Longevity Meme Newsletter, August 13 2007

August 13 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.



- Longevity Mutations Keep Rolling In
- What Will Be Accomplished By 2030?
- Discussion
- Latest Healthy Life Extension Headlines


Biomolecular researchers have been hitting their stride in recent years. At least half a dozen methodologies are now demonstrated to extend healthy life span in mice by 30-40%, all based on tweaking the operation of core components or systems of metabolism. Here's the latest, another single gene alteration:


"Genetic deletion in mice of pregnancy-associated plasma protein A (PAPP-A), a recently identified metalloproteinase in the insulin-like growth factor system, extends by 30-40% both mean and maximum lifespan with no reduction in food intake or secondary endocrine abnormalities. Furthermore, these mice have markedly reduced incidence of spontaneous tumors."

It is interesting to note that divergent genetic engineering and other means of altering metabolic processes seem to top out at around 30-40% increased longevity in mice, just like calorie restriction - so far, at least. It does tend to suggest a commonality of mechanisms at the base of it all, however.

The insulin-like growth factor system mentioned above is of great interest to a range of scientists. It is also of great complexity and reach within our biochemistry - almost everything that takes place in your body is affected by it:


While reading though that reference, appreciate just how much time and funding it has taken to understand even the outline of human metabolic biochemistry. It's worth keeping this thought in mind:


"The scientists doing this [metabolic work] will swear up and down that aging doesn't have a chance in hell of being fixed in any of our lifetimes, because they know just how complicated metabolism is, and fixing metabolism is the only thing that fits in their conception as being a fix for aging."

But we don't have to re-engineer metabolism; we don't have to take on that level of complexity. Rather, the scientific community could work on the more efficient and direct route to repair the damage caused by metabolism instead, as outlined in the following Fight Aging! post:



How far will we have driven the medical science of longevity by 2030? Progress depends entirely on the level of support we're all willing to put in, but that never stopped people from speculating:


"Achieving three times or more progress in longevity from 2007 to 2030 versus 1984 to 2007 seems very achievable. This will be from public health improvements, disease cures or treatments, lifestyle improvements (from behavior or with medical assistance) and success from direct progress against the processes of aging. This would mean going from a life extension increase of 0.1 to 0.2 years each year to 0.5 years.

"Some folk in the systems biology field project a 10 to 20 year increase in life expectancy over the next 20 years. The Longevity Dividend folk are aiming for 7 years over a similar timeframe, and the actuaries are debating models that fall within these ranges. Aubrey de Grey, of course, makes the case that indefinite healthy life span in mice, maintained through repair technologies, has a good chance of success 20 years after large-scale funding is initiated for such a project.

"Those in the know agree that more healthy life is possible and plausible, but disagree on how much and how exactly it will be attained. Certainly it will require support and understanding, regardless of the methodology that wins out in the end; science develops to the degree that people desire technology to achieve their ends, and are therefore willing to fund research."


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



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/

Werner's Syndrome, Progeria and Cellular Senescence (August 10 2007)
Chris Patil looks at recent attempts to find common mechanisms in accelerated aging disorders: "some conditions are best thought of 'segmental' progerias (in that they model aging only in specific organs or cell types), whereas others model the natural aging process very closely in the majority of tissues. Chief among the latter are Werner's Syndrome (WS) and Hutchinson-Gilford Progeria Syndrome (HGPS). The underlying mutation in the two diseases are quite different: WS is due to a mutation in a DNA helicase involved in repair, whereas HGPS is caused by a dominant mutation in lamin A/C, which is critical to nuclear structure (and consequently in gene regulation). While the diseases have distinct phenotypes and ages of onset, they are both widely considered good models of accelerated aging. What, if anything, is the common currency between the two? ... Cox and Faragher argue that premature cellular senescence is likely to be important in both WS and HGPS ... According to this model, senescence (which permanently growth-arrests old and damaged cells) prevents individual cells from forming tumors, but persistent senescent cells embark on a highly anti-social program of gene expression that can [damage] surrounding tissues and may contribute to age-related decline in tissue function."

Aging as a Computational Problem (August 10 2007)
Biology is information, thus all human interaction with biology is a computational challenge - and so is the quest to defeat aging. The future of biotechnology is entwined with the future of computational power: simulations, complexity management in therapies and tools, and much more. From TechNewsWorld: "while the scientific community knows how to study aging much better than a few decades ago, the idea that aging is a disease is still very contentious. That's because, if aging is a disease instead of a normal phase of life, that implies that something must be done to stop it -- politically a lost cause in many cases ... the best and brightest ought to be looking for ways to fight age-induced disease, and one powerful weapon in this quest is computer-based biological modeling. Computer scientists can make a huge impact on this area of inquiry and should work toward partnering with scientists ... Aubrey de Grey, a well-known leader of the anti-aging movement, started out in computer science and is now applying that knowledge to biology. His example should be emulated. ... Whether or not federal grant makers like it, aging research and practitioners are moving forward. ... The idea that aging is a disease will someday be as common as an online game. In the meantime, important advances in fighting age-related disease are in the works and computer scientists are playing an important role. That role should be allowed to expand, without political interference."

Methuselah Foundation Science Team Expands (August 09 2007)
As the Methuselah Foundation continues to raise funds for the Strategies for Engineered Negligible Senescence (SENS) research, more young turks will be joining the science group: "Ben Zealley is the newest member of the Methuselah Foundation's scientific team, having joined this summer after completing his degree at Cambridge. He will be working with Dr. de Grey and Michael Rae to expand SENS and develop potential avenues of research. ... I have been interested in the human aging process - and Dr. de Grey's approach to it - for many years, so I'm very much looking forward to being able to work full-time on SENS at last. I'm particularly interested in therapies with rapidly-visible or immediate benefits, since these will be instrumental in swaying public opinion towards the concept of aging as a disease open to effective treatment. Once that's been achieved, the battle will be halfway won!" Funding, time and a group of enthusiastic biomedical researchers will get you a long way - it's good to see SENS ever more on the move.

Why Aging Muscles Heal Poorly (August 09 2007)
More on the fading capacity of muscle stem cells with age via ScienceDaily: "as we age, the lines of communication to the stem cells of our muscles deteriorate and, without the full instructions, it takes longer for injured muscles to heal. Even then, the repairs aren't as good. But now that the researchers have uncovered the conduit that conveys the work orders to muscle stem cells, that knowledge could open the door to new therapies for injuries in a host of different tissues. The key to the whole process is Wnt, a protein traditionally thought to help promote maintenance and proliferation of stem cells in many tissues. But in this instance, Wnt appears to block proper communication. ... the ability of muscle stem cells to regenerate tissue depends on the age of the cells' environment (including the age of the blood supplying the tissue), not the age of the stem cell. Although Rando's research focused on the repair of acute trauma to muscles, he suspects that the same sort of problem arises on a lesser scale in repairing damage that results from the normal wear and tear of aging." I've been watching this research over the past couple of years - there are great opportunities there, a chance to take a bite out of degenerative aging, as is true of so much of modern biomedicine.

Towards An Age Without Metastasis (August 08 2007)
Cancer without metastasis would be that much less threatening of an age-related condition. One effect of ever increasing knowledge of cellular processes will be the elimination of cancer's spread. From EurekAlert!: "For a cell such as a cancer cell to migrate, it first must detach itself from neighboring cells and the intercellular material to which it is anchored. Before it can do this, it receives an order from outside the cell saying: 'prepare to move.' This signal takes the form of a substance called a growth factor ... the team mapped all of the genetic changes that take place in the cell after the growth factor signal is received. As they sifted through the enormous amount of data they received, including details on every protein level that went up or down, one family of proteins stood out. Tensins, as they're are called, are proteins that stabilize the cell structure. ... the growth factor directly influences levels of both [tensin] proteins, and that these, in turn, control the cells' ability to migrate. Blocking production of the short tensin protein kept cells in their place, while overproduction of this protein plug increased their migration." Researchers are in the early stages of evaluating compounds to manipulate tensins; if they work out, tensin inhibitors would be another armament for anti-cancer dendrimer technology.

The Engineering Approach Versus Fixing Metabolism (August 08 2007)
You'll find a great discussion over at the Immortality Institute forums on the difference between the engineering approach to repairing aging and the metabolic tinkering presently favored by the mainstream: "metabolism is so ridiculously complicated that it could take centuries use such a strategy to achieve negligible senescence in humans, and even then, the damage that you already have wouldn't go away. Research into repairing the damage, rather than slowing it's accumulation, is far more logical. If you can repair the damage once, you can do it again and again. ... The scientists doing this [metabolic work] will swear up and down that aging doesn't have a chance in hell of being fixed in any of our lifetimes, because they know just how complicated metabolism is, and fixing metabolism is the only thing that fits in their conception as being a fix for aging. ... Repairing the damage is massively more beneficial than slowing down aging. Slowing down aging leaves the assumption that natural death related to aging is still inevitable. However, through repair mechanisms, as long as there's a will to repair, you could technically continue to repair for as long as possible. And as technology becomes more advanced, the gaps between the periods required for repair will become longer and longer. It's a win-win in both cases."

Watch the Stem Cell Infrastructure Grow (August 07 2007)
The real pace of progress can be seen in improvements in infrastructure - the health of a field in the next decade can be gleaned from the work of the toolmakers today. In regenerative medicine, the tools are improving markedly from year to year, as illustrated by this release from Newswise: "Previously, the system to grow and isolate neurons was very messy and it was unknown whether those neurons were functioning. We're excited because we have been able to purify so many more neurons out of the cell culture and they were, surprisingly, healthy enough to form synapses. These cells will be excellent for doing gene expression studies and biochemical and protein analyses ... The large number of pure neurons produced will allow Sun and her team to study their biological form and structure, the genes they express, the development of synapses and the electric and chemical communication activities within the synapse network. ... We will be able to study the cellular properties of neurons in a very defined way that will maybe tell us what goes wrong in diseases such as Alzheimer's and Parkinson's. We're currently creating many models of human neurological diseases that may provide the answers we're looking for."

Aging and Bacteria in the Body (August 07 2007)
Researchers seek to understand the mechanisms of the complex biological machinery that makes up a human with the aim of extending healthy life by reducing wear and tear. We shouldn't forget, however, that this machinery includes a large and significant bacterial component. "humans and some bacteria are known to have mutually beneficial relationships. People gain nutrients and energy with the aid of bacteria, and the microbes are provided with a buffered environment, carbohydrates, and other nutrients ... Since immune function is impaired with age, it might be expected that 'bacterial load' would increase or be otherwise altered as people grow older. Indeed, studies have found shifts in humans' intestinal bacteria with age and evidence that bacteria may blossom in the prostate and other organs of the elderly. To explore the consequences of such changes in bacteria with age in greater detail, the researchers looked to flies." You might recall that calorie restriction has an impact on bacteria in the body - as it seems to have an impact on almost everything that can be linked to aging.

The Voldemorte Fallacy (August 06 2007)
We almost made it through without what seems to be the obligatory reference, but fell at the last hurdle. Via the IEET: "here is the essence of the Voldemort Fallacy: the notion that seeking longevity beyond that which is 'naturally' granted is somehow intrinsically harmful - even if it doesn't look that way at first, and even if harm itself is not the life-extensionist's goal. Some of the conversations I've been involved in on the subject of longevity have been with people who seem to have the idea that the mere desire for personal longevity will somehow indirectly harm others. This, to me, seems to be the result of a particular brand of superstitious thinking - one that is heavily reinforced by literary portrayals of longevity-seekers. Voldemort's direct harm to others can perhaps be seen as a metaphor for the indirect harm that longevity-seeking is often assumed to perpetrate. Nobody really knows what sorts of evils might come about if people could live as long as they liked, but many people assume that evils must be there regardless, and that it takes a certain kind of weakness of character not to passively accept one's demise. ... The hope for a very long life is no different, as far as I'm concerned, from the hope that I will wake up tomorrow morning. The question, 'Why live?' is best responded to by the question, 'Why not live?' It isn't all that complicated."

Interfering in the Mechanisms of Alzheimer's (August 06 2007)
The modern form of drug design is to identify a biochemical mechanism and design a compound to safely interfere in its progression. An example of the type can be found at ScienceDaily: "Alzheimer's is linked to the build up of amyloid protein which eventually forms 'senile plaques'. The amyloid protein inflicts damage by interacting with an enzyme called ABAD (Amyloid Beta Alcohol Dehydrogenase) and releasing toxic substances which kill brain cells. ... Alzheimer's sufferers produce too much amyloid and ABAD in their brains. Based on our knowledge of ABAD, we produced an inhibitor that can prevent amyloid attaching to it in a living model. We have shown that it is possible to reverse some of the signs associated with Alzheimer's disease. The work is now being continued to try and refine the inhibitor into a potential drug. Our research holds a possible key for the treatment of Alzheimer's disease, particularly in its early stages." Increasing knowledge of our biochemistry opens the field to a wide range of approaches for any particular medical condition: diversity and competition is good.



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