Longevity Meme Newsletter, February 18 2008

February 18 2008

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.



- Inserting Repair of Aging into Tissue Engineering
- The Partial Immortalization Approach
- Discussion
- Latest Healthy Life Extension Headlines


The basic plan behind much of today's tissue engineering research is to (a) generate stem cells from the patient, (b) use those stem cells to build new tissue to replace damaged or lost tissue. Both of these points are a challenge when you're down in the trenches - everything related to the complexities of biology is far from simple. Thus a new technique that makes either (a) or (b) much less costly will boost the rate of progress in research and application. Here's one potential example:


"Reprogramming adult stem cells into embryonic stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine. A patient's skin cells, for example, could be reprogrammed into embryonic stem cells. Those embryonic stem cells could then be prodded into becoming various cells types - beta islet cells to treat diabetes, hematopoetic cells to create a new blood supply for a leukemia patient, motor neuron cells to treat Parkinson's disease."

Looking ahead to the future, perhaps the most interesting part of this path for tissue engineering is the point early in the therapy at which you have a small collection of stem cells isolated from the patient. Right at that point, there is the opportunity to apply any form of newly developed repair technology to erase damage caused by aging or disease, thereby ensuring that the tissue grown from the stem cells is undamaged:


"For example, lengthening telomeres, or correcting simple genetic errors. These are things that can be done today in a limited fashion - we don't fully understand the consequences, and our knowledge is small in the grand scheme of things. That won't always be the case, however, and this point of opportunity in the growth of new tissue tailored for the individual will remain as we find new and better ways to take advantage of it.

"The damage of aging in our cells is 'just' a wrong arrangement of molecules, when it comes down to it. It seems plausible that selecting the least damaged cells, or repairing specific forms of damage - such as replacing age-damaged mitochondria with freshly repaired versions - is a near-future approach to minimizing the damage of aging in induced pluripotent stem cells.

"One caveat: it looks likely that the behavior of stem cells, or any new tissue, in the body has a great deal to do with the holistic functioning of signaling networks and the cellular environment. You can't just take the cells in isolation when thinking through potential technologies and applications - you have to consider the aged environment of the surrounding tissue."



Similar to the techniques described above, but much more comprehensive in scope, is a research and development plan labeled "partial immortalization" by researcher Attila Chordash. He describes a path to radical life extension via expansion of the capabilities of regenerative medicine and tissue engineering. I discussed that a little way back in the archives:


"In order to make yourself physically younger, you must remove the molecular damage of aging within cells - either by replacing cells (such as entire stem cell populations) with less damaged cells, or by repairing that damage. Those are much the same thing if you want to replace cells with more of your own cells grown to order; you have to find a way to repair the damage of aging inside cells one way or another. You can't just regenerate - you must also rejuvenate by repairing this damage to cellular mechanisms."


The highlights and headlines from the past week follow below.

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To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/

The Power of Targeting, Modularity (February 15 2008)
Via EurekAlert!, one example of work to combine targeting mechanisms with anti-cancer mechanisms to safely attack cancer cells. Here, researchers "slowed the growth of two particularly stubborn solid tumor cancers - neuroblastoma and peripheral nerve sheath tumors - without harming healthy tissues by inserting instructions to inhibit tissue growth into an engineered virus ... this [therapy] enhanced anti-tumor activity by stimulating multiple biological processes, including directly killing the cancer cells and reducing the formation of blood vessels that fed the tumors ... oncolytic herpes simplex virus (oHSV) and similar viruses can infect and kill human cancer cells without harming normal, healthy cells or causing disease. [Researchers armed] oHSV with a gene that carries instructions for a cancer-fighting protein, human tissue inhibitor of metalloproteinase 3 (TIMP3). TIMP3 blocks enzymes that aid the development and progression of cancer, called matrix of metalloproteinases (MMP)." While this is not as effective as other examples, the present breadth of exploratory work in targeted cancer therapies is impressive. Most importantly, even partial successes yield improved component parts for other targeted therapies - the modularity of this work greatly speeds overall progress.

The Guardian on Cryonics (February 15 2008)
The Guardian looks at modern day cryonics and its goals: "First, cryopreservation techniques need to improve so patients' bodies - and especially their brains, the repositories of memory and personality - suffer minimal damage. Second, the medical techniques for [revival] must be developed. ... If we succeed in our mission, cryonics will become a process carried out in hospitals by medical staff for much shorter times. ... That in itself is a change from the early days. [The] demographics are changing. Formerly, most cryonicists were young, male and geeky. Now, Alcor gets whole families. The important unknown is: Can a cryosuspended brain, warmed and revived, retain the memories and personality of its owner? ... I think within 30 years we'll see a successful revival, but the people revived then would be cryopreserved 30 years from now. ... Last in, first out: the earliest patients to be cryopreserved suffered the worst damage. James Bedford, who in 1967 became the first person ever to be cryonically suspended and who is now at Alcor, was barely perfused at all. ... For the people being cryopreserved now, under the best conditions, my guess is 50 to 100 years. ... Given the current rate of medical progress and research into nanotechnology [if] we haven't done it in 100 years, it's not going to work." How far we've come in the past decade, to see respectful, balanced articles on the serious work of the cryonics community as the new media norm.

Bone Regeneration Trials (February 14 2008)
News-Medical.Net passes along results of a trial for another first generation stem cell therapy. It's a clear improvement over presently widespread procedures for repairing bone injuries. The trial "involved 10 patients with leg fractures which refused to heal ... All the patients have apparently new bone formation and seven patients have achieved union of their long bone defects within an average of 4.9 months; three others continue to show progressive new bone formation. Before the stem cell implantation none of the 10 had shown any evidence of new bone formation for 5 to 41 months; the seven with the successful long bone union have been able to fully weight bear and resume daily activities. ... The study found there was a direct relationship between increasing the dose of stem cells implanted and shortening the time to heal the bony defect, which the researchers say indicates that the stem cells work in a similar way to a pharmaceutical drug."

Thoughts on Epigenetics, Damage and Aging (February 14 2008)
You might recall the reliability theory of aging and longevity, with its implication that we are born with a surprisingly high level of existing damage, reducing our life span. There is also the relationship between solar radiation during pregnancy and resulting life expectancy. Here's a paper speculating on the mechanics that might link early environmental circumstances with the odds on life span: "Recently a cluster of new hypotheses of aging has been suggested, which explicitly predict the importance of early-life events in health and life span modulations. It has been widely assumed that these long-lasting consequences of early-life exposures may depend on the same mechanisms as those underlying 'cellular memory,' that is, epigenetic inheritance systems. There is a growing body of evidence that environmentally induced perturbations in the epigenetic processes (which involve alterations of gene expression without a change in DNA sequence) can determine different aspects of aging, as well as [cause and course] of age-related diseases."

An Interesting View of Telomeres (February 13 2008)
This unorthodox overview of telomere biology is well worth your time: "Telomeres are highly dynamic structures that adjust the cellular response to stress and growth stimulation based on previous cell divisions. This critical function is accomplished by progressive telomere shortening and DNA damage responses activated by chromosome ends without sufficient telomere repeats. Repair of critically short telomeres by telomerase or recombination is limited in most somatic cells, and apoptosis or cellular senescence is triggered when too many uncapped telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germ line that typically express high levels of telomerase. In somatic cells, the telomere length typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age."

A Return to the Ethical Imperative (February 13 2008)
A bioethical examination of the documentary "Do You Want To Live Forever?" can be found at BioethicsBytes: "ultimately it's a matter of choice. Do we want to continue our youthful lives of the people who are already alive, or do we want to have turn-over of people dying ... and being replaced by people who are born? ... [Aubrey de Grey] acknowledges that people may have different opinions about which of these options is the most desirable, but argues that if we are able to extend healthy lifespan and thereby avoid people having to die horribly our ethical obligations lie with those who are already alive. Thus, de Grey's arguments suggest that research and development into life-extension technology is, not only desirable, but an ethical imperative. He positions this choice as both the individual and societal level." That modern societies operate as though there is a "social level," at which the few can force their decisions upon the many, is the real problem. Healthy life extension technology is, fundamentally, the greatest possible expression of individual choice - the choice to keep on living in good health, one day at a time, and the choice to work towards creating a future in which that will always be possible.

What We Know About Stem Cells and Aging (February 12 2008)
A good overview of the present consensus on stem cells and aging can be found at Science News Online: "over the past few years, researchers have found stem cells in many, perhaps most, of the body's organs and tissues. Even the brain, which scientists once thought never replaced its nerve cells during adulthood, is now known to have stem cells that make new nerve cells throughout life ... Imagine that, as a person ages, these fountains of cellular youth might start to run dry. As the supply of fresh cells dwindles, tissues would gradually decline and show signs of age. 'That was the initial mode' of how stem cells could be involved in aging ... Yet evidence is mounting that the connection between adult stem cells and aging is more complex. Some kinds of stem cell actually grow more abundant with age. And just as stem cells affect aging, the aging body affects stem cells. ... Whether the bodily declines that come with aging are due to the depletion of stem cells depends on which organ is in question - and on which scientist you ask. ... There's still a tremendous amount of debate about even the [blood stem cell] system, which is one of the best-studied systems."

Aubrey de Grey on the Colbert Report (February 12 2008)
Biomedical gerontologist Aubrey de Grey, the quintessentially English driving force behind the Methuselah Foundation and SENS research, appeared on the Colbert Report last night - all very last minute for advance warning and confirmation as so many of these television shows are. A healthy discussion is underway over at the Immortality Institute: "Just saw him on the re-air, awesome to see him on the Colbert Report. I remember people suggesting on here that Aubrey should go on the show, but others figured that would never happen ... never say never. Great way to expose the Methuselah Foundation. ... [That] was great! Aubrey handled the interview really well. ... I'm fairly convinced that scientists will collectively come to the same conclusion that majority of non-genetic disorders are all related to the aging process, a process that can be modified to obviate it's deleterious effects. Some of us have simply realized this sooner than the rest of the world and have a head-start. It'll sink in. We just need more Aubrey's shouting this from rooftops."

Common Sense and Those "Modifiable Factors" (February 11 2008)
No new information here, but frequent reminders never hurt: researchers "studied a group of 2,357 men who were participants in the Physician's Health Study. At the beginning of the study, in 1981 to 1984, the men (average age 72) provided information about demographic and health variables, including height, weight, blood pressure and cholesterol levels and how often they exercised. ... A total of 970 men (41 percent) lived to age 90 or older. Several modifiable biological and behavioral factors were associated with survival to this exceptional age. ... Smoking, diabetes, obesity and hypertension significantly reduced the likelihood of a 90-year life span, while regular vigorous exercise substantially improved it. ... Adverse factors associated with reduced longevity - smoking, obesity and sedentary lifestyle - also were significantly associated with poorer functional status in elderly years." Take care of the health basics today to improve your chances of living into the era of working rejuvenation technology.

A Popular Science View of Longevity Research (February 11 2008)
From Popular Mechanics: "We've long regarded aging as something almost mystical or supernatural, and it's easy to see why. ... But research demonstrates that aging isn't a supernatural procĀ­ess; it's a physical one that gradually occurs as systems wear out beyond the body's ability to repair them. Cells fill up with metabolic debris called lipofuscin that they can't digest, accompanied by decreasing functionality. They also undergo glycation, gumming up and caramelizing with sugars that have bonded to proteins. Mitochondrial DNA can suffer mutations, and the body slowly loses stem cells, which weakens healing and repair. Aging is breakdown, but broken things can be fixed. After all, cars and airplanes tend to wear out as they get older, but with sufficient maintenance they can last far beyond their design life. ... Americans now live longer, healthier lives by several decades than the majority did a century ago. Most of us think it's a good thing. Would extending this phenomenon by several more decades be good, too? Seems like it to me."



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