Longevity Meme Newsletter, August 09 2010
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August 09 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.



- Twenty Minutes to Justify Longevity Science
- Regeneration as Controlled Cancer
- Blood, as Needed
- Until We Stand Restored
- Discussion
- Latest Healthy Life Extension Headlines


Over at Fight Aging!, a commenter recently asked "If you only had 20 minutes, what would you do to convince an intelligent (college educated or professional) audience [that] extreme life extension is scientifically valid research?" In response, I pulled together a quick draft outline for a presentation, which is linked below:


You're all welcome to improve, refine, and redistribute it, if so inclined.


The manifold biological processes involved in regeneration, embryonic growth, and cancer share a great many similarities. As researchers continue to make progress in understanding how lower animals can regenerate limbs and organs, the genetic basis for these similarities becomes ever more clear:


"Regeneration of lost limbs is a controlled replication of the processes of embryonic development, while cancer stems from those same processes unleashed and run wild. Nothing is quite as simple as that, of course, but it is a framework for thinking about how these fields of life science research overlap and inform one another. This is well illustrated by a recent advance from one of the research groups studying newt biochemistry with an eye to replicating it in mammals - or at least understanding the crucial differences. We should not be surprised to see that cancer-suppressing genes are at the heart of the puzzle."


The first wave of practical tissue engineering products are in trials, and amongst their number are methodologies for generating large volumes of blood to order.


"Two years ago, DARPA awarded a $1.95 million grant to a Cleveland company called Arteriocyte, which was developing technology that could quickly transform stem cells into red blood cells. The idea was to develop a system that could produce an almost limitless amount of universal donor blood (O-negative) in remote areas. And earlier this month, Arteriocyte submitted samples of their artificially produced blood to the Food and Drug Administration (FDA), seeking approval before making the technology available to both the civilian and military sectors. ... Hematopoietic cells isolated from umbilical cord blood are cultured in an environment that provides them with all the nutrients and molecular signals they need to develop into red blood cells. Currently, it takes about 3 days to generate up to 20 units of transfusion-ready blood from a single unit of umbilical cord blood."


Allow me to direct your attention to a recent update from the SENS Foundation:


"In a typically densely written post over at the SENS Foundation, Michael Rae looks at research into the aging of stem cells, putting it into the context of the SENS view of aging. In short, we know that stem cell populations within the body decline in effectiveness with age, losing their ability to regenerate injuries and maintain tissue in good condition. Researchers are making steady inroads into understanding exactly why this is the case: some of the theories with respectable evidence behind them include damaged signaling mechanisms, damage to the niche cellular environments that support stem cells, an evolutionary adaptation to protect against cancer that might emerge from age-damaged stem cells, or a reduction in the number of active stem cells. These are not all mutually exclusive, of course.

"One of the points Rae makes is that only a few types of cellular and biochemical damage observed in aging are fundamental. Almost all observed forms of decline and damage are secondary effects that will to some degree fade away - repaired by our own regenerative capacity - if the primary forms of damage are removed."

In Rae's own words, "As the regenerative process feeds back upon itself, accelerated with each new therapy applied and each additional form of damage repaired, [we] may hypothesize that the organism as a whole will re-emerge in unexpected ways and with unanticipated inflection points, until we stand restored to the full health, vigor, and capacity of youth."


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!




From the Telegraph: "In as little as five years, researchers hope to be able to coax the heart into regenerating itself, repairing the damage caused by cardiac arrests and old age. ... It works in a similar way to stem cells but instead of the new cells being grown outside the body and then injected back in, the technique simply makes the cells [transform] at the point where they are needed. ... The main problem is that when beating muscles cells - known as cardiomyocytes - die during an attack there is no way to reactivate them and the surrounding connective tissue - known as fibroblasts - cannot take over their role.
Now [researchers] have discovered a way of reprogramming fibroblasts into cardiomyocytes. ... We first have to test if the same factors can convert human fibroblasts to beating heart muscle and then find ways to safely introduce these factors, or small molecules that mimic these factors, into the coronary circulation so they can reprogram the existing fibroblasts in the heart. I envision such factors being loaded into a stent that is placed in the coronary artery and can elute (allow to emerge) the reprogramming factors over 1-2 weeks. ... The team found that they needed a combination of just three substance - Gata4, Mef2c, and Tbx5 - to efficiently convert fibroblasts into cells that could beat like cardiomyocytes."

These researchers argue that embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are most likely the same in any aspect that matters: "the pluripotency of ES cells fueled excitement over their use in regenerative medicine. While ethical hurdles associated with the clinical application of human ES cells appeared to have been overcome with the development of methods to create iPS cells, some recent research has suggested that ES and iPS cells have substantial differences in which sets of genes they express. These findings [argue] to the contrary, rekindling hopes that, under the proper circumstances, iPS cells may indeed hold the clinical promise ascribed to them earlier. ... iPS cells are made by introducing three key genes into adult cells. These reprogramming factors push the cells from a mature state to a more flexible embryonic stem cell-like state. Like ES cells, iPS cells can then, in theory, be coaxed to mature into almost any type of cell in the body. Unlike ES cells, iPS cells taken from a patient are not likely to be rejected by that patient's immune system. This difference overcomes a major hurdle in regenerative medicine. ... At this stage, we can't yet prove that they are absolutely identical, but the available technology doesn't reveal differences. ... Some earlier studies have indicated that iPS and ES cells are dissimilar enough to be classified as different cell types. [The researchers] concluded that the differences noted in other studies were not consistent between different laboratories and thus were not likely to be a result of fundamental differences between the cell types."

A LYSOSENS UPDATE (August 05 2010)
LysoSENS is a project of the SENS Foundation aimed at developing a means to safely remove harmful metabolic byproducts (such as 7KC) that accumulate in lysosomes with age. That buildup degrades the lysosomal ability to clear cells of unwanted junk, which in turn leads to what is known as the garbage catastrophe in aging. At the moment, LysoSENS work focuses on discovering bacterial enzymes that can break down the most important forms of unwanted junk in the lysosome. Here is a progress report from one of the researchers: "The 7KC-degrading bacterium I've been studying, Rhodococcus jostii RHA1, has two large gene clusters that are up-regulated by 7KC, but not cholesterol. In these two gene clusters lie a number of enzymes we believe are involved in 7KC degradation, including an enzyme that could reduce the 7-keto group to a hydroxyl. What makes this interesting to us is that while 7KC is highly cytotoxic, 7alpha-hydroxycholesterol (7alphaOH) is relatively harmless. So I am now methodically going through suspected candidates, searching for reductase activity against 7KC. Currently I am looking at nine different enzymes, and am in various stages of cloning the genes into expression vectors and assaying their products for activity. While I've uncovered some interesting findings, so far I haven’t found the reductase I'm looking for. This could be for several reasons, the first being that I haven't assayed all the enzymes I need to. As I still have the majority remaining, this is a likely scenario. However, one possibility is that the normal substrate for the enzyme is not 7KC, but some downstream metabolite."

Chemical and Engineering News surveys work aimed at replicating the ability of lower animals to regenerate whole limbs and organs: "complicating the attempt to unravel regeneration is the fact that these capabilities change over the lifetime of a single organism. A tadpole, for example, can generally replace a missing tail or limb but loses this ability after its metamorphosis into a frog. Likewise, higher vertebrates such as mammals can regenerate much better during their embryonic and fetal stages than after they have become adults. ... Levin and his collaborator David Kap­lan [are] now testing whether a replicated amniotic environment can promote regeneration in adult mammals. Kaplan has already developed a small, cylindrical 'regenerative sleeve' that can be filled with an aqueous solution and fastened onto the stump of a rat's amputated limb. The sleeve is fitted with a variety of ports and electrical connections so the researchers can sample and alter the container's chemical contents ... the researchers hope to create a regenerative current at the stump's surface by adjusting the ionic composition of the solution inside the sleeve and by adding drugs that open or close ion channels in the membranes of the cells at the wound site. The sleeve will offer some additional benefits. The aqueous environment it provides will prevent the scarring that normally develops in a mammalian wound exposed to air. The researchers might also use it to bathe the wound with scar-reducing compounds, immune-modulating drugs, and more traditional growth factors."

One of the reasons researchers work with flies is that it is comparatively cheap to produce mutant breeding lines - even hundreds of different ones. So studies like this can exist: "To identify genes involved in aging, we assessed longevity in a collection of over 1,300 Drosophila lines ... We found 58 mutations in novel loci that increase life span by up to 33%. Most mutations had different effects on male and female life span, and for some the effects were opposite between the sexes. Effects of these mutations on starvation resistance, chill coma recovery, and climbing ability varied, but all had a deleterious effect on at least one other trait. A sample of ten mutations with increased life span formed genetic interaction networks, but the genetic interactions were different, and sometimes in opposite directions, in males and females. ... Whole-genome transcript profiles of seven of the mutant lines and the wild type revealed 4,488 differentially expressed transcripts, 553 of which were common to four or more of the mutant lines, which include genes previously associated with life span and novel genes implicated by this study. Therefore longevity has a large mutational target size; genes affecting life span have variable allelic effects; alleles affecting life span exhibit antagonistic pleiotropy and form epistatic networks; and sex-specific mutational effects are ubiquitous."

Some variants of mitochondrial DNA are well correlated with longevity; numerous studies have identified SNPs and haplotypes found far more often in long-lived people. This shouldn't be surprising, given the evidence indicating an important role for mitochondria in determining life span. Here is a Chinese study to add to the others: "OBJECTIVE: To investigate the human mitochondrial DNA (mtDNA) variations associated with longevity in Bama elderly population from Guangxi. METHODS: Mitochondrial genome of 20 individuals over 96 years of age was sequenced, and seven target single nucleotide polymorphism(SNPs) were observed by comparing with the standard rCRS sequence, and two were tested by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method in a larger population including 208 individuals of 90-113 years old, and 586 unrelated control individuals from Guangxi. RESULTS: The 4824G frequency of the mtDNA4824A/G locus increased with age both in the long-lived elderly and in controls. And it was significantly higher in controls than that in long-lived population. CONCLUSION: The mtDNA4824 A/G is not only an age-related locus, its mutation is also negatively correlated with longevity."

Via KurzweilAI: "researchers have uncovered a mechanism through which caloric restriction and exercise delay some of the debilitating effects of aging by rejuvenating the connections between nerves and the muscles that they control. ... Their research, conducted through laboratory mice genetically engineered so their nerve cells glow in fluorescent colors, shows that some of the debilitation of aging is caused by the deterioration of connections that nerves make with the muscles they control, structures called neuromuscular junctions. These microscopic links are remarkably similar to the synapses that connect neurons to form information-processing circuits in the brain. ... The work showed that mice on a restricted-calorie diet largely avoid that age-related deterioration of their neuromuscular junctions, while those on a one-month exercise regimen when already elderly partially reverse the damage. ... With calorie restriction, we saw reversal of all of these things. With exercise, we saw a reversal of most, but not all. ... Because of the study's structure - mice were on calorie-restricted diets for their whole lives, while those that exercised did so for just the month late in life - [the researchers] cautioned against drawing conclusions about the effectiveness of exercise versus calorie restriction in preventing or reversing synaptic damage. ... longer periods of exercise might have more profound effects."

"Immortality" is a problematic term, and the press insist on using it when talking about efforts to extend healthy life: "As with cryonics, a proposal to extend life substantially is greeted with bizarre concerns about living too long, or the wrong people living longer. Why not apply such complaints to ordinary medical gains? A big part of the problem, I think, is that talk of 'immortality' invokes an extremely far view. But finite increases in lifespan really have little to do with immortality. Immortality means you never die, ever. But forever is a really really long time! In fact, nothing you can imagine is remotely as long. ... A thousand year lifespan would be fantastic, relative to our lifespan. I want it! But it is nothing like immortality. It would have clear stages, and a very real end to anticipate. Anyone with a halfway decent imagination couldn't remotely run out of new interesting things to do, places to visit, people to see, etc. Yes they'd have time for twenty times as many careers, hobbies, marriages, and vacations as we do now, but it should only take a moment's reflection to realize you there are far more than twenty times as many things to do than we manage in our lives. For example, any decent library holds twenty times more books than you've ever read."

From the Guardian: "What's so wrong with getting old? It is simply that people get sick when they get older. I don't often meet people who want to suffer cardiovascular disease or whatever, and we get those things as a result of the lifelong accumulation of various types of molecular and cellular damage. This is harmless at low levels but eventually it causes the diseases and disabilities of old age - which most people don't think are any fun. Is this the biggest health crisis facing the world? Absolutely. If we look at the industrialised world, basically 90% of all deaths are caused by ageing. They are deaths from causes that affect older people and don't affect young adults. And if we look at the whole world, then the number of deaths that occur each day is roughly 150,000 and about two-thirds of them are because of ageing. ... People have been trying to claim that we can defeat ageing since the dawn of time, and they haven't been terribly successful; there is a tendency to think there is some sort of inevitability about ageing - it somehow transcends our technological abilities in principle, which is complete nonsense. And when people have made their peace with this ghastly thing that is going to happen to them at some time in the distant future, they tend to be rather reluctant to re-engage the question when someone comes along with a new idea."

Over at TechCrunch, the resident jester shows himself to be a deathist - though one shouldn't take anything he writes terribly seriously. It's a funhouse mirror reflection of ill-thought and emotional attitudes to engineered longevity that are in fact held by a great many people. They knee-jerk in favor of what is, or against suspected privilege, without thinking about the mass suffering and death that we could work to prevent: "Oh yes, go to any Silicon Valley party right now and you'll find a scrawny huddle in the corner discussing the science of living forever: a topic that's gone from fringe to hot to cliche in - ironically - less time that it takes a tsetse fly to start getting interested in girls. But then why wouldn’t it when the science of ageing touches on so many valley obsessions? For a start, gerontology is a science. But it's also hacking: human bodies aren't supposed to live much beyond 80, and these are people who would gladly spend a weekend hacking a Furby to make it curse, just because it's not supposed to. ... And so the research goes on, millions more dollars are poured in to deathhacking startups by rich-mortal-and-terrified benefactors, dozens more books are published on the subject and every day countless startup founders jump into their Teslas and speed to their 'doctors' to pick up the latest batch of pills that they hope will keep them around until someone figures this shit out. And why not? Here's why not."


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