Longevity Meme Newsletter, November 16 2009

November 16 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.



- Methuselah Foundation PSA Videos
- The Prospects for Engineering Better Memory
- Root Causes and Better Patches
- Discussion
- Latest Healthy Life Extension Headlines


The Methuselah Foundation volunteers have recently produced a series of public service announcement videos on the topic of aging and longevity science, now running on Hulu. They can also be found at YouTube, and a couple are embedded in this Fight Aging! post - see what you think:



Just as laboratories are bursting with exceptionally long-lived animals, their healthy lives extended via dozens of different mutations and therapies, you will also find that many different ways to enhance memory function are being explored. Here is one example:


"For my money, some of the most interesting results turning up these days involve the identification of single genes - and the proteins produced from their blueprint - that are crucial to the formation of memory. The expression of these genes might plausibly be adjusted to enhance memory, but the first item of business is to find them. ... A research team at Karolinska Institutet has now discovered that signalling via a receptor molecule called nogo receptor 1 (NgR1) in the nerve membrane plays a key part in this process. ... Medicines designed to target the NgR1 receptor system would be able to improve the brain's ability to form long-term memories."


Despite great strides in the field of human biology, most present day research and development is still aimed at patching over the symptoms of age-related decline. Much like patching over a dam without addressing the reasons why cracks form, this can do little more than delay the inevitable. Scientists who work on aspects of the Strategies for Engineered Negligible Senescence or other approaches aimed at the root causes rather than symptoms of aging are presently a minority.

But there is no sharp line to be drawn between "addresses root cause" and "patches symptoms." Proximate causes form chains in our biochemistry, one thing leading to another. A patch that addresses issues further down in the chain is probably better than a patch acting on the very end result. I am hopeful that as our knowledge of human biology continues to expand rapidly, the trend in applied research will be towards addressing root causes.

But let me point out an example, a potential therapy for age-related muscle loss based on replicating a rare but naturally occurring mutation in the myostatin gene:


"The researchers tried to use one protein called follistatin to impede the action of another, myostatin, that's known to inhibit muscle growth. They injected the gene for follistatin into the right legs of six healthy monkeys and after eight weeks, their right legs had grown and were larger than their left legs. 'We created a stronger muscle,' said Brian Kaspar, the principal investigator for Nationwide's research institute. 'We also showed that the muscle generated more force.'"

As it so happens, myostatin mutations may work because they boost the activity of satellite cells in muscle. Satellite cells are progenitor cells that build muscle when activated, and their activity declines with age. There is an ongoing debate as to whether this decline - and resulting loss of muscle mass and strength - is due to a reduction in the size of the satellite cell population, or whether the population is still large and capable of action, but other age-related changes in biochemistry block the activation of these progenitor cells. Or both. If the latter situation is largely the case, then manipulation of myostatin starts to look a little less like a patch, and a little more like aiming at root causes - boosting the activity of a cell population that is being recalcitrant. But this doesn't address the layer of causes below that; why age-related changes in our biochemistry cause stem cells to stop working in the first place:



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!




I see that David Kekich's Manhattan Beach Project meeting this month is getting some local press attention. He's an ambitious fellow, looking for ways to persuade enough money into the right projects to achieve SENS-like timelines for rejuvenation science: "David Kekich plans to end aging by the year 2029. Sound far-fetched? 'It know it sounds fictional,' the businessman said, 'but it's all based on hard, solid science. It will happen, it's just a matter of when.' He and more than a dozen scientists and researchers from the across the country will gather this weekend in Manhattan Beach for a three-day summit to design a plan for raising the necessary capital - 'only a few billion dollars,' he predicts - and the technology to lengthen human life spans within the next two decades. Dubbed the 'Manhattan Beach Project' after the secret atomic-bomb-building Manhattan Project of the 1940s, Kekich and his crew will 'collaborate on a battle plan to seek out and conquer anything that stands in the way of increased human life span,' according to press materials. ... human life span will continue to rise. ... For that reason alone, Kekich says this is a wise business investment - demand for services that extend life will be in huge demand, he predicts. ... We lose about 100,000 people to aging every day. We lose their talents, their relationships, their ability to solve problems. People are really at their peak in terms of talent at this age.'"

CAN MEMORY FILL UP? (November 13 2009)
That human memory can "fill up" has long been a staple of science fiction involving radical life extension. It seems like a reasonable projection - we only have so many brain cells - but that doesn't mean it happens in reality. For example, old memories might be consistently erased to make space. But here is an example of research in support of short term memory storage effectively becoming full due to changes that occur with age: "new neurons sprouted in the hippocampus cause the decay of short-term fear memories in that brain region, without an overall memory loss. ... the birth of new neurons promotes the gradual loss of memory traces from the hippocampus as those memories are transferred elsewhere in the brain for permanent storage. Although they examined this process only in the context of fear memory, [researchers say that] all memories that are initially stored in the hippocampus are influenced by this process. ... In effect, the new results suggest that failure of neurogenesis [such as happens with advancing age] will lead to problems because the brain's short-term memory is literally full. ... we may perhaps experience difficulties in acquiring new information because the storage capacity of the hippocampus is 'occupied by un-erased old memories.' ... voluntary exercise, which causes a rise in the birth of new neurons, sped up the decay rate of hippocampus-dependency of memory, without any memory loss."

From LiveScience: "The new study, which focused on Ashkenazi Jews, finds those who lived the longest had inherited a hyperactive version of an enzyme called telomerase that rebuilds telomeres. In effect, centenarians tend to have a top-notch body mechanic at work 24/7 repairing the hardware that runs the body, versus a normal person whose body's cellular control center is left to wear out with time. ... Humans of exceptional longevity are better able to maintain the length of their telomeres. And we found that they owe their longevity, at least in part, to advantageous variants of genes involved in telomere maintenance ... [Researchers] studied Ashkenazi Jews, a homogeneous population whose genetics are well-studied. Three groups were part of the research: A very old (average age 97) but healthy group of 86 people; 175 of their offspring; and a control group of 93 offspring of parents who lived a normal lifespan. ... Our research was meant to answer two questions. Do people who live long lives tend to have long telomeres? And if so, could variations in their genes that code for telomerase account for their long telomeres?... 'Yes' on both accounts, the scientists conclude."

THE TROUBLE WITH FLIES (November 12 2009)
Calorie restriction has such a strong effect on health and longevity in laboratory animals that any study failing to account for it - which is pretty much everything run prior to the mid 1990s - is potentially tainted. You think your treatment is providing benefits? No, it just makes the mice feel unwell, and so they eat less. Similarly, within the realm of deliberate calorie restriction studies, those that fail to correctly control feeding are probably producing incorrect results. No-one said that science was easy, and fly studies - where liquid foods are used - are particularly troublesome: "Recent studies have indicated that flies respond to dilute food solutions by compensatory feeding. The existence of compensation mechanisms calls for a reconsideration of the relationships between diet, feeding behaviour and longevity. This study shows that flies fed on liquid diets, sense sucrose and yeast nutrients and adapt to changes in the quantity and presentation of the two nutrients. ... Compensatory feeding suppresses the beneficial action of dietary restriction on longevity when flies are fed on liquid diets supplemented with yeast extracts. Flies which are given the choice to feed on separate yeast and sucrose food sources were longer lived than flies fed on nutrient mixtures. We conclude [that] food presentation is a major factor which determines the sensitivity of flies to dietary restriction."

While the general consensus in biogerontology circles appears to be that nuclear DNA damage contributes to degenerative aging, this is far from a settled claim. Here is a correlation that should add fuel to the fire: "The identification of the cellular mechanisms responsible for the wide differences in species lifespan remains one of the major unsolved problems of the biology of aging. We measured the capacity of nuclear protein to recognize DNA double strand breaks (DSB) and telomere length of skin fibroblasts derived from mammalian species that exhibit wide differences in longevity. Our results indicate DNA DSB recognition increases exponentially with longevity. Further, an analysis of the level of Ku80 protein [involved in DSB repair] in human, cow, and mouse suggests that Ku levels vary dramatically between species and these levels are strongly correlated with longevity. In contrast mean telomere length appears to decrease with increasing longevity of the species, although not significantly. These findings suggest that an enhanced ability to bind to DNA-ends [such as via the action of Ku80] may be important for longevity." In other words a better ability to repair double strand breaks in DNA correlates with species longevity. If you head over to the Fight Aging! archives for 2004 you'll find discussion of a theory of aging based on double strand breaks.

News from the cancer research community: "more than half of all human cancers have mutations that disable a protein called p53. As a critical anti-cancer watchdog, p53 masterminds several cancer-fighting operations within cells. When cells lose p53, tumors grow aggressively and often cannot be treated. ... [Researchers] have succeeded in shutting off the growth of tumors in which p53 is missing by turning up the production of TAp63 proteins, which make up one class of proteins produced by the p63 gene. TAp63 completely blocked tumor initiation, the team found, by inducing senescence, a state of growth arrest in which tumor cells are still metabolically alive but fail to divide. More importantly, turning up the levels of TAp63 in cells that did not have p53 blocked the progression of established tumors in mice. ... Tumor growth continued in the placebo group, with the tumors becoming five times larger within a week. In contrast, the tumors in the mice [producing TAp63] were abruptly shut down, and the tumors even shrank in size. Mills speculates that the tumor cells disappear because the newly senescent cells might attract the attention of the immune system, which have the ability to destroy them."

From ScienceDaily: "The search for the holy grail of regenerative medicine - the ability to 'grow back' a perfect body part when one is lost to injury or disease - has been under way for years, yet the steps involved in this seemingly magic process are still poorly understood. Now researchers [have] identified an essential cellular pathway in zebrafish that paves the way for limb regeneration by unlocking gene expression patterns last seen during embryonic development. They found that a process known as histone demethylation switches cells at the amputation site from an inactive to an active state, which turns on the genes required to build a copy of the lost limb. ... This is the first real molecular insight into what is happening during limb regeneration. Until now, how amputation is translated into gene activation has been like magic. Finally we have a handle on a process we can actually follow. ... This finding will help us to ask more specific questions about mammalian limb regeneration: Are the same genes involved when we amputate a mammalian limb? If not, what would happen if we turned them on? And if we can affect these methylation marks in an amputated limb, what effect would that have?"

PRIORITIES (November 10 2009)
If the end goal is to be able to grow replacement tissue for all parts of the body, sooner or later you will arrive at the engineering of male genitals. In fact sooner, it seems, which isn't much of a surprise given human nature. Via EurekAlert!: "In an advance that could one day enable surgeons to reconstruct and restore function to damaged or diseased penile tissue in humans, researchers have used tissue engineering techniques to completely replace penile erectile tissue in animals. ... After implantation with the replacement tissue, the rabbits had normal sexual function and produced offspring. ... Further studies are required, of course, but our results are encouraging ... Reconstructing damaged or diseased penile erectile tissue has traditionally been a challenge because of the tissue's unique structure and complex function. There is no replacement for this tissue that allows for normal sexual function. ... The scientists first harvested smooth muscle cells and endothelial cells, the same type of cells that line blood vessels, from the animals' erectile tissue. These cells were multiplied in the laboratory. Using a two-step process, the cells were injected into a three-dimensional scaffold that provided support while the cells developed. As early as one month after implanting the scaffold in the animal's penis, organized tissue with vessel structures began to form."

You'll recall that a few months ago the Immortality Institute community raised the funds needed for a proof of concept laser ablation of lipofuscin. The biochemicals making up lipofuscin build up in long-lived cell populations with age, degrading their ability to function. This is one of the root causes of age-related degeneration. The funded study aims to show that pulsed laser light can break down these unwanted chemical byproducts without damaging the cells that contain them. The end result of this research will hopefully be a demonstration that nematode worms treated in this way live longer, thanks to the removal of lipofuscin. The researcher, Nason Schooler, is blogging his progress, and updates also appear on the Immortality Institute page for the research project: "My leveling feet for the breadboards finally came in yesterday. I was waiting on them before doing my real optics setup, because I had to tear down all the optics in order to install them. Now the boards with feet are all set up and leveled, and I have the laser installed in a vise - which is a huge stability improvement over the wooden platform I had before. I'll try to get some pix up this weekend. As soon as the optics are setup, experiments will begin. I've got fresh batches of worms all ready to go."

CRYONICS IN THE UK (November 09 2009)
The Guardian looks at a non-profit cryonics initiative in the UK: "In a bungalow in Peacehaven, by the east Sussex seaside, a 72-year-old man and his 62-year-old wife are planning their future. There's no discussion of anything morbid, like death, because, as far as they are concerned there is no such thing as death. When they stop breathing, they will pass into a state of suspended animation. They will be frozen in a giant flask of liquid nitrogen at almost -200C, which will preserve their brains and organs in as fresh a state as possible until technology has advanced to the stage where they can be revived. ... I was aware from a very young age that life is very short. It occurred to me that no matter what you've got, you're still going to die. I remember thinking, 'I enjoy things: why does anybody want to die?' ... Alan now runs Cryonics UK, and every month he holds meetings with fellow cryonicists and potential converts to discuss the practicalities and potential problems of their suspension - of which there are many. First, upon so-called 'death', a team of experts must rush to their sides, pump out their blood and fill them with antifreeze. ... Second, there are no storage facilities in Britain, so patients will have to be transferred to the US or Russia. Third, science has some way to go before we can bring people back to life." This is much how the established cryonics organizations in the US started back in the day.



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