Longevity Meme Newsletter, November 02 2009

November 02 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.



- Why Advocacy for Longevity Science?
- Priorities in Regenerative Medicine Research
- On the Manipulation of Heat Shock Proteins
- An Update on Our Folding@home Team
- Discussion
- Latest Healthy Life Extension Headlines


A call to action from one of the Immortality Institute volunteers:


"Will we reach the point of Longevity Escape Velocity, and thus live on in good health for centuries, sustained by ever more effective advances in longevity medicine? Many of us ask ourselves this question, unsure of how the research community is doing: who is working on what, and how fast or slow are they moving? We think that maybe 'they' can get the job done in 25 years, maybe 45, maybe 75, 100, 1,000 ... we don't know.

"Here is the good news for we who wonder: WE ARE 'THEY'. Progress occurs at the rate at which we collectively make it happen. We are the people who build the future, not some faceless and unknown 'they': if we work harder, the future arrives more rapidly. If we slack off, the future drifts away into the distance. In these early years, in which persuasion is as valuable as lab work, every volunteer hour dedicated to helping advance medical technology is priceless. Who are the volunteers? Us. It is you and I that must contribute the time and make the difference. It is our contributions that snowball over time into the determination of whether we live or die: does longevity-enhancing medicine arrive within our lifetimes, or will we just miss the boat?"


I thought I'd share a very interesting open access review paper that identifies present areas of focus in the field of regenerative medicine by counting papers published. To me, at least, the present breadth of work on regenerating brain cells is surprising - and welcome:


"I find it reassuring to see a heavy focus on neuroscience in regenerative medicine research. A few years spent watching progress in medical research has not changed my opinion on the need to develop repair technologies for the brain. It is the most vital end result. Our brains are the big deal - the big, complex, show-stopping deal - in regenerative medicine. It doesn't matter how well everything else goes if we can't figure out how to restore damage, age-related or otherwise, in a brain in situ.

"All things considered, generating new, healthy human organs looks well on track to being a solved problem and available in the clinic within the next two decades. Researchers can presently grow bone in specific shapes in situ, and take complex organs from animals or human donors and replace all the tissue with the patient's own cells. This suggests that, even discounting the many other lines of tissue engineering research proceeding in parallel, all of the major organs will be replaceable for people who can tolerate the surgery required - except for the brain.

"Restoring the brain will require a greater level of understanding as to how cells, regeneration, and growth are programmed and controlled. The end goal might be something like a steady flow of new, undamaged neurons to take the place of those that are lost. In conjunction with therapies to deal with the other aspects of age-related damage, such as the buildup of aggregates seen in Alzheimer's disease, that would go a long way towards setting up a brain for the long term. Or at least long enough for medical science to advance far beyond the bounds of present speculation."


I think there's a fair case to be made for heat shock proteins to be the next big thing in the field of metabolic manipulation aimed at inducing enhanced health and longevity:


"Heat shock proteins are molecular chaperones, and their activities in the body are boosted by exercise and calorie restriction, two line items known to extend healthy life in laboratory animals and produce impressive health benefits in humans. Put simply: molecular chaperones detect proteins that are misfolded, and have the ability to refold those proteins into the appropriate, non-toxic shape. Additionally, if the protein is so badly misfolded that it cannot be repaired, the molecular chaperones can also recruit other proteins that have the ability to 'tag' the toxic protein for destruction by the cell.

"Damaged proteins and damaged cellular components are themselves a source of further damage, as they cause the cell's machinery to run awry - and aging itself is nothing more than the accumulation of damage and its side-effects. The goal of a number of groups working on heat shock proteins is, ultimately, to slow down the progression of aging by boosting the beneficial activities of these and other chaperones."


Protein folding is important in biochemistry, as misfolded proteins can cause all sorts of havoc. A better understanding of protein folding may lead to therapies for a range of age-related and other conditions. Competitive distributed computing programs such as Folding@home (F@h) are making inroads in this field by modeling the folding (or misfolding) of specific proteins thought to cause issues.

I continue to be very impressed by the way in which the Longevity Meme F@h team moves from strength to strength, but credit where it is due:


"Back in the day I started up the Longevity Meme F@h team because neurodegenerative diseases of aging, such as Alzheimer's disease (AD), were high on the F@h organizers' priority list. The team might have remained a small affair of a few dozen folk, just like thousands of other teams - certainly I had no world-spanning ambitions for it at that point. But a few persistent and highly effective organizers from the Immortality Institute took it upon themselves to grow the team relentlessly; in the years of their involvement, they have made a real success of this contest. That the Longevity Meme F@h team today consists of hundreds of members and is ranked 70th in the world is entirely to the Immortality Institute volunteers' credit. If renaming of teams was permitted, I would have long ago changed the name to reflect the source of its success."


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!




Our immune systems can destroy cancer - but the immune system grows less effective with age, and sometimes it fails in this task. That "sometimes" is enough to kill a quarter of humanity, the fraction of us who die from cancer. Researchers are closing in on the mechanisms that separate success from failure, however, and in the years ahead will be able to tune our immune systems to destroy cancer nearly 100% of the time: "A specific type of T helper cell awakens the immune system to the stealthy threat of cancer and triggers an attack of killer T cells custom-made to destroy the tumors ... The role of Th17, one of only four known types of T helper cell, opens a possible avenue for overcoming cancer's ability to suppress or hide from the body's immune system ... While there is much work to be done, these preclinical findings imply the possibility of taking a patient's Th17 cells, expanding them in the lab, and then re-infusing them as treatment ... Development of a vaccine to stimulate Th17 cells would be another possible application."

The Baltimore Longitudinal Study on Aging has been running since 1958, but this Canadian study is just getting started - a much larger project planned to run for decades: "Canadians are living longer, and older persons are making up a larger share of the population (14% in 2006, projected to rise to 20% by 2021). The Canadian Longitudinal Study on Aging (CLSA) is a national longitudinal study of adult development and aging that will recruit 50,000 Canadians aged 45 to 85 years of age and follow them for at least 20 years. All participants will provide a common set of information concerning many aspects of health and aging, and 30,000 will undergo an additional in-depth examination coupled with the donation of biological specimens (blood and urine). The CLSA will become a rich data source for the study of the complex interrelationship among the biological, physical, psychosocial, and societal factors that affect healthy aging." I suspect that the most important role for these studies in the future will be to more rapidly evaluate the effectiveness of specific longevity therapies as they arrive in the clinic.

TEDMED DAY 2 COVERAGE (October 29 2009)
From MedGadget: "Also before lunch was the science of aging pair up with Aubrey de Grey, CSO of the SENS Foundation, and David Sinclair, professor at Harvard Medical School. If you've not heard of these gentlemen before, both view aging as a disease but both are approaching aging in very different ways. Aubrey spoke first and has a more futuristic view of aging. His mantra is that aging is metabolism caused cellular damage that leads to organism pathology, and the human body, just like cars, can be made to run longer with adequate maintenance and repair. He views age related problems as belonging to seven types and in order to tackle aging, all seven cellular and molecular problems need to be cured. Aubrey also coined the idea of a Longevity Escape Velocity (LEV), which is the point of life span where progress in aging science is occurring faster than the degradation of the body itself. He believes that if someone is able to live to 150 years old, then by that point the progress in the ability to keep them alive will be faster than their rate of death, thus they will live into their 1000s. Still focused on the same target, but shooting from a different angle was David Sinclair, who focuses his research on a set of proteins called sirtuins."

Will it be possible to use patient-derived cell transplants to heal the brain in much the same way as can be done with other organs? From EurekAlert!: researchers have "found that using an animal's own brain cells (autologous transplant) to replace degenerated neurons in select brain areas of donor primates with simulated but asymptomatic Parkinson's disease and previously in a motor cortex lesion model, provides a degree of brain protection and may be useful in repairing brain lesions and restoring function. ... We aimed at determining whether autografted cells derived from cortical gray matter, cultured for one month and re-implanted in the caudate nucleus of dopamine depleted primates, effectively survived and migrated. The autologous, re-implanted cells survived at an impressively high rate of 50 percent for four months post-implantation ... Researchers found that the cultured cells migrated, re-implanted into the right caudate nucleus, and migrated through the corpus callosum to the contralateral striatum. Most of the cells were found in the most dopamine depleted region of the caudate nucleus. This study replicated in primates the success the research team had previously reported using laboratory mice."

TEDMED DAY 1 COVERAGE (October 28 2009)
From MedGadget: "we heard from a series of speakers involved with regenerative medicine. Daniel Kraft (flashback: MarrowMiner) spoke of the role of stem cells in medicine and how he discovered a better way to harvest them from the pelvis. Damien Bates, the chief medical officer of Organogenesis, the company behind biologic wound healing film Apligraf, passed around a sample of their wound healing tissue for people to feel as well as talked about how the skin heals and how it can be aided by regenerative biology. Anthony Atala, from the Wake Forest Institute for Regenerative Medicine, talked about the various methods his research center is using to grow specific tissues and organs. He described much of the tissue creation process as sort of building the layers of a cake, with each tissue type placed one on top of the other. For linearly organized organs, such as arteries, this isn't so much of a problem, because you can just grow layers upon layers of tissues. However, for the more complicated, highly solid organs with lots of blood vessels, this methodology breaks down, and the scientists have to either use some sort of pre-made matrix or need to harvest tissues from other sources and de-cellularize them, leaving behind only the collagen scaffold that can be populated by cells."

From the IEET Blog, a look at plausible outcomes in advancing computational power and biotechnology - such as being able to emulate a human brain in software. I have no doubt that this will happen within the next few decades, but is it desirable? A human mind running on software could last as a pattern for as long as civilization persists, but unless deliberately engineered for continuity it would not survive as an individual in the way we presently understand that term. For example: we are quite used to moving data from hard drive to hard drive, restoring from backups when data becomes corrupt, and constantly shifting the running of software from machine to machine. Cost-effective human emulations would likely undergo exactly these sorts of events under the hood. If you are concerned with personal continuity, as I am, this would be an existential nightmare - you would exist as a flickering series of different people, each one killed by the normal operation of computing systems, and then the next picks up where the prior left off. Yet it will be quite possible to engineer an artificial brain in software and hardware that has continuity in the same way as we do presently: a collection of nanomachines, each machine playing the role of a single neuron, for example. That strategy is probably not cost-effective in comparison to running everything in software, however - and most people won't care about the existential issues so long as everything looks good from the outside.

The trend in human longevity is upward, but how much of that is due to unintended slowing of the aging process via general advances in medicine and better treatment of the diseases of aging? A paper: "The distinction between senescent and non-senescent mortality proves to be very valuable for describing and analysing age patterns of death rates. Unfortunately, standard methods for estimating these mortality components are lacking. The first part of this paper discusses alternative methods for estimating background and senescent mortality among adults and proposes a simple approach based on death rates by causes of death. The second part examines trends in senescent life expectancy (i.e., the life expectancy implied by senescent mortality) and compares them with trends in conventional longevity indicators between 1960 and 2000 in a group of 17 developed countries with low mortality. Senescent life expectancy for females rises at an average rate of 1.54 years per decade between 1960 and 2000 in these countries. The shape of the distribution of senescent deaths by age remains relatively invariant while the entire distribution shifts over time to higher ages as longevity rises."

This seems potentially important: "Despite a 30-year lifespan that gives ample time for cells to grow cancerous, a small rodent species called a naked mole rat has never been found with tumors of any kind - and now [biologists] think they know why. ... the mole rat's cells express a gene called p16 that makes the cells 'claustrophobic,' stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells' growth barely changed ... Like many animals, including humans, the mole rats have a gene called p27 that prevents cellular overcrowding, but the mole rats use another, earlier defense in gene p16. Cancer cells tend to find ways around p27, but mole rats have a double barrier that a cell must overcome before it can grow uncontrollably. ... It's very early to speculate about the implications, but if the effect of p16 can be simulated in humans we might have a way to halt cancer before it starts. ... We haven't come across this anticancer mechanism before because it doesn't exist in the two species most often used for cancer research: mice and humans. Mice are short-lived and humans are large-bodied. But this mechanism appears to exist only in small, long-lived animals."

Opinions from a bioethicist on how researchers should present the case for longevity science in order to maximize fundraising and public support: "The medical sciences are currently dominated by the 'disease-model' approach to health extension, an approach that prioritizes the study of pathological mechanisms with the goal of discovering treatment modalities for specific diseases. This approach has marginalized research on the aging process itself, research that could lead to an intervention that retards aging, thus conferring health dividends that would far exceed what could be expected by eliminating any specific disease of aging. This paper offers a diagnosis of how this sub-optimal approach to health extension arose and some general prescriptions concerning how progress could be made in terms of adopting a more rational approach to health extension. Drawing on empirical findings from psychology and economics, 'prospect theory' is applied to the challenges of 'framing' the inborn aging process given the cognitive capacities of real (rather than rational) decision-makers under conditions of risk and uncertainty. Prospect theory reveals that preferences are in fact dependent on whether particular outcomes of a choice are regarded as 'a loss' or 'a gain', relative to a reference point (or 'aspiration level for survival'). And this has significant consequences for the way biogerontologists ought to characterise the central aspirations of the field (i.e. to prevent disease versus extend lifespan)." Personally, I'm more in favor of entirely the opposite approach - don't adapt your argument to the suboptimal cultural environment, but rather work to change that cultural environment.

Progress continues in the development of biochemically active scaffolding to sculpt and guide tissue regeneration: here, ScienceDaily looks at a scaffold "made from soluble fibers, which may help humans replace lost or missing bone. With more research, [it] could also serve as the basic technology for regenerating other types of human tissues, including muscle, arteries, and skin. ... The bioactive agents that spur bone and tissue to regenerate are available to us. The problem is that no technology has been able to effectively deliver them to the tissue surrounding that missing bone. [This] artificial and flexible scaffolding connects tissues together as it releases growth-stimulating drugs to the place where new bone or tissue is needed - like the scaffolding that surrounds an existing building when additions to that building are made. ... The [scaffold material] could be used to restore missing bone in a limb lost in an accident, or repair receded jawbones necessary to secure dental implants ... The scaffold can be shaped so the bone will grow into the proper form. After a period of time, the fibers can be programmed to dissolve, leaving no trace."



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