Fight Aging!

LONGEVITY MEME NEWSLETTER
October 16 2006

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

- AGE-Breakers Beyond Alagebrium
- Thesis: Dying to Life Forever
- Discussion
- Latest Healthy Life Extension Headlines

AGE-BREAKERS BEYOND ALAGEBRIUM

One of the ways in which normal metabolic processes degrade important components in your body is through the generation of advanced glycation endproducts (AGEs). Your body needs certain proteins in order to work properly; the creation of AGEs involves taking two or more of these proteins and sticking them together with chemical gunk, preventing them from doing their jobs. Day in and day out, this is taking place in your body, as a normal and expected side effect of metabolism.

Problems caused - or not helped - by AGE buildup include kidney disease, and the many variations of blood pressure and heart conditions caused by a lack of elasticity in the tissues of heart and blood vessels. Given enough time, your AGEs will conspire to kill you - and the problems they cause along the way will contribute to other age-related degeneration.

Fortunately, there are classes of chemical compound - drugs, in other words - that could break up the AGEs that are leading you part of the way towards age-related disease and eventual death. They are known as AGE-breakers. If you're a keen student of the healthy life extension community, you'll know of the excitement over alagebrium, also known as ALT-711. This is an early, deliberately designed AGE-breaker that showed real promise in animal studies. Read more about it here:

https://www.fightaging.org/archives/000981.php

Unfortunately, alagebrium didn't do anywhere near as well in human trials. It was designed at the very outset of the biotechnology revolution, with tools and a lack of specific knowledge about AGEs that would already be shocking to today's young chemists. As such, and unfortunately, alagebrium appears to work on AGEs that are much more common in old rats than in old people.

Researchers can do much better today, however. We now know which type of AGE is most common in aged human tissue, and every year it is easier and cheaper to design complex drugs for very specific tasks. Where does the road take us next, beyond alagebrium and towards far more effective AGE-breakers? Find out in the 1000th Fight Aging! post:

https://www.fightaging.org/archives/001000.php

THESIS: DYING TO LIVE FOREVER

Greg McMullen has published his thesis online; he examines that part of the healthy life extension community focused on greatly extending healthy human life span - centuries, not decades, being the first target in their minds. Links to the PDF format document and commentary in the following post:

https://www.fightaging.org/archives/000997.php

Amongst other items of interest, it contains an interview with biomedical gerontologist Aubrey de Grey, an examination of the Immortality Institute community, and thoughts on how myths of mortality interact with present efforts to raise support for healthy life extension research. You should take a look, and see what you think.

As an aside, centuries of healthy life is plausible from a fundamental science point of view; there is no objection in physics to maintaining a complex machine for as long as you care to put in the effort to keep it running. Beyond that fact, there are many examples in nature of systems that are, in effect, immortal until ended by violence or radical change in their ecosphere. We as a species are one of those systems, reliably turning out young children from aged parents:

https://www.fightaging.org/archives/000888.php

The problem with centuries of healthy life is that we do not yet know how to keep our individual machinery running - we need to get started on figuring that out. Whether or not you see centuries of vigor and growth as your goal, all support for healthy life extension has to start at the same place: we need more research, more support and more scientists working on the fact that all our biochemical machinery is slowly failing.

https://www.fightaging.org/archives/2004/11/strategies-for-engineered-negligible-senescence/

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/

Understanding Notch Signaling (October 15 2006)
http://www.nyas.org/ebriefreps/main.asp?intSubsectionID=4321
Via the New York Academy of Sciences, an overview of some of the significance of the Notch signaling pathway: "In addition to its role as a gatekeeper of development, the Notch signaling pathway has been implicated in a number of disorders, including cancer, prion diseases, and multiple sclerosis. Notch's role in these disorders stems from aberrant activation of the pathway. In brain cancer, the Notch signaling pathway sets off the production of proteins that promote unchecked cell renewal. In prion disease, Notch activation causes atrophy of nerve cell dendrites and uncontrolled growth of other brain cells called astrocytes. In multiple sclerosis, Notch sets off an autoimmune attack against the brain via the overproduction of certain immune cells." If you look back in the Fight Aging! archives, you'll find more on the significance of Notch when working with embryonic stem cells. In order to effectively use stem cells of any stripe in more sophisticated therapies, scientists must gain better control over their differentiation and group behavior.

Cytotoxic T-Cells Versus Cancer (October 15 2006)
http://www.newhousenews.com/archive/macpherson101106.html
A Newhouse News article sheds light on the present state of cancer vaccine research and development: an "immunologist's work with the human body's protectors, called cytotoxic T-cells, has led to an increasingly successful effort to develop a vaccine for breast cancer - one that, after injection, would actually eradicate the disease. ... Researchers at Advaxis are using a genetically engineered version of the common bacterium listeria to provoke T-cells to attack cancerous tumors. ... The challenge involved in designing a breast cancer vaccine is convincing our immune system to target the cells of our own body - and cancer cells are part of us - for demolition. With a clear understanding of how the immune system works, we might be in a position to create a vaccine."

Excess Weight and Arthritis (October 14 2006)
http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20061013-08383900-bc-us-arthritis.xml
Via Science Daily, a reminder that excess weight - and the lifestyle needed to maintain it - damages you in all sorts of ways over the long term: "research showed doctors diagnosed arthritis for 31 percent of obese adults and 21 percent of overweight adults said, compared with 16 percent of adults who were within acceptable weight norms ... A quarter of those who were physically inactive said they had doctor-diagnosed arthritis, compared with the roughly 20 percent of adults who were physically active." In addition to the chronic inflammation that comes from aggregations of fat, there's also the matter of exercise: less of it is demonstrably bad, helping put you into a downward spiral of conditions and limitations that both further damage your health and hinder you from leading a more healthy lifestyle.

CR and IGF-1 Signaling (October 14 2006)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17034982
An interesting paper on calorie restriction biochemistry via PubMed: "Both life-long caloric restriction (CR) and the suppression of insulin-like growth factor-1 (IGF-1) signaling reliably extend the mammalian lifespan. The neuroendocrine system, regulated by the hypothalamus, remains the most convincing site of action for both these modes of life extension. Yet, determining whether CR actions are mediated by the modulation of neuroendocrine IGF-1 signaling remains unclear. ... while CR induces greater loss in the total number of cells in the [supraoptic nucleus (SON)] with age, it reduces the degree of age-dependent loss seen in [IGF-1 receptor (IGF-1R)] expressing cells. As a result, when compared to [old ad libitum fed] mice, the SON of [old calorie restricted] mice displays a greater proportion of IGF-1R cells and thus possibly enhanced IGF-1 sensitivity with aging." It's all pretty interesting, but remember that tinkering with metabolism is a dead end road - the gains will be minor and expensive in comparison to other ways forward.

Gene Therapy For Parkinson's (October 13 2006)
http://www.medicalnewstoday.com/medicalnews.php?newsid=53791
Good news from Medical News Today: "CERE-120, a gene therapy product in development for the treatment of Parkinson's disease, was was well tolerated and appeared to reduce symptoms by approximately 40% [as] measured by the Unified Parkinson's Disease Rating Scale (UPDRS) motor "off" score ... CERE-120 is comprised of an adeno-associated virus (AAV) vector carrying the gene for neurturin (NTN), a naturally occurring protein, whose role is to keep dopamine-secreting neurons alive and functioning normally." Promising gene therapy trials are now producing results much like those of promising drug trials: the path of every new, superior technology includes a period of time in which it comes up to par with the best of older technologies. Old-style drugs can't get much better - but gene therapy has hardly even started.

PBS Tissue Engineering Interview (October 13 2006)
http://www.pbs.org/newshour/bb/health/july-dec06/atala_10-11.html
A transcript of an interview with tissue engineer Anthony Atala can be found at PBS: "You know one of the major challenges today in the field of regenerative medicine is the resources that we have available to really bring these technologies together. It takes enormous amounts of, of uh, funds to actually get these tissues to look and act normally and that is just in a laboratory. It takes yet another large investment to be able to bring these tissues on the bench to the bedside. ... I think that there should be a massive regenerative medicine project, a nationwide effort to really try to accelerate these technologies to patients. The issue at hand right now is that the technologies are there. We already know that the potential is there." A good rule to live by: no realistically attainable amount of funding is ever "enough."

Longevity Requires a Cancer Cure (October 12 2006)
http://www.guardian.co.uk/uklatest/story/0,,-6138202,00.html
Via the Guardian, a brief but pointed look at cancer statistics: "The number of cases will go up because there will be more people and cancer patients will live longer, but the chance of contracting cancer will largely stay the same. Currently around one in three people in Britain will be diagnosed with cancer at some point during their lives. Prof Moller's predictions showed that the number of annual cases of cancer in men will go from 111,639 in 2001 to 152,381 in 2020, a rise of 36%." All our work to extend healthy longevity will be for naught without highly effective, widely available, low-cost therapies for cancer. Your chances of developing cancer become ever-greater with each passing year. Fortunately, this is one area in which the funding, public support, patient advocacy and research infrastructure is already in place; those of us who can afford to wait 20 years for a cure should be cautiously optimistic.

On Embryonic Stem Cell Research (October 12 2006)
http://www.jcb.org/cgi/content/full/174/6/743
From the Journal of Cell Biology: "Talk of policy has dominated talk of science for those interested in embryonic stem cell science. But research is continuing, and the advances are making clear why embryonic stem cells [ESCs] are such an important scientific and medical resource. ... To assess the state of the field, we check in with five bench scientists who are pushing embryonic cells to be all that they can be. The projects they are tackling include a survey of what gives an ESC its identity, new attempts at deriving ESCs from [somatic cell nuclear transfer, or therapeutic cloning], perfecting the transformation of ESCs into either oligodendrocytes that make myelin or pancreatic cells that make insulin, and creating an ESC-based model for Alzheimer's disease." ESC research is vital to the end goal of replacing cells lost with age, thus preventing a range of degenerative, fatal conditions.

Speculating On Fat and Dementia (October 11 2006)
http://www.msnbc.msn.com/id/15206566/
From MSNBC, news of another study suggesting that "a heavier weight in middle age may mean a higher risk of dementia later in life. ... It's possible [that] excess fat cells have some direct effect on brain function. For example, some studies suggest the 'hunger' hormone leptin, which is produced by fat cells, plays a role in learning and memory. And although these study participants were in generally good health, disorders like elevated blood pressure and diabetes could act as a bridge between high BMI and poorer cognitive function. Thickening and hardening of the blood vessels supplying the brain can contribute to dementia ... Similarly, diabetes may harm cognition by either leading to artery disease or via direct effects of the hormone insulin on brain cells."

The Damage Done By Patents (October 11 2006)
http://www.the-scientist.com/news/home/25037/
A patent is, in essence, a way to use government force to expand your short-term profits at the expense of everyone else. From this piece at The Scientist: "A narrowing or invalidation of the patents could speed up research, many scientists say. Some researchers complain that the licensing process slows their work down, while others say it is prohibitively expensive. ... It slows things down and sort of sets up an artificial step in the process." A patent is a form of regulation, and regulated industries mean slow progress, expensive goods, and an reduction in competition. Competition is the only incentive process that leads to better, cheaper, more effective products. Industries that depend absolutely on ideas but are largely free of patents - or even copyright in the case of fashion design - are highly dynamic, competitive and profitable. Why, then, do we put up with this nonsense of the few exploiting the many in far more vital industries such as medicine?

Mole-Rats, Thyroid Hormones (October 10 2006)
http://www.eurekalert.org/pub_releases/2006-10/aps-lrh100706.php
Yet more naked mole-rats in this research on thyroid hormone levels and longevity in rodents, via EurekAlert! This one raises more more questions than it answers: "The thyroid gland produces thyroxine (T4) which converts to triiodothyronine (T3) in the presence of iodine. T3 is the active component of T4 and is the key hormone in regulating metabolism ... T4 levels varied significantly between all of the groups, with the shorter-lived groups having higher levels of T4 than longer-lived groups. The mice, for example, had twice as much T4 as the Damara mole-rats and had and three times more than that of the naked mole-rats ... There was also a significant difference in T3 levels between the naked mole-rats and the guinea pigs." To put this in an interesting context, it has been shown that calorie restriction lowers levels of T3. A complicated thing, metabolism. This is why I support efforts to identify and fix cellular damage (easier, more effective) rather than tinkering with metabolic processes (harder, less effective).

Destroying Chronic Infections (October 10 2006)
http://www.newscientist.com/article/dn10264-inflammation-turned-on-to-fight-killer-viruses.html
One main reason your immune system fails with age appears to be that chronic infections by the likes of cytomegalovirus (CMV) cause too many of your immune cells to be - uselessly - specialized. As noted in the New Scientist, researchers are looking into a possible way of clearing these infections from the body: they "studied an acute and chronic meningitis infection in mice, called lymphocytic choriomeningitis virus (LCMV). They discovered that mice with chronic infections had high levels of the inflammatory-damping chemical interleukin-10 (IL-10). When they gave mice with chronic LCMV a drug that blocks the inflammatory-calming action of IL-10, the inflammatory immune response was re-activated. Within a week the mice were healthier. In two weeks, they had cleared the virus completely." Now if this could be turned against CMV early in life, the immune system would look a lot better later on - but a method of cleaning out the uselessly specialized cells would be needed to help those suffering now.

Rate of Living Theory Still Dead (October 09 2006)
http://www.eurekalert.org/pub_releases/2006-10/aps-ed100206.php
Last nails from EurekAlert!: "One early theory, the rate of living theory, held that every organism has a set amount of energy to expend. Once the animal expended that number of calories, the grim reaper was on the doorstep. Over the years, the theory has become much more sophisticated, but metabolic rate and aging have remained linked ... Runner mice that had access to a wheel expended 25% more energy over the course of their lives compared to both the runner group that did not have a wheel and the regular mice ... The rate of living theory would have predicted that the running group that expended more energy would die earlier than the two groups that did not ... This was not the case. There was no difference in life span between the two runner groups, even though one expended more energy." Recall that exercise is demonstrably good for health and resistance to age-related disease.

Naked Mole-Rats Again (October 09 2006)
http://www.newswise.com/articles/view/524122/
More on long-lived naked mole-rats and their ability to shrug off oxidative stress via Newsise: "The researchers next looked at how much damage the oxidation had caused. It is possible, they reasoned, that the mole-rat suffers greater oxidative stress, but its physiology had somehow prevented damage from occurring. The researchers measured oxidative damage in lipids, DNA and proteins and found that naked mole-rats showed much greater levels of damage to each of these biological molecules, in all tissues assayed, when compared to mice. ... All of the classical measures of oxidative stress are higher in the mole-rat. Given that naked mole-rats live an order of magnitude longer than predicted based on their body size, our findings strongly suggest that mechanisms other than attenuated oxidative stress may explain the impressive longevity of this species." A puzzle, and one we humans should be interested in the answer to: oxidative stress causes us serious damage and is one root cause of aging. How are the mole-rats getting away with it?

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