LONGEVITY MEME NEWSLETTER
July 02 2007
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.
- Repairing Mitochondria To Help Thwart Aging
- Latest Healthy Life Extension Headlines
REPAIRING MITOCHONDRIA TO HELP THWART AGING
Mitochondria are the power plants of your cells, evolved from symbiotic bacteria and bearing their own DNA. They transform food into the molecule ATP, used by cellular processes for energy, but mitochondria and their DNA become damaged and mitochondrial function declines with advancing age. As more is discovered and the tools of modern biotechnology improve, the repair of damaged mitochondria as a strategy to help halt or reverse aging looks ever more plausible with each passing year.
In recent months, some researchers have suggested that ongoing decline in mitochondrial function is the cause of two other biochemical processes linked with aging and specific age-related conditions. Firstly, that shortened telomeres rest on mitochondrial damage:
Secondly, that declining ability to repair DNA damage also might have the same root cause:
Both DNA damage and telomere shortening are widely considered to contribute to age-related degeneration - as for so much of aging science, definitive mechanisms and absolute answers are still up for debate, however. Neither of the "mitochondria did it" proposals above has yet had time to be widely debated and further investigated, but this is not to mention the direct role of mitochondrial DNA damage in causing age-related degeneration in the well-supported mitochondrial free radical theory of aging:
A successful strategy to defeat aging - defeat, not just slow - must look at the biochemical changes that occur with aging, treat those changes as damage, and repair them. We shouldn't follow the cues of past decades and merely aim to patch over the symptoms of aging, or merely aim to slow aging, as that is an expensive way of failing. The more that researchers understand our biochemistry, the better they can identify which age-related changes are truly fundamental - to strike at the root, with less effort and more rapid results. But as for the bridge builders of past millennia, we don't necessarily need complete understanding to start now and produce good work:
It will be fortunate if mitochondrial damage turns out to be a more important root cause of aging than previously thought, as scientists have already created technology demonstrations for a variety of ways to repair that damage ... or make it irrelevant. In the latter category are efforts to move fragile mitochondrial DNA - genes - into the well-protected cellular nucleus. These efforts received a boost with recently published work:
"The job of a gene is, in essence, to act as the instruction set for the production of proteins, the components of cellular machinery. A core problem in moving the factory from the mitochondria to the nucleus is that these proteins would then have to struggle their way back to the mitochondria where they are needed; this has been a challenge for a variety of reasons.
"These researchers have demonstrated a way to overcome that challenge for at least a subset of mitochondrial genes - via what might be viewed as a rather clever hack to the programming of the cell - and thus can repair dysfunctional mitochondria that results from damage to those genes and a local absence of vital proteins."
Pay attention to the work taking place in laboratories today and tomorrow - medical science is the future of our healthy longevity.
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!
Founder, Longevity Meme
LATEST HEALTHY LIFE EXTENSION HEADLINES
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/
Apoptosis and the Aging Immune System (June 29 2007)
Beyond the exhaustion of immunological space due to cytomegalovirus, there are other contributing factors leading to the degeneration of the immune system: "Immunosenescence is characterized by a peculiar remodeling of the immune system, mainly induced by lifelong antigenic burden and oxidative stress. Apoptosis or programmed cell death plays a central role in the ageing process. ... The apoptosis remodeling, in addition to inflamm-ageing, i.e. the upregulation of anti-stress responses and inflammatory cytokines, represents one of the major determinants of ageing rate and longevity, as well as of the most common age-related diseases. ... A correct modulation of apoptosis may be useful for prolonging the lifespan or at least reducing age-related degenerative, inflammatory and neoplastic diseases whose incidence increases with age. This review [highlights] emerging anti-ageing therapeutical strategies offered by apoptosis re-modulation. The challenge for the future is to identify factors and signals that regulate apoptotic processes and determine if selective apoptosis manipulation [could] preserve immune function in the elderly." Through increased understanding comes the possibility of action for increased healthy longevity.
Telomere Shortening and Aging (June 29 2007)
Whatever the mechanisms linking shortening telomeres to aging, the decline appears to accelerate at age 50: "Telomeres play a role in cellular aging and they may also contribute to the genetic basis of human aging and longevity. A gradual loss of the telomeric repeat sequences has been reported in adult tissue specimens. ... There was a tendency that the age-adjusted telomere length was longer in females than that observed in males, while males lose the telomeric sequence faster than females. These data indicated that the percentage of longer telomeres fragments decreased, while the shortest fragments increased quickly with age. In addition, the longest telomere fragments decreased and the short fragments increased with a relatively stable frequency with age. There was also a significant difference in the longest telomere fragment percentage between males and female in their 40s and 50s ... the changing rate of the longest and the shortest range group [seemed] quite different before and after [age 50.] This contrast implies a drastic change around the age of 50 of unknown factors that affect telomere attrition."
Manipulating Regeneration in Dentistry (June 28 2007)
As Medical News Today notes, dentists push the boundaries of regenerative medicine just as hard as other researchers. One approach is to manipulate cells already in the body to greater efforts by delivering or altering control signals: "The carrier [GAM, a polymer matrix] serves as a scaffold that holds exogenous genes in situ until endogenous wound-healing cells arrive. Up to 50% of available healing repair cells will get gene transfer. Then the cells in the matrix carrier act as local in vivo bioreactors, producing new gene-coding proteins that augment tissue repair and regeneration. GAM implantation at sites of bone injury is associated with retention and expression of the gene of interest for at least 6 weeks. ... At day 7, we observed that the GAM porous architecture provided scaffolding to promote cell ingrowth. The local granulation tissue fibroblasts, along with capillaries, migrated into the GAM. The osteogenic progenitor cells within the tissue uptook the local plasmid DNA and transiently expressed the gene. This leads to a significant augment in periodontal bony tissue regeneration."
The Role of DNA Damage in Aging (June 28 2007)
A paper by Aubrey de Grey outlines his view of nuclear DNA damage and aging: "Since Szilard's seminal 1959 article, the role of accumulating nuclear DNA (nDNA) damage - whether as mutations, i.e. changes to sequence, or as epimutations, i.e. adventitious but persistent alterations to methylation and other decorations of nDNA and histones - has been widely touted as likely to contribute substantially to the aging process throughout the animal kingdom. Such damage certainly accumulates with age and is central to one of the most prevalent age-related causes of death in mammals, namely cancer. However, its role in contributing to the rates of other aspects of aging is less clear. Here I argue that, in animals prone to cancer, evolutionary pressure to postpone cancer will drive the fidelity of nDNA maintenance and repair to a level greatly exceeding that needed to prevent nDNA damage from reaching levels during a normal lifetime that are pathogenic other than via cancer or, possibly, apoptosis resistance." In other words, beyond sufficient work to prevent cancer, we don't need to repair nuclear DNA over a human lifetime. Maybe. This debate is ongoing; there are many others who argue that DNA damage is an important root cause of aging.
Signs of the Times (June 27 2007)
(Via CBS News). There are more positive views of radical life extension in the mainstream press these days: biomedical gerontologist Aubrey de Grey "feels that people can live to be 1,000 years old without suffering any of the bad things usually associated with old age. ... He went on to say, 'I think the first person to live to 1000 might be 60 already.' Hello! Get in line behind me. ... He is optimistic that the mouse trials, followed by the human trials, should only take another 25 years or so. In other words, if we can all just hang on for another 25 years, each of us might be able to live to be 1,000. Just try not to get hit by a car for the next quarter of a century. Needless to say, there are quite a few scientists who don't take de Grey very seriously. ... But let's give de Grey and those who believe in his theory the benefit of the doubt for a moment. ... Would we benefit from the wisdom of older people who had seen so much? Would human accomplishments be greater than today because everyone would be able to develop to his or her own potential? ... The interesting thing about this kind of speculation is that it brings up the idea of whether there is ever an age when people should be considered 'old enough' to die. A 20-year-old may feel that a person who is 94 has lived a long and full life, and that nobody should feel bad if he dies at that age. However, when that young person ages and becomes 93, he no longer feels that way about 94. Most of us probably think 1,000 is too old for a person to live. But will we still think that when we're 999?"
Progress In Engineered Skin (June 27 2007)
The Telegraph reports on progress in producing replacement skin: "Scientists said that the successful tests, in which laboratory-made living human skin was fully and consistently integrated into the human body for the first time, marked a clinical breakthrough in regenerative medicine. ... Intercytex said the new skin - called ICX-SKN - appeared to incorporate itself much better with real tissue than any other skin substitutes tried in the past, which biodegrade in situ after a few weeks. The researchers hope it might provide an alternative to skin grafts, which are often used for victims of serious burns and large wounds. ICX-SKN is created from a matrix produced by the same skin cells that are responsible for synthesising new tissue in the body. Results show that the new skin had produced a closed and healed wound site after just 28 days. ... To have an off-the-shelf skin replacement product that can be used in large numbers of patients will revolutionise the treatment of burned and skin damaged patients."
Metabolic Rate and Free Radicals (Again) (June 26 2007)
Not to hammer on the point, but I find this worth looking at twice, given the importance of mitochondria and free radicals to aging: "increases in longevity during dietary restriction can occur together with lack of decreases or even increases in [oxygen (O2)] consumption. This is frequently interpreted as contradictory with the mitochondrial free radical theory of aging. But this is based on the erroneous assumption that increasing O2 consumption must increase the rate of mitochondrial oxygen radical generation. Here it is shown that the opposite occurs [during] aerobic exercise bouts, chronic exercise training, and hyperthyroidism, and notably, during dietary restriction. Mitochondrial oxygen radical generation is also lower in long-lived birds than in short-lived mammals of similar body size and metabolic rate. Total rates of reactive oxygen species generation can also vary between tissues in a way not linked to their differences in oxygen consumption. All this indicates that mitochondrial reactive oxygen species (ROS) production is not a simple byproduct of mitochondrial respiration. Instead, it is regulated independently of O2 consumption in many different physiologic situations, tissues, and animal species. Thus, the apparently paradoxical increases in O2 consumption observed in some models of dietary restriction do not discredit the mitochondrial free radical theory of aging, and they can further strengthen it."
More Common Sense From Eliezer Yudkowsky (June 26 2007)
There's nothing more outlandish than people who think that working towards the defeat of age-related suffering and death is outlandish: "A transhumanist says unconditionally: 'Life is good, death is bad; health is good, death is bad.' Whether you're 5, 50, or 500, life is good, why die? Nothing more is required. Then why is there a widespread misunderstanding that transhumanism involves a special fetish for technology, or an unusually strong fear of death, or some other abnormal personal disposition? ... Correspondence bias can also be seen as essentialist reasoning, like explaining rain by water spirits, or explaining fire by phlogiston. If you kick a vending machine, why, it must be because you have a vending-machine-kicking disposition. So the transhumanist says, 'Let us use this technology to cure aging.' And the reporter thinks, How strange! He must have been born with an unusual technology-loving disposition. Or, How strange! He must have an unusual horror of aging!"
Regenerating From Deafness (June 25 2007)
(From EurekAlert!). Many stem cell therapies under development are in effect attempts to manipulating biochemical signaling systems into causing more regeneration than would otherwise happen. The stem cells used substitute for our present inability to directly and safely manipulate those signaling systems: "Hearing loss has many causes, including genetics, aging, and infection, and may be complete or partial. Such loss may involve damage to inner ear cells called cochlear fibrocytes, which are fundamental to inner ear function. Some natural regeneration of these cells can occur after acute damage, leading to partial recovery of temporary hearing loss. But could such restoration be enhanced by using bone marrow stem cells, which can differentiate into various tissue-specific cell types ... Stem cells injected into the inner ear survived in half of the injured rats, where they migrated away from the site of injection toward the injured region within the inner ear. These stem cells divided in the new environment and expressed several proteins necessary for hearing, suggesting tissue-specific differentiation. ... Importantly, transplanted rats exhibited faster recovery from hearing loss, particularly in the high frequency range, which is difficult to restore by natural regeneration."
Presuming to Exist (June 25 2007)
A good piece from Anne C.: "Why must death, specifically age-related death (of all things) be singled out as some sort of cosmically significant defining factor of what it means to be a person? There are so many things in life that one might garner meaning from, after all -- art, beauty, love, friendship, creativity, excitement, learning, awe, wonder, and even the constant and unrelenting struggle to make meanings in a universe that frequently seems to be patently absurd. To deny the possibility of continued existence to full, valuable, loved individuals on the basis that this might somehow undermine the significance of life and personhood is beyond discriminatory. It is beyond presumptuous. Why not let people determine for themselves what it means to exist rather than presuming to decide for them on the basis of outmoded notions of everyone needing a guaranteed (probably age-related) end in order to truly appreciate and participate in life? This is perhaps one of the most confounding things for me in terms of arguments against the idea of healthy life extension -- the idea that somehow, the 'wisdom of nature' suggests that we are all part of some grand circle that demands our demise within but a few decades of our birth."