Longevity Meme Newsletter, March 28 2005

March 28 2005

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.



- What Research Is Getting Funded?
- Manipulating Metabolism For Fun and Profit
- Fixing Our Aging Stem Cells
- Understanding and Repairing Mitochondria
- Bigger, Bolder Steps Are Needed
- Discussion
- Latest Healthy Life Extension Headlines


As many of you no doubt know, many promising fields of medical research could have a large impact on aging and our healthy life spans. Few of these fields are getting the funding they deserve. Therein lies the largest problem we face: not that there are technological hurdles to overcome, but that significant funding (private or public) is still absent. What is "significant funding?" Look at cancer research or Alzheimer's research - at least a billion dollars per year. This sort of funding can only appear at the end of a long ramp up in understanding and support, both within the scientific community and amongst the public. Viewed from the highest level, public funding needs the backing of the populace at large and private funding goes to answer the loudest signals from the marketplace of ideas and desires. To see this process in action, just look at what has happened for the field of regenerative medicine and stem cell research over the past few years.

Life expectancy and healthy life span have been slowly growing over the course of the last fifty years of modern medicine. This is the result of tackling individual conditions and diseases as they rise in incidence or are identified and separated out from what is currently lumped together as "degenerative aging." You can find some related comments on this progression at the following pages:


Curing cancer would be a very good thing - that goes without saying. Cancer research continues to lead scientists to a far greater understanding of the way in which our cells work at the molecular and genetic level. Yet curing cancer will not greatly increase life span. Curing heart disease would save many lives each year - yet the people who currently live the longest and healthiest do not generally die from heart disease. Similar points can be made for Alzheimer's, Parkinson's or any other well known age-related condition you care to pick out: cures will not greatly increase the human life span. There will be other, new and more complex degenerative conditions to be identified on the far side of Alzheimer's, or in a world in which no-one dies of diabetes or heart disease.

This approach of tackling conditions as they come to light is where the big money in medical research goes. While it does a great deal of good, it does not lead to meaningful increases in life span. In essence, this is a reflection of the one of the most important divisions in modern medicine - prevention versus cure. We have arrived at a medical system in which cures can be profitable, but preventative medicine is hard to get off the ground. This is as much a result of regulation as it is a mindset; just look at the less regulated supplement, diet and exercise industries to see people making a profit out of what is in essence crude preventative medicine.

As longevity research is becoming more respectable, funding is starting to trickle into areas that may have much more impressive effects on healthy life span. We can look at many of these as forms of preventative medicine - making alterations or repairs that will delay the onset of age-related conditions, or delay the onset of cellular and genetic damage. Currently, research funding is still fairly meager, but it is enough to see a fair pace of progress.


Firstly, we have the manipulation of metabolism. The free radical theory of aging and its descendants point the finger of blame at reactive byproducts of our metabolic processes; these byproducts damage our cells and DNA. However, it is becoming increasingly clear that metabolic processes can be fine tuned in a number of ways - this realization is one of the fruits of calorie restriction research. The search for calorie restriction mimetic drugs - that can replicate the large extensions in healthy life span seen in mice - is probably the most well known of current efforts to change our metabolic processes for the better.


It is worth noting that this field is comparatively well funded because it can be spun as a search for cures for conditions like diabetes. While most in the gerontological community are quite aware of the potential of the work of David Sinclair and Sirtris Pharmaceuticals to extend healthy life span, for example, you won't find any mention of such on their website.


This shows that while longevity research is becoming more respectable, there is still a way to go yet before the funding floodgates open for initiatives explicitly aimed at preventative therapies for the aging process. Still, an example of another approach to metabolic manipulation can be found in the healthy life extension news for the past week:



Can aging stem cells be restored to youthful vigor and thus give an old body the power to heal itself once more? Would this have a large effect on healthy life span? These are good questions, and enough money is flowing into stem cell research that we are likely to see answers in the years ahead. You might recall that recent work in mice demonstrates that simple chemical cues may be enough to convince older stem cells to get to work once more:


Of course, we don't yet know what those cues are, or what the side effects are of triggering them in older bodies. Nor do we know how much of age-related degeneration can be blamed on the decline in our stem cells, although tantalizing clues keep surfacing in the most unexpected places, such as the graying of our hair and its link to skin cancer:



There is a very definite link between mitochondria, the powerhouses of our cells, and aging. Is accumulated damage to mitochondrial DNA an important root cause of aging? Is aging a form of ongoing power failure in our cells? That wouldn't be a bad bet to take right now:


This work also ties into metabolic studies; the mitochondrial production of free radicals and rate of damage to mitochondrial DNA forms a complex, interesting feedback loop. A number of research groups are currently taking a closer look at these processes and at ways to manipulate, protect and ultimately repair mitochondrial DNA. See this Fight Aging! post from last year for an example:



The bottom line is that most of us reading this newsletter today are not going to greatly benefit from the "one cure at a time" approach to medicine. We won't suffer the horrible effects of Alzheimer's, nor will we die from heart disease. Cancer will most likely be a controllable, chronic condition 20 years from now. Yet we won't be living much longer overall as a result of those advances - they do not address the underlying cause of aging and age-related death.

A real sea change must come about in the way in which aging is addressed by the research community, not to mention the level of funding put into longevity research. We are very close - a matter of decades - from being able to greatly increase the healthy human life span; by decades initially, and far more subsequently. You can find more details on how this could happen at Aubrey de Grey's Strategies for Negligible Engineered Senescence (SENS) website:


Everything else aside, the funding must be there. That $1 billion per year for directly longevity research has to happen. Making it happen is up to all of us - we make the future through our actions and expressing our wishes to those who direct investments. So stand up today and do something for the future of medical research and 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



Stem Cell Polling From CAMR (March 27 2005)
The latest poll from the Coalition for the Advancement of Medical Research shows strong support for embryonic stem cell research and therapeutic cloning - especially once the goals, such as curing common age-related conditions, are explained. "59% strongly or somewhat favored [this] research, and only 33% opposed or strongly opposed it. But after a brief description of the research was read, the percentage in favor increased to 68% compared to only 28% opposed. A question regarding the use of [therapeutic cloning] found that 60% strongly or somewhat favored the research, and only 35% somewhat or strongly opposed it. However, after a more detailed description [was read], the more respondents favored the research, 72% compared with only 23% opposed."

Tuning The Metabolic Engine (March 27 2005)
Funded longevity research today is largely based on determining ways to "fine-tune" our metabolic processes - calorie restriction mimetics such as those sought by Sirtris are a good example. The Scotsman looks at another methodology: "We found making the metabolism in cells less efficient meant more oxygen was consumed and fewer free radicals were produced. In effect, a pharmaceutical target would pump up the metabolic rate to reduce the free radical production. Because free radicals also play a role in causing cancer and other diseases, reducing the number produced can not only increase the length of time someone lives, but increase their healthy lifespan." This sort of work is not expected to bring more than ten or twenty extra healthy years, however - going beyond this requires better technology.

Rejuvenating Stem Cells (March 26 2005)
(From Haaretz). Scientists are looking to the rejuvenation of aging stem cells in the body: "The big revolution will come when stem cells can be used to stop the aging process. Five years ago, when scientists were talking about 'stopping the biological clock,' it sounded like science fiction. ... scientists took an old mouse and a young mouse and joined their blood systems. They found that the exposure caused the stem cells of the elderly mouse to be renewed ... The search for substances that will cause our stem cells to be rejuvenated could be one of the big revolutions of our times." There are many caveats associated with this line of research - we have no idea whether or not rejuvenating stem cells would have a large effect on the aging process, for example - but it certainly shouldn't be dismissed.

The Hype Of Growth Hormones (March 26 2005)
The Times is running a very sane article on the hype surrounding growth hormones in the "anti-aging" marketplace. "Taking hormones to hold back the years is based on a myth. And, for people who have no medical need for hormone supplementation, swallowing the dream could hold fatal risks. ... Extensive work from Scandinavia has shown that injecting the hormone does not restore muscle mass or fitness to the elderly." Unlike calorie restriction, there simply isn't an overwhelming weight of science and knowledge backing the use of hormones - and most of the widely available (and useless) products are sold by the shady, disreputable end of the "anti-aging" industry. Buyer beware.

More Tissue Engineering Timelines (March 25 2005)
The conventional wisdom on the future of tissue engineering is echoed in the People's Daily Online: "Part of human tissues such as bone, muscle, blood vessel, or even nerve can be 'batch-produced' in another 10 or 15 years said Doctor Cui Zhanfeng ... Cui said that despite of some explorations there would be many [technically] difficult problems before realizing batch production of human tissues. For example the sources of stem cells, the material for support, bioreactor, how to enlarge tissues in industrialized production as well as any rejections caused by implanting. They are involved in many areas of engineering, medical science and materials."

New Heart Stem Cell Therapy Trial Starts (March 25 2005)
EurekAlert reports that a new study on the use of adult stem cells to repair heart damage is underway in the US. "Previous research in animals showed that when adult stem cells were injected directly into the heart muscle, heart function was restored to its original condition within two months. [Last November] the Hopkins team showed, again in animal studies, that more than 75 percent of dead scar tissue disappeared after therapy, which produced mostly healthy, normal-looking heart tissue and left only a small trace of the heart attack. The Phase I study is being conducted at Hopkins, with support from Baltimore-based Osiris Therapeutics, which developed the stem cell product. The study will involve 48 adults who have had their first heart attack within 10 days of enrollment in the trial."

Update On Indian Stem Cell Work (March 24 2005)
From Express India, an update on progress in trials and research in that country. "The premier medical institute in the country is all set to prove to the world the efficacy of its stem cell therapy conducted over the last 18 months on heart patients ... In our study we used this therapy on 33 patients and all of them are showing positive results. ... Researchers at AIIMS have also conducted some pilot studies for use of stem cells in diabetics and now plan to inject these cells directly into pancreatic arteries of these patients." Indian scientists are optimistic about the future: "For future research, we are looking at all areas - diabetes, muscular dystrophy, cerebral palsy, other neurological disorders and Parkinson's disease. The residual damage after stroke too can be minimised by injecting stem cells."

Stem Cells, Scaffolds, Three Dimensions (March 24 2005)
Science Daily reports on the continuing realization that moving into the third dimension makes a big difference to stem cell research: "In conventional cell cultures, cells usually grow as flat deposits bathed in growth medium. ... Specific genes, proteins and hormones normally produced by healthy cells are often absent in two-dimensional colonies. ... Researchers here have used a new microscopic, three-dimensional scaffolding to coax mouse stem cells to transform themselves into fat cells, and then to function identically to how fat cells naturally do in the body. ... This discovery offers hope of a new approach to growing fat tissue for use in breast reconstruction surgery and other clinical needs, and may even be important for curing [age-related] diabetes."

More On Skin Aging (March 23 2005)
Despite being obscured by the nonsense put out by the "anti-aging" marketplace, serious research into how our skin ages is taking place - just as for aging in other important organs. You may recall that we mentioned work on lost elasticity in skin last year, for example. A New Scientist article provides some details on continuing research into how and why our skin ages: "Wrinkles and the leathery feel of old skin are thought to result from changes in the dermis, the deepest layer of skin. This becomes fibrous, making the skin less elastic ... changes may also be taking place in the epithelial cells above the dermis." We can hope that this won't immediately be trivialized by the quick buck contingent at Revlon et al, as this sort of work has important implications for treating a wide range of serious age-related disorders.

Immortality Institute Essay Contest (March 23 2005)
The Immortality Institute has launched an essay contest: winning essays will be considered for inclusion in the next Institute book. The topic for consideration is oblivion: "In Lamont's The Illusion of Immortality the term immortality refers to existence of a soul in an afterlife. The illusion to which Lamont refers is that there likely does not exist an immortal soul. ... the term immortality as used by scientists today mainly refers to agelessness of an entity or organism. The Immortality Institute prefers to use the term physical immortality as to mean the 'concept of existing for a potentially infinite or indeterminate length of time.' How does one come to terms with the seemingly inescapable problem of oblivion after ones own death? In the 70 years since Lomont first published his work, why has so little been written about the problem of oblivion after death? Can science prove or disprove oblivion after death?"

Understanding Alzheimer's (March 22 2005)
(From Science Daily). The vast sums of money invested in Alzheimer's research are paying off as capabilities and tools improve. "Researchers at UC Irvine have identified a trigger at the molecular level that marks the onset of memory decline ... The trigger is a protein called "beta amyloid" that accumulates within neurons ... Although several researchers have studied the association between beta amyloid and memory, the UCI research team is the first to identify that early beta amyloid accumulation within neurons is the trigger for the onset of memory decline in Alzheimer's." As understanding of biochemical processes increase, so too do the chances of near-term therapies or even a cure. Preventing and repairing neurodegenerative conditions is especially important to the future of healthy life extension.

State Funding And Stem Cell Research (March 22 2005)
A rather wonkish piece from Chemical & Engineering News looks at likely prospects for the future of public funding of stem cell research in the US. As is true of most such articles, private funding - the majority of medical research funding over the long term - is not discussed. "The genesis of this complex picture is a federal policy that only allows federal funding of research on [human embryonic stem cell] lines derived before Aug. 9, 2001. Of the initial 78 lines covered by this policy, only 22 lines are currently viable. This number is a sharp contrast to the more than 150 lines that have been derived since the policy was announced and are prohibited from study with federal funds." In fact, none of those 22 lines are viable for research - all are contaminated.

More On Adult Stem Cell Progress (March 21 2005)
Progress is slowly being made in controlling stem cell differentiation in both embryonic and adult stem cells. This is key to the reliable use of stem cells in regenerative therapies for age-related and other conditions. The Australian reports on recently published work: "Our experiments have shown adult stem cells isolated from the olfactory mucosa have the ability to develop into many different cell types if they are given the right chemical or cellular environment ... New nerve cells, glial cells, liver cells, heart cells, muscle cells -- all were grown in a dish from stem cells from the human nose." A methodology for obtaining and differentiating multipotent, easily extracted adult stem cells would certainly speed up many lines of research.

Latest Ellison Foundation Grants (March 21 2005)
One of the most recent grants provided by the Ellison Medical Foundation went to biologist Alexander Varshavsky "to conduct a systematic investigation of the genetics and biochemistry of aging. ... Every cell contains within it a molecular machine to eventually destroy its own proteins, he notes ... Detailed understanding of these protein-destruction pathways will have a profound impact on the practice of medicine, because all kinds of things that go wrong with us, from cancer and infectious diseases, to neurodegenerative syndromes and even normal aging, have a lot to do with either inherent imperfections of the ubiquitin system, or with an overt damage to it in a specific disease ... His aim is to discover the molecular circuits that contribute to normal aging, and also to see whether some of the alterations that he plans to introduce could slow down the aging process."



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