Fight Aging!

LONGEVITY MEME NEWSLETTER
May 28 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.

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CONTENTS

- Watch For the Mitochondrial Repair Technology
- Calorie Restriction Research Fundraiser
- Discussion
- Latest Healthy Life Extension Headlines

WATCH FOR THE MITOCHONDRIAL REPAIR TECHNOLOGY

One of the news items in this week's newsletter relates to Telomolecular's interest in repairing mitochondria, the energy producers of the cell that evolved from symbiotic bacteria and still carry their own DNA outside the cellular nucleus. Recall that accumulated mitochondrial damage and a Rube Goldberg mechanism in the cells is at the heart of the modern free radical theory of aging:

https://www.fightaging.org/archives/000994.php

This acquisition on the part of Telomolecular might be a matter of sensibly broadening their portfolio from a focus on telomeres, but recent research suggesting mitochondrial damage is at the root of telomere shortening - itself linked to aging and the target of a number of development initiatives - leads one to speculate on just who is aiming at what result here:

https://www.fightaging.org/archives/001204.php

Present details aside, keep an eye on the development of mitochondrial repair technologies. Given the strong role of mitochondria, free radicals and oxidative damage in aging, the potential is here for the next step on the ladder in healthy life extension medicine. The regulatory environment - "aging is not a disease, and we only approve treatments for disease" - will lead to funding and trials for mitochondrial diseases rather than aging, but the technology base will still be developed, ready for the time when people finally overturn the present unfortunate regulation of real longevity medicine.

One group has already demonstrated the capacity to completely replace damaged mitochondrial DNA in a living being with fresh new material, for example, and is presently somewhere in the process of forming a company and obtaining funding for further development:

https://www.fightaging.org/archives/000539.php

Other researchers are proceeding along the SENS road - moving critical mitochondrial genes into the cellular nucleus to make the accumulation of damage irrelevant:

https://www.fightaging.org/archives/000622.php
http://www.methuselahfoundation.com/index.php?pagename=mitosens

You'll have to go back and read that first link on the free radical theory of aging for an explanation as to why moving those genes should have just as good an effect as repairing all the DNA in your mitochondria. But my point is that movement is underway; I expect to see a brace of new companies focused on developing mitochondrial repair technology emerge in the next few years. Exciting times!

CALORIE RESTRICTION RESEARCH FUNDRAISER

The Calorie Restriction Society is continuing its initiatives in support of human calorie restriction research with an August benefit event:

https://www.fightaging.org/archives/001226.php

"People from all over the world will converge from Friday, August 10 through Sunday, August 12 on the village of Tarrytown, New York, near Sleepy Hollow, where Washington Irving spun his yarn of 'The Headless Horseman.' But this is a meeting of facts, not fiction. It is a workshop on calorie restriction, the only scientifically proven way to slow aging. ... The workshop is a benefit for the continuation of a milestone research project on the effects of calorie restriction on humans. Initiated in cooperation with the Calorie Restriction Society by Drs. Luigi Fontana and John Holloszy, of Washington University Medical School in Saint Louis, the first two phases of the research have discovered new knowledge that allows people everywhere to better understand how to prevent disease associated with aging.

"A highlight of the workshop will be presentations by Dr. Fontana and by Dr. Stephen Spindler, whose genetic analysis of calorie-restricted animals has garnered worldwide acclaim. Dr. Spindler will lead the exploration of the genetic and cell signaling patterns of human calorie restrictors in Phase Three of the research whose funding is spearheaded by the Calorie Restriction Society."

The evidence has been racking up ever more rapidly in past years. If you haven't yet given calorie restriction at least a little thought, you should:

https://www.fightaging.org/archives/2002/11/calorie-restriction-explained/

DISCUSSION

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!

Reason

Founder, Longevity Meme
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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/

More Mice Full of Amyloid Beta (May 27 2007)
http://www.sciencedaily.com/releases/2007/05/070503165315.htm
Interesting animal model research from earlier this month I managed to miss, via ScienceDaily: "Tau is made normally by brain cells and regulates the stability of their internal skeleton. In [Alzheimer's disease (AD)], tau is altered in a way that makes it aggregate into clumps, called tangles. A lot of effort has been devoted to finding ways to specifically eliminate these abnormal forms of tau, but this has been difficult. ... Many investigational therapies for AD aim to reduce levels of amyloid-beta proteins (AB) because Amyloid-beta builds up to abnormally high levels in the brains of people with AD and is widely suspected to cause the disease. ... We wanted to pursue a complementary strategy and try to make the brain more resistant to A-Beta without having to change the levels of A-Beta itself. Amazingly, even partial reduction of tau prevented memory problems and premature deaths in our Alzheimer mice, even though their brains were full of amyloid beta." This looks to be related to Buck Institute research from last year, which also demonstrated healthy mice full of amyloid beta.

A Look at Nanomedicine (May 27 2007)
http://www.nanowerk.com/spotlight/spotid=1975.php
Following up on some of their previous articles, Nanowerk looks again at nanomedicine: "Nanotechnology promises us a radically different medicine than the cut, poke and carpet bomb (think chemotherapy) medicine of today. The two major differences of nanomedicine will be a) the tools it uses - the main workhorse will be [multifunctional nanoparticles] - and b) it will enable a perfectly targeted and individual treatment: organs and bones, really any body tissue, can be diagnosed and treated on a cell by cell basis with precise dosing and monitoring through the use of biomolecular sensors. ... Looking into the future, Freitas envisions 'biocompatible surgical nanorobots that can find and eliminate isolated cancerous cells, remove microvascular obstructions and recondition vascular endothelial cells, perform noninvasive tissue and organ transplants, conduct molecular repairs on traumatized extracellular and intracellular structures, and even exchange new whole chromosomes for old ones inside individual living human cells.'"

More Signs of the Obvious (May 26 2007)
http://winnipegsun.com/Business/2007/05/26/4209582-sun.html
Via the Winnipeg Sun, more signs of the incidental healthy life extension brought by advances across the board in medicine: "A new study on aging and retirement -- the largest study of its kind ever undertaken -- says that people are living longer and better health than ever before ... The HBC study -- conducted with the Oxford Institute of Ageing, which surveyed 21,000 people in 21 countries including Canada -- found that people the world over now able to live the lives the age of 70 that previous generations would have enjoyed at 50. People in their 60s and 70s generally feel in good health, and there are only small differences between people of this age and those in the 40s and 50s in terms of control and quality of life. ... older workers and retirees are better able to significantly contribute to society because they are more fit and active than ever before. They also feel they are in control of their lives and are generally looking forward to the next 20 to 30 years of their life. ... People in their 60s and 70s are a tremendous asset to society, not generally a burden." Showing the world that healthy longevity is increasing is only one part of the education process, however: we also have to help people understand that progress depends on action; that each and every one of us can step up to make the process move faster.

Alliance For Aging Research Seeks Director of Development (May 26 2007)
http://asi.careerhq.org/jobdetail.cfm?job=2575072
The Alliance for Aging Research is seeking a director of development: "This 20-year-old healthcare non-profit is recognized as the leading authority and advocate for healthy aging research. It is backed by a strong and diverse Board of Directors, representing companies, foundations, and patient advocates which supports scientific and medical discoveries to maximize healthy aging, independence and quality of life for older Americans. The organization is seeking a Director of Development who will be passionate about the potential of medical research to improving the lives of older Americans. ... The Director of Development works closely with the Executive and Deputy Director and is a senior member of the leadership team. Working closely with the Board and staff, this individual is responsible for formulating, implementing and directing the fundraising strategies for the organization. S/he will lead their team in carrying out a comprehensive development plan incorporating all levels of fund raising." The Alliance is one of the backers of the Longevity Dividend initiative; if you support that direction for longevity research and development, there are few better opportunities to step in and help directly.

A Review of Primate Calorie Restriction (May 25 2007)
http://pmid.us/17223278
A reminder, in the form of a review paper, that the evidence for calorie restriction (CR) as the best presently available method of increasing health and longevity is compelling: CR "is the only intervention repeatedly demonstrated to retard the onset and incidence of age-related diseases, maintain function, and extend both lifespan and health span in mammals, including brain and behavioral function. In 70 years of study, such beneficial effects have been demonstrated in rodents and lower animals. Recent results emerging from ongoing studies of CR in humans and nonhuman primates suggest that many of the same anti-disease and anti-aging benefits observed in rodent studies may be applicable to long-lived species. Results of studies in rhesus monkeys indicate that CR animals (30% less than controls) are healthier than fully-fed counterparts based on reduced incidence of various diseases, exhibit significantly better indices of predisposition to disease and may be aging at a slower rate based on analysis of selected indices of aging. The current review discusses approaches taken in studies of rhesus monkeys to analyze age-related changes in brain and behavioral function and the impact of CR on these changes."

Arthritis, Pain and a Gene Therapy (May 25 2007)
http://www.eurekalert.org/pub_releases/2007-05/uorm-egt052507.php
From EurekAlert!: "Early-stage research [in mice] has found that a new gene therapy can nearly eliminate arthritis pain, and significantly reduce long-term damage to the affected joints ... If all goes well with a follow-up study currently underway, researchers will apply [to] begin human trials next year. ... researchers used gene therapy to increase by about one thousand times the number of opioid receptors expressed on the surfaces of nerve cells that carry pain messages back and forth between an osteoarthritic jaw joint and the spinal cord. ... nerve cells involved in pain transmission [became] drastically more responsive to the naturally occurring painkiller ... [this] work has contributed to the emerging theory that pain is not a symptom of osteoarthritis, but is instead part of the disease. According to this new paradigm, pain is composed of nerve messages that over time cause permanent chemical changes in the pathways they travel along, making them more sensitive to pain and encouraging inflammation. This two-way 'crosstalk' may mean that arthritis in one joint can spread, through the central nervous system (CNS), to other joints. Worse yet, joint arthritis may export inflammation to the brain, where it plays a role in neurological conditions (e.g. Alzheimer's disease, dementia and multiple sclerosis)."

Better Biochemistry in Centenarians (May 24 2007)
http://pmid.us/17518695
As scientists continue to explore centenarian biochemistry, they are uncovering the details of its better performance: "Oxidative DNA damage has been implicated in the aging process and in some of its features such as telomere shortening and replicative senescence. Poly(ADP-ribosyl)ation is involved in many molecular and cellular processes, including DNA damage detection and repair, chromatin modification, transcription, and cell death pathways. We decided to examine the behavior of poly(ADP-ribosyl)ation in centenarians, i.e., those subjects who represent the best example of longevity having reached a very advanced age avoiding the main age-associated diseases. ... Our data show that cells from centenarians have characteristics typical of cells from young people both in their capability of priming the mechanism of repair after [oxidative damage] and in poly(ADP-ribosyl)ation capacity, while in cells from old subjects these phenomena are delayed or decreased. ... Our data support the hypothesis that this epigenetic modification is an important regulator of the aging process in humans and it appears to be rather preserved in healthy centenarians, the best example of successful aging."

Mechanisms of Alzheimer's Immunotherapy (May 24 2007)
http://www.medicalnewstoday.com/medicalnews.php?newsid=71862
A snapshot of some of the present work on developing an Alzheimer's vaccine can be found at Medical News Today: "One of the things those earlier immunotherapy studies taught us was that antibodies can reduce amyloid plaques, which are a hallmark of the disease. The next logical question was -- how does it do that? ... Instead of working outside the cell, we discovered that these antibodies to beta amyloid bind with a specific part of amyloid precursor protein (APP) -- a precursor molecule to beta amyloid -- as it lies on the outside of the affected cell. This complex then gets internalized within the cell, where it works to decrease levels of amyloid peptides, the building block of plaques that are found outside and between cells ... How might antibodies working inside neurons decrease exterior plaque levels? The researchers still aren't sure, but they have already ruled out some of the most obvious answers ... What is clear from the study is that immune-based therapy does work to rid brain cells of amyloid -- giving new impetus to the search for a safe, effective Alzheimer's vaccine."

More On the Path to Brain Regeneration (May 23 2007)
http://www.the-scientist.com/news/home/53238/
As reported by The Scientist, researchers continue to work on better understanding the mechanisms by which new neurons are created in adult brains: "Not only are the new neurons connected up early, but they are showing a form of synaptic plasticity that we know is associated with learning very early on ... It's a different environment but basically [adult cells] do exactly the same thing normally a young cell would do in fetal development ... That is very interesting to show that after let's say two months, the newborn neurons could become identical to preexisting neurons. That was not known. ... he plans to investigate the molecular mechanisms that determine how young cells incorporate into old circuitry. The findings may ultimately help reveal how stem cell therapy can repair the brain. Ideally, a few new neurons will rejuvenate the system, he said. ... the idea is emerging that adaptation of old circuitry or increasing plasticity of the old circuitry can help with recovery."

Telomolecular Aims at Mitochondrial Repair (May 23 2007)
http://www.checkbiotech.org/orphan_News_treatmentandhealth.aspx?infoId=401
This is most interesting: "Telomolecular Corporation [recently] acquired a new technology from Stanford Leland Jr. University. The technology, called Mitofusin 1, allows for the repair of damaged mitochondrial DNA. Damage to mitochondrial DNA leads to forms of aging and a variety of diseases. By combining this tool with other portfolio products Telomolecular hopes to reverse certain symptoms and signs of human aging. ... The correction of damaged mitochondrial DNA may have applications in human aging. An unfortunate side effect of aerobic respiration in mitochondria is that unstable molecules called reactive oxygen species (ROS) begin to accumulate in the mitochondrial DNA compartment and cause damage to mitochondrial DNA. The intentional mutation of mitochondrial DNA in lab animals causes premature aging ... Additionally, mitochondrial DNA mutations are found to accumulate with age in humans." Telomolecular has been focused on working with telomeres in the recent past, but is now joining a select few groups aiming to block the mechanisms of the mitochondrial free radical theory of aging.

The False Hopes of Recent Centuries (May 22 2007)
http://pmid.us/17509279
Evidence of the quest for extended healthy longevity can be found for any period in human history; it is a tragedy that only now are we comparatively close to success. Each of us stands near the peak of a mountain of death, suffering, ignorance and failed hopes; any glance at the history of medicine should remind us of that fact: "During the 19th and early 20th centuries there was great interest in antiaging remedies. This search for the eternal fountain of youth stemmed from the concept of aging as a pathological condition that destroyed the body and mind. In addition, great emphasis was placed on the economic challenge that the elderly presented to society. ... The history of antiaging medicine includes a variety of remedies. E. Metchnikoff advocated a diet rich in lactic acid which he thought would eradicate the body of intestinal putrefaction and decay. Others believed the fountain of youth lay within the endocrine system. ... The early 20th century was marked by a number of surgical attempts at the restoration of youth. L. L. Stanley reported on more than 643 inmates at the San Quentin prison on whom he had performed testicular transplantation. This idea of gland grafting gained international interest and led others such as S. Voronoff to experiment with the transplantation of various animal glands into humans."

Exercise, Mitochondria and Gene Expression (May 22 2007)
http://www.eurekalert.org/pub_releases/2007-05/bifa-era051507.php
One result of the ongoing biotechnology revolution will be precise answers as to how and why exercise is good for healthy longevity. From EurekAlert!: a study "involved before and after analysis of gene expression profiles in tissue samples taken from 25 healthy older men and women who underwent six months of twice weekly resistance training, compared to a similar analysis of tissue samples taken from younger healthy men and women. ... The gene expression profiles involved age-specific mitochondrial function; mitochondria act as the "powerhouse" of cells. Multiple studies have suggested that mitochondrial dysfunction is involved in the loss of muscle mass and functional impairment commonly seen in older people. The study was the first to examine the gene expression profile, or the molecular 'fingerprint', of aging in healthy disease-free humans. ... in the older adults, there was a decline in mitochondrial function with age. However, exercise resulted in a remarkable reversal of the genetic fingerprint back to levels similar to those seen in the younger adults. The study also measured muscle strength. Before exercise training, the older adults were 59% weaker than the younger adults, but after the training the strength of the older adults improved by about 50%, such that they were only 38% weaker than the young adults."

Towards Molecular Automata For Medicine (May 21 2007)
http://www.eurekalert.org/pub_releases/2007-05/hu-iaf051707.php
In the same vein as artificial cells as medical machinery for the 2010s and 2020s, EurekAlert! reports on researchers developing molecular machinery for similar purposes: scientists "have made a crucial step toward building biological computers, tiny implantable devices that can monitor the activities and characteristics of human cells. The information provided by these 'molecular doctors,' constructed entirely of DNA, RNA, and proteins, could eventually revolutionize medicine by directing therapies only to diseased cells or tissues. ... Each human cell already has all of the tools required to build these biocomputers on its own. All that must be provided is a genetic blueprint of the machine and our own biology will do the rest. Your cells will literally build these biocomputers for you ... The biocomputers' 'input' is RNA, proteins, and chemicals found in the cytoplasm; 'output' molecules indicating the presence of the telltale signals are easily discernable with basic laboratory equipment. ... These biocomputers can translate complex cellular signatures, such as activities of multiple genes, into a readily observed output. They can even be programmed to automatically translate that output into a concrete action, meaning they could either be used to label a cell for a clinician to treat or they could trigger therapeutic action themselves." It's a whole new century out there.

Life, Death and Progress (May 21 2007)
http://betterhumans.com/blogs/anne/archive/2007/05/20/trends-in-attitudes-toward-life-death-and-progress.aspx
Via Betterhumans, Anne C.'s essay on attitudes towards fundamental truths and our ability to enact change: "Given the current (nascent) state of true longevity research, it remains to be seen whether tangible advances in life extension medicine will result in the depopularization of the 'death is natural' argument. Either people will decide that their sense of identity requires the 'aging into death' story lest they risk profound existential confusion, or they will concede that, now that we can actually 'do something' about aging, they're not actually all that keen on undergoing senescence. From the standpoint of longevity advocacy, the second outcome is certainly the preferred one -- for the same reason that most of us would consider it better for a friend contemplating suicide to determine that life is worth living after all and not go through with the act of killing himself. When a person has spent enough time in the healthy life extension community, it is quite likely that even poetic-sounding arguments like 'death is natural, it's part of the circle of life' will start to sound indistinguishable from statements like, 'I have a death wish for myself and everyone else in the world.'"

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