Fight Aging!

LONGEVITY MEME NEWSLETTER
March 26 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

- The Edmonton Aging Symposium, March 30th
- Rejuvenation Research, Volume 10, Number 1
- Discussion
- Latest Healthy Life Extension Headlines

THE EDMONTON AGING SYMPOSIUM, MARCH 30TH

Kevin Perrott of the Methuselah Foundation has been hard at work for most of the past year organizing the Edmonton Aging Symposium - and an impressive job he has done. The Symposium starts this Friday, March 30th:

http://www.edmontonagingsymposium.com
http://www.edmontonagingsymposium.com/index.php?pagename=eas_intro

Events include a debate on the ethics of healthy life extension held between Daniel Callahan and Gregory Stock, and presentations by noteworthy speakers such as Ronald Bailey, Aubrey de Grey, Ellen Heber-Katz, Michael West and a range of other scientists working in fields of interest.

The focus here, and the subtitle of the event, is "repairing the damage" of aging. The symposium is an opportunity to showcase and present to the world at large some of the present day scientific research that will form a foundation for the first generation of real rejuvenation medicine. Take a look at the list of speakers and poster sessions, and you'll see what I mean:

http://www.edmontonagingsymposium.com/index.php?pagename=eas_speaker
http://www.edmontonagingsymposium.com/index.php?pagename=eas_poster_session

For those of us scattered around the world, the symposium will be streamed live. To access the stream, register an account on the symposium website, and then select "Internet Access" midway through the following list of options. There is a nominal charge of $5.00 CAD.

REJUVENATION RESEARCH, VOLUME 10, NUMBER 1

The first issue of Rejuvenation Research for 2007 is available online. I picked out a few items of interest for comment in a Fight Aging! post - so jump right on in if you'd like (a) a reminder that scientists speak a language of their own, and (b) to learn a little more about how our biochemistry changes with age:

https://www.fightaging.org/archives/001161.php

"Microglia are a component of the immune system, scavenging debris and defending the central nervous system. ... 'Xenoproteases for bioremediation could be used to enhance intracellular and extracellular proteolytic capacity' means 'let's adopt some useful biochemicals from bacteria that can help microglia clean up cellular debris by degrading harmful metabolic byproducts.' Our metabolism generates damaging chemicals as a side effect of its operation. When these build up with age, they damage the workings of our cells - and thus damage the workings of our bodies. So why not try to help the body out by removing the source of damage?"

Our bodies are a collection of many, many, many moving parts, most of which change and degenerate with age. Developing the tools to solve even a single issue - such as the poor, overwhelmed microglia fighting to keep up in an aging brain choked by a lifetime of metabolic byproducts - is a daunting task, but where else to start on a large job but to set out and repair the first problems you can?

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/

Lysosomal Storage Diseases and Aging (March 25 2007)
http://pmid.us/17329960
Lysosomes are the incinerators of your cells, breaking down junk and old, damaged components, such as mitochondria, so that the raw materials can be reused - a process called autophagy. Some portion of aging is caused by the buildup of materials that the lysosomes cannot degrade, a situation that looks something like lysosomal storage diseases (LSDs) wherein lysosomes are flawed to start with. LSDs "are debilitating genetic conditions that frequently manifest as neurodegenerative disorders. They severely affect eye, motor and cognitive functions and, in most cases, abbreviate the lifespan. Cell death is well documented in parts of the brain and in other cells of LSD patients and animal models ... We suggest that the lysosomal deficiencies in LSDs inhibit autophagic maturation, leading to a condition of autophagic stress. The resulting accumulation of dysfunctional mitochondria [increases] the vulnerability of the cells to pro-apoptotic signals." Which is another way of saying that the worn parts pile up until the cell self-destructs in the process called apoptosis. Some of the possible approaches to dealing with LSDs - such as the bioremediation research funded by Methuselah Foundation donors - are likely to prove useful in reversing this contribution to age-related degeneration.

On Observed Behavior (March 25 2007)
http://infidel753.blogspot.com/2007/03/taking-stand-for-life-revisited.html
Following on from a discussion on priorities and healthy life extension at Fight Aging!, more thoughts from Infidel753: "If I chose to be flippant, I might argue that the number of people who say they would not take advantage of life-extension technology if it were available refutes the proposition that life extension would reduce the death rate to near zero ... Observed behavior is a much better predictor of future behavior than verbal statements are. Many of the dramatic medical innovations of the twentieth century were at first viewed with suspicion as hubristic meddling with nature, but later widely accepted once people got used to them. ... As anti-aging technologies become available, I believe the same process of general acceptance will happen -- probably quite quickly. ... There is a vast difference between contemplating aging and death in the abstract, and confronting them as immediate realities. In fact, almost all humans in situations where they are faced with the possibility of imminent death react by taking any necessary measures to survive. I can't prove it, but I think that almost any person on his deathbed, if offered access to treatment that would restore his health and allow him to return to a normal life, would seize the opportunity, not wave it away."

The Havoc Wrought By CMV (March 24 2007)
http://www.immunityageing.com/content/4/1/2
From the open-access journal Immunity & Aging, a look at cytomegalovirus (CMV) and what it does to your immune system over the years: "Ageing is associated with multiple immune system dysfunctions. An important current direction for immunosenescence research is towards assessing the clinical impact of age-associated modifications of immunity and modulating them. ... Lifelong and chronic antigenic load may represent the major driving force for immunosenescence, which impacts on human lifespan by reducing the number of virgin antigen-non experienced T cells ... Gradually, the T cell population shifts to a lower ratio of naive cells to memory cells ... Thus, the repertoire of cells available to respond to antigenic challenge from previously unencountered pathogens shrinks. ... Many of the clonal expansions filling the individual's immune system seem to result from previous infections by persistent viruses, especially CMV, but also, to a lesser extent, EBV and possibly other herpesviruses. A high number of CD8+ cells are found to be specific for a single epitope of cytomegalovirus: in some individuals up to a quarter of circulating CD8 cells carry receptors for a single CMV epitope." CMV is cluttering your immune system with uselessly specialized cells, leaving you with too few capable defenders in later age - and thus shortening your life.

Patching, Regulation, Trial and Error (March 24 2007)
http://www.usnews.com/usnews/health/articles/070322/22health.parkinsons.htm
Via USNews, an example of the not-so-great methodology of medicine that presently dominates: trial and error over understanding mechanisms; attempting to patch over damage and slow progression of diseases rather than aiming at root causes to repair and reverse them; taking these less effective paths because regulation makes the more effective paths much more expensive. "Researchers are for the first time testing to see if creatine, a nutritional supplement popular with weightlifters, might hold Parkinson's at bay. Creatine works by increasing the body's levels of phosphocreatine, which serves as an energy source for muscle and brain. In Parkinson's, nerve cells in the brain are damaged and eventually die. 'We're not entirely sure what the reason is for the cell death. One reason might be that the cells run down; they lose energy. Creatine feeds into the little power plants, the mitochondria, that provide energy for the cell. ... Creatine is one of several over-the-counter supplements being investigated as a Parkinson's treatment.' There you have it - unambitious, of only minor benefit even if successful, yet forging ahead. An example in miniature of everything that is wrong with medical research and development today.

Growing Replacement Enamel (March 23 2007)
http://www.eurekalert.org/pub_releases/2007-03/iaa-srd030707.php
Dentists are eagerly embracing regenerative medicine, as well they might. Here, EurekAlert! reports on progress towards one component of new teeth: "Dental enamel is the hardest tissue produced by the body. It cannot regenerate itself, because it is formed by a layer of cells that is lost by the time the tooth appears in the mouth. The enamel spends the remainder of its lifetime vulnerable to wear, damage, and decay. For this reason, it is exciting to consider the prospect of artificially growing enamel, or even whole teeth, using culturing and transplantation techniques. In the emergent field of tooth-tissue engineering, several groups have developed their own approaches. Although there has been some success in producing enamel-like and tooth-like tissues, problems remain to be solved before the technology comes close to being tested in humans. One of the issues has been how to produce, in culture, sufficient numbers of enamel-forming cells. ... Now that dental epithelial cells can be propagated in culture, the next step will be to achieve the same success with their partners in tooth formation, the dental mesenchymal cells. Further development of this technique will be aimed toward production of tissue to replace damaged or missing enamel, and ultimately, regeneration of whole teeth."

1% Of Novamente Donated To the Methuselah Foundation (March 23 2007)
http://blog.methuselahfoundation.org/2007/03/novamente_joins_the_methuselah.html
Illustrating the strong connection between the general artificial intelligence community and healthy life extension community, the owners of Novamente have donated 1% of their company in support of meaningful longevity research: "Currently in stealth mode, San Francisco-based Novamente is working on revolutionary Artificial Intelligence products. The Methuselah Foundation is a non-profit 501(c)(3) organization dedicated to accelerating the development of foreseeable, science-based therapies to combat aging. ... We are grateful to Novamente for its generous donation, the first we hope of many that will follow as part of the Methuselah Foundation's newly launched '1% for Life' program, for far-sighted corporations that want to support the rapidly accelerating efforts to find solutions to the debilities caused by aging. ... Since both Novamente and the Methuselah Foundation are operating at the leading edge of scientific progress, we at Novamente appreciate the enormous benefits that progress in Artificial Intelligence and Life Extension will confer on humanity. We consider our donation a wise investment in a brighter future for us all."

"Cellular Aging Is a Reversible Process" (March 22 2007)
http://dx.doi.org/10.1016/j.mad.2006.11.020
An interesting abstract published earlier this year: "Ageing is often defined in the context of telomerase activity and telomere length regulation. Most somatic cells have limited replication ability and undergo senescence eventually. Stem cells are unique as they possess more abundant telomerase activity and are able to maintain telomere lengths for a longer period. Embryonic stem cells are particularly resistant to ageing and can be propagated indefinitely. Remarkably, adult somatic cells can be reprogrammed to an ESC-like state by various means including cell fusion, exposure to ESC cell-free extracts, enforced expression of specific molecules, and somatic cell nuclear transfer. Thus, the rejuvenation of an 'aged' state can be effected by the activation of specific key molecules in the cell. Here, we argue that cellular ageing is a reversible process, and this is determined by the balance of biological molecules which directly or indirectly control telomere length and telomerase activity, either through altering gene expression and/or modulating the epigenetic state of the chromatin."

Scaffolds To Regenerate Ligaments (March 22 2007)
http://www.technologyreview.com/printer_friendly_article.aspx?id=18421
(From the Technology Review). Scientists continue to explore the use of scaffolds to convince the body to heal and regrow where it normally will not: "Surgical reconstruction is typically required to repair the [anterior cruciate ligament (ACL)], but current methods continue to take significant recovery time, during which a patient may sustain a loss of strength and function. Now, [researchers]have bioengineered a new ACL replacement using a 3-D polymeric fiber braiding process. It's the first synthetic scaffold design to demonstrate exceptional tissue regeneration and healing, and it could lead to a promising ligament-replacement technology. ... Our goal was to regenerate the ACL using classic design principles from engineering and material that has mechanical properties that mimic the natural ACL ... There just hasn't been very much successful work done on tissue-engineering ligaments. This [is] a very significant discovery. I haven't seen anybody do what they are doing with ligaments before." This work is still in the animal study stage; a few years yet before human trials start by the look of it.

The State of Stem Cells and Heart Disease (March 21 2007)
http://www.technologyreview.com/printer_friendly_article.aspx?id=18414
A reminder from the Technology Review that for all the speed of modern stem cell science, turning knowledge into new therapies is a slower process; the devil is in the detail and the regulation. "It's a tantalizing thought: injecting stem cells isolated from a person's own blood into an ailing heart in hopes of repairing years of accumulated decay. But so far, human trials testing cell therapies for heart attacks have yielded mixed results, creating controversy over various aspects of the treatment: the types of cells that are used, the way they are delivered, and when in the course of the disease they are given. With the next round of trials, scientists hope to nail down the precise set of conditions needed to effectively heal a sickly heart. ... In terms of the clinical testing of stem-cell therapies, heart disease is arguably the furthest along of the common diseases. But cell-based therapies are proving trickier to test than traditional drugs and medical devices are. They seem to require the perfect combination of ingredients and execution. Scientists must determine the best cells to transplant, the best way to prepare cells, and when and how they should be delivered."

More On Nanofactories (March 21 2007)
http://www.sciencedaily.com/releases/2007/03/070320125351.htm
An interesting hint of medicine to come from ScienceDaily; nanofactories, tiny artificial structures that act like cells: "these ingested nanofactories, using magnetism, could detect a bacterial infection, produce a medication using the body's own materials, and deliver a dose directly to the bacteria. The drug would do its work only at the infection site ... we can produce a tiny nanofactory and attach it to a target cell magnetically. The nanofactory then makes small molecules from surrounding materials and delivers the molecules - potentially drug molecules - to the targeted cell. ... the nanofactory could produce signaling molecules that communicate with the target cell or block the target cell from communicating with other, similar cells (a process called 'quorum sensing') and thus prevent infection. The researchers attached the nanofactories to E. coli cells, targeting them with the help of a mixture of iron particles and chitosan ... The nanofactories then produced a signaling molecule that could render the E. coli harmless. Nanofactories could be designed to produce the needed drug molecules over an extended period of time."

A Look At Cancer Vaccine Research (March 20 2007)
http://www.sciencedaily.com/releases/2007/03/070319180031.htm
Cancer vaccines have been in the popular science press over the past couple of years. Here is more from ScienceDaily: "At the root of most cancers is a single cell going awry and dividing uncontrollably, producing a tumor. As cells become cancerous, they produce proteins that are unfamiliar to the human immune system, which should prompt a protective response from the body. Yet somehow, these stealth proteins evade the body's defenses and allow the cells to grow into a tumor. In results from animal studies, pre-vaccination with these foreign proteins creates an immune response that prevents the tumor from forming. Unfortunately, each tumor's protein signature can be slightly different. In other words, even if two individuals have the same type of cancer, their tumors may be slightly different, and therefore the concept of a widespread preventative vaccine that would be effective in large numbers of people has been a daunting task. However, if common themes could be identified, it could provide a means for solving this problem." We should all be most interested in progress towards the defeat of cancer - the longer you live, the more likely it is that you'll experience it.

More Viruses Versus Cancer (March 20 2007)
http://medicalnewstoday.com/medicalnews.php?newsid=65408
Scientists are making strides in adapting various viruses to kill cancer - there is a certain satisfaction inherent in turning the tools of disease for use in healing. Medical News Today tells of another groups hard at work to this end: "an attenuated -- or non-virulent -- form of poliovirus is effective in obliterating neuroblastoma tumors in mice, even when the mice had been previously vaccinated against the virus. By its nature, poliovirus destroys the cells it infects in an attempt to replicate copies of itself. ... The [researchers] took advantage of this viral property by injecting a stable, attenuated strain of poliovirus directly into neuroblastoma tumors transplanted into 12 mice engineered to contract polio. The virus was able to destroy tumors in all 12 mice; however tumors reoccurred in two mice by the end of the 180-day study period. .... None of the mice experienced any ill effects from the virus itself. ... any viral particles that make it to the bloodstream would be destroyed by antibodies created through poliovirus vaccination. The researchers believe that their findings, if developed to work in humans, could represent a safe, practical means of treating [many] other cancers in adults."

A Glance at Basic Stem Cell Research (March 19 2007)
http://www.newswise.com/articles/view/528206/
A release at Newswise is indicative of the sort of progress presently underway in the study of stem cell biochemistry. Piece by piece, scientists are uncovering the knowledge needed to fully control our cells, and thereby regenerate damage on demand: "A newly discovered small molecule called IQ-1 plays a key role in preventing embryonic stem cells from differentiating into one or more specific cell types, allowing them to instead continue growing and dividing indefinitely ... This discovery takes scientists another step closer to being able to grow embryonic stem cells without the 'feeder layer' of mouse fibroblast cells that is essential for maintaining the pluripotency of embryonic stem cells ... Such a layer is needed because it is currently the only proven method to provide the stem cells with the necessary chemical signals that prompt them to stay undifferentiated and to continue dividing over and over. ... Stem cells that grow on feeders are contaminated with mouse glycoproteins markers. If you use them into humans, you'd potentially have a horrible immune response. ... If we can create a totally chemically defined system for growing human embryonic stem cells without any risk of contamination, it would make life much easier for scientists than it is at the moment. And that's our goal."

Thoughts on Aging Research (March 19 2007)
http://www.medicalnewstoday.com/medicalnews.php?newsid=65473
An interesting piece from Medical News Today: "The early development of humans and animals, the time between conception and maturity, has an enormous influence on their lifespan. ... Zwaan [had] just been stressing how important it is for the medical world to become convinced that factors at the very start of life have an enormous influence on life expectancy. So that we can make an early start on taking appropriate, and preferably preventive, action. Don't wait until middle age! ... Early influences late. But how does it work? We're all well aware by now that pregnant women shouldn't smoke. But there are many more things we are not aware of. These are the things we want to find out more about. And more importantly: we want to understand the biology behind them. ... From time to time somebody will claim to have found the gene for longevity. The rest of the field is then silenced. And it means so little. The fact that a mutated gene may lead to longer life, does not mean that the gene contributes to variation in natural populations, including that of man." It makes for interesting reading in the context of the reliability theory of aging and longevity, which suggests we are born with an initial load of damage.

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