Longevity Meme Newsletter, April 20 2009

April 20 2009

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.



- The Hourglass IX Blog Carnival
- Rebooting the Immune System Still Looks Promising
- The Hypoxic Response and Longevity
- Plastinate Everyone
- Discussion
- Latest Healthy Life Extension Headlines


You should add the Hourglass series of blog carnivals to your reading list; it's a good way to find out who out there is talking about aging and longevity science in a serious way.


"The latest Hourglass blog carnival on the biology of aging and longevity science is over at psique, and closes with an interesting historical quote: 'These bodies which now we wear belong to the lower animals; our minds have already outgrown them; already we look upon them with contempt. A time will come when Science will transform them by means which we cannot conjecture, and which, even if explained to us, we could not now understand, just as the savage cannot understand electricity, magnetism, steam. Disease will be extirpated; the causes of decay will be removed; immortality will be invented.' -Winwood Reade, 1872, from his book The Martyrdom of Man"

The difference between Reade's era and ours is that we have a fairly clear vision as to the means by which we will change our bodies for the better. You can read about the scientific details of that vision at the SENS Foundation; each of the tabled links in the following page details one aspect of the research required to repair the damage of aging:



The link below is an update on a trial held a few years ago in which the autoimmune disease of type 1 diabetes was cured by destroying and recreating the patients' immune systems. In essence the flaw in immune system "programming" that caused the disease was eliminated by doing this. That it worked so well is promising, as this is a strategy that could be turned to aspects of aging:


"One component of aging is that we all suffer from increasingly deranged, broken, and misconfigured immune systems. On the one hand your immune system become hyper-sensitive and creates constant low-grade inflammation that causes all sorts of issues, and on the other hand it becomes ineffective at its primary functions - fighting pathogens, killing senescent cells, and eliminating cancer cells. It's on all the time, burning resources and causing damage, but not doing you any good. I look forward to the years ahead in which we can have an old immune system cleared out and reset in an efficient and safe manner, using targeted cell killers and stem cell therapies."


It seems that fooling cells into thinking they're not getting enough oxygen might be as useful to health and longevity as fooling cells into thinking they are not getting as much food as usual:


It remains to be seen whether this can be turned on in addition to calorie restriction to further lengthen healthy life in lesser animals.


It's important to follow ideas to their logical conclusion, even if that logical conclusion is going to get a knee-jerk response from most people. We are all hardwired by evolution to aggressively reject change before reluctantly accepting it - and logical conclusions that suggest change are never going to be well received. As they say, you'll know you have a good idea by the way you'll have to force people to think about it.


"You might recall that [it's] something of an accident of history that the cryonics movement is the cryonics movement versus the plastination movement. Plastination is plausibly just as good a way as low temperature storage of preserving the fine structure of the brain into a future where a patient can be restored to life.

"Not so long ago on the Cryonet list, a fellow asked: 'How can we help those who cannot afford cryonics?' This is a valid question, given that the high level purpose of cryonics is to offer some alternative to oblivion for those who die before the advent of working rejuvenation medicine. While cryonics is very affordable if you plan ahead and take out a low-cost life insurance plan, there will always be those who get caught short through no fault of their own.

"Here, plastination steps forward as a possible alternative that would cost little more than what is already spent on the disposal of remains. Plastinate the brain for the cost of an embalming, and cremate the rest. You're now set for a good number of decades in any very low-cost storage facility."

More than a hundred thousand people died yesterday (and the day before, and the day before that, and ...), most essentially due to aging. These staggering numbers of unique, valuable individuals are lost to oblivion, but the technology exists that could have preserved their minds and given them all a chance at life again in the future. The world we live in is one of great and terrible waste of intelligent life, in comparison to the world in which most people opted to have their brains plastinated ever since it became possible.


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!




A View of Cryonics (April 17 2009)
From Singularity Hub, a piece on cryonics that you might not agree with all of, but is well worth the time to read: "Given the exponential rate of modern scientific innovation, cryonics suggests that new technologies may soon be available that can resurrect an individual considered 'dead' by today's standards. Because our personalities and memories have chemical foundations in the brain, they can hypothetically be preserved in the body, so long as neural tissue does not degenerate (as we'll see, that might be a logical jump). One way of preserving tissue is to store it at extremely low temperatures, effectively grinding your molecular chemistry to a halt. To put it bluntly, the cold keeps your body from rotting. But, as every high school student knows, your body is mostly water, which expands when frozen. This is where a process called vitrification enters the picture. Cryonics patients are preserved in vats of liquid nitrogen cooled to temperatures below -200°F. Because ice crystals can damage cells as they form, the water that fills our cells must be partially replaced before the body is cooled. Chemicals solutions called cryoprotectants are circulated through the patient's body, ultimately reaching a concentration greater than 50%. As the body is cooled, the cryoprotectants allow tissues to reach a glass-like solid state that is relatively free of ice crystals, thus preserving cellular integrity." You might also want to look at Alcor's FAQ for Scientists.

More Digging Into the Mechanisms of Calorie Restriction (April 17 2009)
Some interesting research into the roots of longevity gains through calorie restriction: "Working in yeast cells, the researchers have linked ribosomes, the protein-making factories in living cells, and Gcn4, a specialized protein that aids in the expression of genetic information, to the pathways related to dietary response and aging. ... Previous research has shown that the lifespan-extending properties of dietary restriction are mediated in part by reduced signaling through TOR, an enzyme involved in many vital operations in a cell. When an organism has less TOR signaling in response to dietary restriction, one side effect is that the organism also decreases the rate at which it makes new proteins, a process called translation. ... mutations to the ribosome, the cell's protein factory, sometimes led to increased life span. Ribosomes are made up of two parts -- the large and small subunits ... What we noticed right away was that the long-lived strains always had disruptive mutations in the large ribosomal subunit and never in the small subunit ... depletion of the ribosomes' large subunits was likely to be increasing life span by a mechanism related to dietary restriction - the TOR signaling pathway."

Temperature and Lifespan (April 16 2009)
Body temperature is demonstrated to affect life span in lower animals, and now that researchers are digging into how this works, some of the same longevity mechanisms already discovered in other studies are seen to be involved. Via EurekAlert!: "It's true that [nematode] worms don't regulate their body temperature, but they do regulate their response to high temperature, slowing down processes that would otherwise go much faster. In fact, they even use steroid hormones to do this, just as we do to regulate our temperature ... this might have been a very early evolutionary link between cold- and warm-blooded animals ... the authors suggest that at high temperature, the worm's thermosensory neurons produce a signal that stimulates expression of the daf-9 gene, which produces a steroid hormone that extends lifespan. The researchers propose that this thermosensory system allows C. elegans to reduce the effect that warm temperature would otherwise have on the processes that affect aging, which is something that warm-blooded animals do by controlling the temperature itself. This system may allow the animal to maintain a more normal rate of aging even if the temperature rises ... Previous research also has linked the rate of aging in mammals with temperature. If mice are tricked into thinking that they are in a hot climate, they lower their body temperature and live longer."

An Autologous Stem Cell Trial in the US (April 16 2009)
After a good few years of trials in less oppressively regulated regions of the world, a small autologous stem cell therapy trial has started in the US. "For the first time in the United States, a stroke patient has been intravenously injected with his own bone marrow stem cells ... The Phase I safety trial [will] enroll nine more patients who have suffered a stroke and can be treated with the stem cell procedure within 24 to 72 hours of initial symptoms. ... Animal studies have shown that when you administer stem cells after stroke, the cells enhance the healing. We know that stem cells have some kind of guidance system and migrate to the area of injury. They're not making new brain cells but they may be enhancing the repair processes and reducing inflammatory damage ... This study is the critical first step in translating laboratory work with stem cells into benefit for patients. If effective, this treatment could be helpful to a huge segment of stroke patients to reduce their disability." Remember, if the FDA didn't exist, this type of therapy would already have been benefiting those patients who decided to take advantage of it. It is disingenuous to pretend that great and novel steps are being taken here - this work has already been proven in other parts of the world, and all that is happening now is make-work and obstruction on the part of govenment employees who care little about your health.

Calorie Restriction, Metabolic Rate, and Longevity (April 15 2009)
One of the pieces of evidence that points to our mitochondria as a prime point of interest for engineered longevity is the correlation between maximum life span and resting metabolic rate (RMR) across species. In that light, this research on calorie restriction and metabolic rate is interesting even though it's an insect study: "Caloric restriction (CR) extends lifespan in most animals, but the mechanisms underlying this phenomenon are the subject of much debate. We investigated the association between longevity and resting metabolic rate (RMR) in Indian stick insects (Carausius morosus) [by] quantifying the response of RMR to diet history ... Over a range of body sizes, [RMR] decreased in response to CR, particularly when food was restricted during juvenile stages. With one exception, RMR of insects in different life-history stages matched current feeding level and was not substantially affected by intake history. Total lifespan was affected by intake, with insects that experienced CR early in development living longer than insects that were fed ad libitum. ... CR and decreased RMR were associated with slower progression through pre-reproductive life-history stages."

The Misrepair Accumulation Theory of Aging (April 15 2009)
Here is a twist on the "aging is biochemical damage" viewpoint that theorizes bad repairs to be the important form of damage: "It is now increasingly realized that the underlying mechanisms which govern aging (ageing) are a complex interplay of genetic regulation and damage accumulation. Aging as a result of accumulation of 'faults' on cellular and molecular levels, has been proposed in the damage (fault)-accumulation theory by Kirkwood. However, this theory fails to explain some aging phenotypes such as fibrosis and premature aging, since terms such as 'damage' and 'fault' are not specified. Therefore we introduce here a specification of the underlying mechanism of aging and arrive at a novel theory: aging of the body is a result of the accumulation of Misrepair of tissue. It emphasizes: a) it is Misrepair, not the original damage, that accumulates and leads to aging; and b) aging can occur at different levels, however aging of the body takes place at least on the tissue level, but not necessarily on cellular/molecular level. The novel concept of Misrepair introduced here unifies the understanding of the roles of environmental damage, repair, gene regulation, and multicellular structure in the aging process. The Misrepair-accumulation theory introduced in the present paper gives explanations for the aging phenotypes, premature aging, and the difference of longevity in different species, and is consistent with the point of view of physical theory of complex systems."

Update on Induced Pluripotency Research (April 14 2009)
It is impressive to see how rapidly researchers are moving forward with induced pluripotency. Here's another step forward via EurekAlert!: scientists have "used tiny molecules called microRNAs to help turn adult mouse cells back to their embryonic state. These reprogrammed cells are pluripotent, meaning that, like embryonic stem cells, they have the capacity to become any cell type in the body. The findings suggest that scientists will soon be able to replace retroviruses and even genes currently used in laboratory experiments to induce pluripotency in adult cells. This would make potential stem cell-based therapies safer by eliminating the risks posed to humans by these DNA-based methods, including alteration of the genome and risk of cancer. ... [MicroRNAs] are transient, non-coding molecules that do not incorporate into the genome, but promote self-replication and have the potential to induce pluripotency. They do their thing -- turn a somatic cell into an embryonic stem cell-like one -- and then they're gone ... The goal now is to ensure the safety of induced pluripotent stem cells and to differentiate them into cells that can be used to repair damaged tissue and treat disease."

More Thoughts on Cryonics (April 14 2009)
From Existence is Wonderful: "If you can manage to scrape away enough of the subcultural detritus and personality artifacts that have glommed onto cryonics over the years, what you're left with is: (a) an experiment in tissue preservation, (b) the idea that future technology may someday be able to repair injury and illness not addressable by today's medicine, and (c) a view of death as a process rather than a discrete event. None of these things seem to me particularly irrational or farfetched in and of themselves. Of course in reality you can't actually ignore the cultural connotations and fringe entanglements of something like cryonics. These things must be acknowledged and addressed if one wants to actually have a clear view of the subject, and that's part of what I am trying to do here. E.g., I think the notion of cryonics has been harmed by assertions that it's a means to (even potentially) 'buy immortality'. Immortality, after all, is incoherent - nobody knows how long they or anyone else is going to live, and it might end up being a pretty long time, but it sure as heck isn't going to be forever, any more than having a job gives you a shot at making Infinity Zillion Dollars."

On Preparing For the Future (April 13 2009)
From In Search of Enlightenment: "In the year 2048 the children from my grade 2 class will be the age of many of those in nursing homes today. Globally there will be 2 billion humans alive over the age of 60. And this will bring unprecedented levels of chronic disease (cancer, heart disease, stroke, [Alzheimer's disease], etc.). If there was something we could do to alter this possible future of unprecedented human suffering and disease from becoming a reality, shouldn't we try to avoid it? ... Instead of feeding the next generation of inquisitive thinkers useless platitudes about the importance of switching off lights to save the world we should encourage them to harness the great potential of [our present knowledge of biology to slow or reverse aging itself] ... Given the certainty and severity of the harm of aging you might expect that vast amounts of public funding are being invested in aging research. You might think that the brightest and most talented scientists who long to make the world a better place are being lured into the field. Unfortunately it is very hard to get people to rally behind aging research. This must change. A deceleration of the aging process might make nursing homes a thing of the past. And that would be an enormous achievement that all future generations of humans could enjoy."

SIRT1 and Cancer (April 13 2009)
This research suggests a way in which calorie restriction (which upregulates sirtuins) might be effective in resisting cancer: "The yeast and nematode equivalents of SIRT1 are fountains of youth that stretch lifespan. Whether SIRT1 slows aging in mammals isn't certain, but it's beneficial in other ways. The protein tunes up metabolism, reducing blood levels of glucose and insulin, and might forestall neurodegenerative illnesses such as Alzheimer's disease and ALS. Given its pro-life credentials, you might expect SIRT1 to inhibit cancer. And several studies suggest that it does. But other work indicates that the protein aids tumors. For example, SIRT1 chops off acetyl groups, which can inactivate the tumor suppressor p53. [Researchers] determined SIRT1's effect on the transcription factor c-Myc, whose expression surges in many breast, colon, and liver cancers. The two proteins are tangled in a regulatory loop, the team found. c-Myc latched onto SIRT1's promoter, spurring cells to manufacture more SIRT1. In turn, SIRT1 detached acetyl groups from c-Myc, hastening its breakdown. To test SIRT1's effects on tumor growth, the researchers implanted cancerous cells expressing c-Myc into nude mice that lack immune defenses. Boosting production of SIRT1 blocked tumor formation."



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