypothesized that just as certain single nucleotide polymorphisms (SNPs or mutations) cause individuals with progeria to age rapidly, perhaps other variants of the gene would protect people from aging and lead to extreme longevity. To test this hypothesis, the researchers compared 16 SNP variants of the LMNA gene in persons over age 95 versus genetically matched younger controls. They detected a specific 4-SNP variation of the gene appeared to be more frequent in the elderly. They then looked for the presence of this haplotype in several other genetic databases of centenarians and again found a higher frequency than chance of the same mutation. The authors concluded 'these results suggest that LMNA variants may play a role in human lifespan.'"

Thursday, February 23, 2012
An article on recent sirtuin research - while extended longevity is demonstrated, I don't think it changes the big picture on sirtuins all that much: "Mammals, including humans, have seven types of sirtuins, called SIRT1 to SIRT7. Scientists aren't sure what these proteins do, although there is some evidence suggesting that they might help prevent chronic diseases such as cancer and cardiovascular disease. For example, resveratrol, the nutrient found in grape skins (and red wine), has been shown to have a positive effect on heart health, and it may work by activating the SIRT1 gene to make more SIRT1 protein. The Israeli researchers, led by Yariv Kanfi, focused on SIRT6. The team's previous work revealed that mice genetically bred to have lots of SIRT6 could get fat on rich diets yet show no signs of heart disease, fatty liver disease and other diseases associated with obesity. Previous research by other groups showed that mice genetically bred to have little SIRT6 don't live very long. And, conversely, rats living longer on a calorie-restricted diet have increased levels of SIRT6 in their blood. So, this time the Israeli team simply decided to let the SIRT6 mice live a natural life. These male mice lived longer, about 16 percent longer on average, than regular mice kept in the same conditions. The female mice with the SIRT6 gene enhancement didn't live longer than regular mice. The researchers speculate that, considering how male mice have a higher rate of cancers compared with the females, the SIRT6 could be acting as a tumor suppressor and thus have a larger effect on male life span than female life span."

Thursday, February 23, 2012
A novel viewpoint is outlined in this article, though as always it remains to be seen how important the effect is in comparison with other concrete manifestations of aging: "For decades, scientists have looked for explanations as to why certain conditions occur with age, among them memory loss, slower reaction time, insomnia and even depression. They have scrupulously investigated such suspects as high cholesterol, obesity, heart disease and an inactive lifestyle. Now a fascinating body of research supports a largely unrecognized culprit: the aging of the eye. The gradual yellowing of the lens and the narrowing of the pupil that occur with age disturb the body's circadian rhythm, contributing to a range of health problems, these studies suggest. As the eyes age, less and less sunlight gets through the lens to reach key cells in the retina that regulate the body's circadian rhythm, its internal clock. ... Circadian rhythms are the cyclical hormonal and physiological processes that rally the body in the morning to tackle the day's demands and slow it down at night, allowing the body to rest and repair. This internal clock relies on light to function properly, and studies have found that people whose circadian rhythms are out of sync, like shift workers, are at greater risk for a number of ailments, including insomnia, heart disease and cancer. ... We believe that it will eventually be shown that cataract surgery results in higher levels of melatonin, and those people will be less likely to have health problems like cancer and heart disease"

Wednesday, February 22, 2012
A look at ongoing work on nerve regeneration in one laboratory: "One technology used [by] neurosurgeons is the NeuraGen Nerve Guide, a hollow, absorbable collagen tube through which nerve fibers can grow and find each other. The technology is often used to repair nerve damage over short distances less than half an inch long. ... [Researchers] compared several methods to try to bridge a nerve gap of about half an inch in rats. The team transplanted nerve cells from a different type of rat into the wound site and compared results when the NeuraGen technology was was used alone or when it was paired with [dorsal root ganglion neurons, or DRG cells], or with other cells known as Schwann cells. After four months, the team found that the tubes equipped with either DRG or Schwann cells helped bring about healthier nerves. In addition, the DRG cells provoked less unwanted attention from the immune system than the Schwann cells, which attracted twice as many macrophages and more of the immune compound interferon gamma. While both Schwann and DRG cells are known players in nerve regeneration, Schwann cells have been considered more often as potential partners in the nerve transplantation process, even though they pose considerable challenges because of the immune system's response to them. ... In a related line of research, [scientists] are creating DRG cells in the laboratory by stretching them, which coaxes them to grow about one inch every three weeks. The idea is to grow nerves several inches long in the laboratory, then transplant them into the patient, instead of waiting months after surgery for the nerve endings to travel that distance within the patient to ultimately hook up."

Wednesday, February 22, 2012
From the Methuselah Foundation blog: "A thin layer of human skeletal muscle is being printed by Chirag Khatiwala in a small, sterile room of San Diego-based startup Organovo. Each muscle cell from the company's signature 3-D printer is uniformly deposited in closely spaced lines on a petri dish. This allows the cells to grow and interconnect until they form working muscle tissue nearly indistinguishable from a human muscle biopsy. Unlike other experimental approaches that utilize ink-jet printers to deposit cells, Organovo's technology enables cells to interact with each other the way they do in the body. How? They are packed tightly together, sandwiched, if you will, and incubated. This prompts them to cleave to each other and interchange chemical signals. When printed, the cells are grouped together in a paste that helps them grow, migrate, and align themselves properly. In the case of muscle cells, the way they orient themselves in the same direction allow for contractions of the tissue. ... Methuselah Foundation honors the efforts of Organovo through early funding and support as well as through its new, highly anticipated New Organ Mprize. The true prize is elevated health and quality of life for those that have had to or will suffer the blows of a failing organ. Every $10 helps us work in tandem with today's stunningly advanced technology so that at some tomorrow, no one will have to suffer or die because of a diseased organ."

Tuesday, February 21, 2012
The latest issue of the Cryonics magazine is available online in PDF format: "The January-February 2012 issue of Cryonics marks the return of Alcor's magazine as a bi-monthly professionally printed publication. This issue features two major articles on cryonics and brain-threatening disorders. The first article, by Cryonics editor Aschwin de Wolf, provides a framework for thinking about identity-destroying brain diseases and discusses what Alcor members can do to prevent them from threatening your cryopreservation. Alcor staff member Mike Perry returns to the topic of brain-threatening disorders and presents his updated findings on the options available to cryonicists who have been diagnosed with such a disease, (like Alzheimer's). After being CEO at Alcor for one year, Alcor CEO and President Max More reflects on his Alcor experience to date and we get a look into the interesting career of one of the pioneers of transhumanism. Another Alcor veteran, Russel Cheney, contributes an article about the importance of 'superfunding' your cryopreservation arrangements."

Tuesday, February 21, 2012
Via the Guardian: "Fasting for regular periods could help protect the brain against degenerative illnesses ... Researchers [had] found evidence which shows that periods of stopping virtually all food intake for one or two days a week could protect the brain against some of the worst effects of Alzheimer's, Parkinson's and other ailments. ... Reducing your calorie intake could help your brain, but doing so by cutting your intake of food is not likely to be the best method of triggering this protection. It is likely to be better to go on intermittent bouts of fasting, in which you eat hardly anything at all, and then have periods when you eat as much as you want. In other words, timing appears to be a crucial element to this process. ... have also worked out a specific mechanism by which the growth of neurons in the brain could be affected by reduced energy intakes. Amounts of two cellular messaging chemicals are boosted when calorie intake is sharply reduced. ... These chemical messengers play an important role in boosting the growth of neurons in the brain, a process that would counteract the impact of Alzheimer's and Parkinson's. ... The cells of the brain are put under mild stress that is analogous to the effects of exercise on muscle cells. The overall effect is beneficial. ... The link between reductions in energy intake and the boosting of cell growth in the brain might seem an unlikely one, but [there are] sound evolutionary reasons for believing it to be the case. ... When resources became scarce, our ancestors would have had to scrounge for food. Those whose brains responded best - who remembered where promising sources could be found or recalled how to avoid predators - would have been the ones who got the food. Thus a mechanism linking periods of starvation to neural growth would have evolved." You might recall that intermittent fasting and straight calorie restriction depend on different sets of genes in mice, suggesting that they are not working to enhance health in the same ways - this latest research tends to reinforce that view.

Monday, February 20, 2012
The present state of research in the accelerated aging condition progeria shows it to result from malformed proteins important to the structure of the cell nucleus - which is something that also occurs in normal aging, but to a much lesser degree. Here is a look at what some researchers are doing with this information - producing the tools needed to get to the next step in their investigations: "The premature aging disorder, Hutchinson-Gilford progeria syndrome (HGPS), is caused by mutant lamin A, which affects the nuclear scaffolding. The phenotypic hallmark of HGPS is nuclear blebbing. Interestingly, similar nuclear blebbing has also been observed in aged cells from healthy individuals. Recent work has shown that treatment with rapamycin, an inhibitor of the mTOR pathway, reduced nuclear blebbing in HGPS fibroblasts. However, the extent of blebbing varies considerably within each cell population, which makes manual blind counting challenging and subjective. Here, we show a novel, automated and high throughput nuclear shape analysis that quantitatively measures curvature, area, perimeter, eccentricity and additional metrics of nuclear morphology for large populations of cells. We examined HGPS fibroblast cells treated with rapamycin and RAD001 (an analog to rapamycin). Our analysis shows that treatment with RAD001 and rapamycin reduces nuclear blebbing, consistent with blind counting controls. In addition, we find that rapamycin treatment reduces the area of the nucleus, but leaves the eccentricity unchanged. Our nuclear shape analysis provides an unbiased, multidimensional 'fingerprint' for a population of cells, which can be used to quantify treatment efficacy and analyze cellular aging."

Monday, February 20, 2012
You may recall that levels of high-density lipoproteins (HDL) have been shown to correlate with human longevity, such as in centenarian studies. Here is another very long term study that also shows an association, using a "fifty-three-year prospective follow-up of Gofman's Livermore Cohort between 1954 and 2008. ... One thousand one hundred forty-four men who consented to the study, had analytic ultracentrifuge measurements of lipoprotein subfractions at baseline, and were old enough at baseline to have survived to age 85 during follow-up. ... Three hundred ninety men survived to 85 years old (34.1%). Survivors were less likely than nonsurvivors to be in the lowest HDL3 and HDL2 quartiles. Logistic regression analyses showed that the lowest HDL3 quartile significantly predicted shorter longevity. ... Men who were above the 25th HDL3 percentile had 70% greater odds of surviving until age 85 than those below this level, which persisted when adjusted for HDL2, very low-density lipoprotein (LDL), and standard risk factors. Proportional hazard analyses of survival before age 85 showed that being in the lowest HDL3 quartile increased age-adjusted cancer risk by 39% and noncancer risk by 23% when adjusted for other risk factors."



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