Longevity Meme Newsletter, June 29 2009

June 29 2009

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.



- An Example of How Research Proceeds
- Aging Ingrained in the Human Condition
- The Singularity's Time in the Sun
- Help Investigate Laser Ablation of Lipofuscin
- Discussion
- Latest Healthy Life Extension Headlines


How do researchers go about deciphering the very complex mechanisms of our cells and our metabolism? Here is an illustrative example of one methodology:


"If the cell is a machine, then the biotechnology revolution has provided scientist-mechanics with wrenches to pull out cogs and screwdrivers to force the settings on inner switches. It has also bequeathed reams of disordered notes from a thousand other mechanics, and from all this sense and understanding has to eventually emerge. So how do you find out what does what in a cell, and by extension in the entire organism that the cell belongs to? Pulling out pieces to see what they were needed for isn't such a bad strategy, especially guided by educated guesswork and related discoveries made by many other engineers. Good educated guesswork is very possible these days, and the cost of chasing down a dead end (in time and money) is falling all the time - it makes sense to explore and take risks."


Why, in world of exercise and health fads, of fitness and a vast market of "anti-aging" snake oil, is it a challenge to create greater support for the development of biotechnology that can reverse aging?


"[Every story contains] shards of what has been the human condition for as long as there have been humans - the story of the fall and the golden age beforehand enacted in a single lifetime, over and over again. We were young, and then we were not, and then we suffered until we died. This human condition is so ingrained in our myths, our histories, and our culture that we live and breathe it every moment that we fail to think differently. We are all caged by our formative years in more ways than we'd like, and our formative years were those in which we learned to accept aging, suffering, and death as the way of things. It's only later that some few learn how to rebel against what the majority consider set in stone, never to be challenged."


Nothing in the laws of physics prevents a golden future of amazing technologies, the technological singularity enabled by exponentially expanding computing power and capabilities in biotechnology. The question is when it will happen: soon enough for us to benefit from?


"Are we going to see a very steep uptrend in new technologies enabled by biotechnology and computing power? If present exponential trends in the amount of data that can be organized and manipulated continue then we should expect such things as emulated minds, near-complete control over our biochemistry, and molecular manufacturing to exist in the 2040s. The nature of an exponential curve in progress is to produce surprise: growth looks linear for a while, and then all of a sudden an explosion of progress occurs.

"[But] you shouldn't be dazzled. The future is far from certain, as it is still being built. The trends look very promising, but are by no means a guarantee that the applications of future technology actually built within our lifetimes will include the ones you and I desire. I'm sure we can all rattle off a list of large scale projects that have been possible for decades but never happened - colonizing the oceans, irrigating the Sahara, and so forth. The end of aging and radical life extension in particular will only happen if enough people understand that it can happen, and from that a large enough research and development community is generated to make it happen. Wishful thinking only works when someone, somewhere is getting the job done."


As I mentioned last week, the Immortality Institute is funding an $8000 matching grant for initial validation of the use of pulsed laser light to break down lipofuscin in the body, and thereby defeat its contribution to the damage of aging:


This is a good example of the consequences of falling costs in biotechnology: small groups of interested people can fund potentially important early stage research, because some of that research just doesn't cost very much anymore. The work will be carried out under the auspices of SENS Foundation, who already fund another line of research into removing unwanted and damaging metabolic byproducts like lipofuscin from the body.


So put a few dollars into the fund, and know that you're making a good investment: both in this specific research, and in a process for funding early stage work that I think needs become more widespread.


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!




Towards Engineering and Adjusting the Immune System (June 26 2009)
This ScienceDaily release gives some insight into how we might manipulate and repair our aging immune systems in the near future: "During their development in the thymus gland, a kind of 'T-cell school', every T-cell is fitted out with its own personal receptor. The diversity of these receptors allows the immune system to respond to nearly all pathogens. Since T-cell receptors are all randomly constructed, there is also a constant production of T-cells in the thymus that may recognize and attack the body's own structures. ... Most of these dangerous autoreactive T-cells, though, are sorted out in a screening process before they leave the thymus ... But not all autoreactive T-cells are driven to cell death. Some of them are 'reeducated' into so-called regulatory T-cells. While these still possess a T-cell receptor that targets the body's own structures, they have been reprogrammed during their development in the thymus so that they can no longer cause any damage. In fact, it is [quite the opposite]. ... They even keep other nearby errant T -cells under control. This is why the mechanisms for the creation of regulatory T-cells are of enormous practical interest. Deciphering these processes could lead to new therapeutic approaches for autoimmune diseases such as multiple sclerosis, rheumatic arthritis and type-1 diabetes, which are triggered by autoreactive T-cells."

Near 100% Efficiency in Targeting Cells (June 26 2009)
Being able to target very specific cell populations by their distinctive surface chemistry is fundamental to the next generation of medical technologies: "It is now possible to engineer tiny containers the size of a virus to deliver drugs and other materials with almost 100 percent efficiency to targeted cells in the bloodstream. ... We can introduce just about any drug or genetic material that can be encapsulated, and it is delivered to any circulating cells that are specifically targeted ... The technique involves filling the tiny lipid containers, or nanoscale capsules, with a molecular cargo and coating the capsules with adhesive proteins called selectins that specifically bind to target cells. A shunt coated with the capsules is then inserted between a vein and an artery. Much as burrs attach to clothing in a field, the selectin-coated capsules adhere to targeted cells in the bloodstream. ... [For example], metastasizing cancer cells circulating in the blood stream can stick to selectin-coated devices containing a second protein that programs cancer cells to self-destruct."

PAPPA, Mouse Longevity, and the Thymus (June 25 2009)
Researchers here investigate the effects of a mouse longevity gene, and see that it promotes a better functioning thymus and immune system in old age: "Pregnancy-associated plasma protein A (PAPPA) is a metalloproteinase that controls the tissue availability of insulin-like growth factor (IGF). ... deletion of PAPPA in mice leads to lifespan extension. ... Whereas wild-type mice exhibit classic age-dependent thymic atrophy, 18-month-old PAPPA(-/-) mice maintain [a thymus] densely populated by [thymocytes] that are capable of differentiating into single-positive CD4 and CD8 T cells. ... PAPPA(-/-) mice have an overall larger pool of naive T cells ... old PAPPA(-/-) mice have significantly lower prevalence of [T cell forms] known to inhibit T cell activation with normal aging. ... These data suggest [a relationship between IGF and the immune system in healthy longevity]. Controlling the availability of IGF in the thymus by targeted manipulation of PAPPA could be a way to [maintain the immune system during] aging." Reversing the decline of the aging immune system is an important step in prolonging healthy life; the more potential strategies on the table, the better off we are.

Early Benefits of Progress Towards Bioengineered Organs (June 25 2009)
For a field to move efficiently towards its end goal, there has to be some money-making application for early results and partial advances. Here's a look at early applications of work towards artificial bioengineered organs: "Our artificial organ systems are aimed at offering an alternative to animal experiments ... Particularly as humans and animals have different metabolisms. 30 per cent of all side effects come to light in clinical trials ... The special feature, in our liver model for example, is a functioning system of blood vessels. This creates a natural environment for cells. We don't build artificial blood vessels for this, but use existing ones - from a piece of pig's intestine. ... All of the pig cells are removed, but the blood vessels are preserved. Human cells are then seeded onto this structure - hepatocytes, which, as in the body, are responsible for transforming and breaking down drugs, and endothelial cells, which act as a barrier between blood and tissue cells. ... The researchers established that the cells work in a similar way to those in the body. They detoxify, break down drugs and build up proteins. These are important pre-conditions for drug tests or transplants, as the effect of a substance can change when transformed or broken down - many drugs are only metabolized into their therapeutic active form in the liver, while others can develop poisonous substances."

The Breadth of Possible Ways to Manipulate Cells (June 24 2009)
Much of medicine might be thought of, crudely, as the quest to control our cells - to influence their actions and alter their mechanisms to obtain beneficial results. Use of chemicals is the predominant methodology, but it's not the only path forward, as is illustrated here: "Many patients spontaneously recover some function in the weeks and months after suffering a stroke, as their brains reorganize to compensate for the damaged area. Scientists are searching for ways to both boost and focus this innate plasticity, thus improving neural repair. Electrical activity is one option under study: electrical current applied to the brain can modulate brain-cell activity - a crucial component of neural remodeling. ... A week after the start of the experiment, patients given the real treatment performed much better on a number of motor tests [than] those who received the fake treatment, improving by about 12 to 15 percent versus about 3 to 5 percent." This is analogous to early drug development: discovery by experiment, crude usage and small benefits. But we could envisage a line of science that made much more precise use of electromagnetic stimulation in concert with the new tools and knowledge of biotechnology. Would it be practical and competitive with other forms of medicine? Maybe, maybe not. But a great breadth of methodologies in research is the best sign that progress lies ahead.

Exercise: Beneficial Even in Flies (June 24 2009)
The weight of evidence indicates exercise to be beneficial to healthy longevity. This would be expected in most species for much the same evolutionary reasons that calorie restriction extends longevity in almost all species. But how do you test that? "Declining mobility is a major concern, as well as a major source of health care costs, among the elderly population. Lack of mobility is a primary cause of entry into managed care facilities, and a contributing factor to the frequency of damaging falls. Exercise-based therapies have shown great promise in sustaining mobility in elderly patients, as well as in rodent models. ... Here, we describe the first exercise-training paradigm in an invertebrate genetic model system. Flies are exercised by a mechanized platform, known as the Power Tower ... When young flies are subjected to a carefully controlled, ramped paradigm of exercise-training, they display significant reduction in age-related decline in mobility and cardiac performance. Fly lines with improved mitochondrial efficiency display some of the phenotypes observed in wild-type exercised flies. ... The development of an exercise-training model in Drosophila melanogaster opens the way to direct testing of single-gene based genetic therapies for improved mobility in aged animals, as well as unbiased genetic screens for loci involved in the changing response to exercise during aging."

Variations in Human Response to Calorie Restriction (June 23 2009)
This open access paper uses historical data to argue that differences in human mitochondrial DNA (mtDNA) lead to differing health and longevity benefits in response to calorie restriction: "We chose to focus on haplogroup H, which is one of the more recent haplogroups, but also now the most prevalent European mtDNA haplogroup, and compare historical longevity in closely related haplogroup U individuals under extremes of caloric intake. ... The human population has undergone dramatic shifts in caloric intake during different time periods throughout the last 200 years. ... We see an expected general increase in longevity during the 20th century in both haplogroups. Before 1920 there is no significant difference between the longevity of individuals in haplogroup H and U. During the caloric restriction of the Great Depression, 1920-1940, haplogroup H shows significant increase in longevity compared to haplogroup U [with a] mean difference [of] 2.6 years." A very clever analysis; the researchers go on to use computer modeling to theorize on how a specific single nucleotide polymorphism difference between the haplogroups produces this longevity difference.

The Very Near Term of Stem Cell Applications (June 23 2009)
While very interesting advances are taking place in stem cell laboratories, the immediate applications of stem cells to therapy largely involve transplants. So newly discovered sources of stem cells for transplant are likely to be employed for some years to come. Here, ScienceDaily notes the researchers have found "a new avenue for harvesting stem cells from a woman's placenta, or more specifically the discarded placentas of healthy newborns. The study also finds there are far more stem cells in placentas than in umbilical cord blood, and they can be safely extracted for transplantation. Furthermore, it is highly likely that placental stem cells, like umbilical cord blood and bone marrow stem cells, can be used to cure chronic blood-related disorders such as sickle cell disease, thalassemia, and leukemia. ... The greater supply of stem cells in placentas will likely increase the chance that an HLA (human leukocyte antigen) matched unit of stem cells engrafts, making stem cell transplants available to more people. The more stem cells, the bigger the chance of success."

AMA on Hormone Therapies (June 22 2009)
People should be free to do stupid things with their own property, including their own bodies. Similarly people should be free to persuade, catcall, and debate when dumb courses of action are undertaken by others. Here, the American Medical Association (AMA) reminds us of the present state of scientific knowledge on hormone therapies: "Despite the widespread promotion of hormones as anti-aging agents by for-profit Web sites, anti-aging clinics and compounding pharmacies, the scientific evidence to support these claims is lacking ... People want a fountain of youth, and it doesn't exist. You need to conduct trials which prove the efficacy and safety of these products as you would with any other medication." Though what the AMA (and FDA) regard as sufficient trials are in fact so onerous as to be destructive of progress, a regulatory burden that blocks useful innovations and dramatically raises the cost of others. When listening to organizations like the AMA, keep in mind that they operate as a guild - their goal is to maintain high barriers to entry to their professional space so as to keep prices high. Regardless of the politics here, a weight of evidence for hormone therapies just doesn't exist, however. Despite the loud "anti-aging" marketplace, these therapies remain proven useful only for a small range of rather unpleasant diseases.

Debating the Oxidative Stress Model of Aging (June 22 2009)
You'll find plenty of healthy debate in the aging research community: "Currently, the Oxidative Stress (or Free Radical) Theory of Aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited ... Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice." Or that the antioxidant processes examined aren't particularly important to longevity. The best counterpoint to the paper's thesis I know of is the demonstrated use of mitochondrially targeted antioxidants to extend life span in mice.



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