Longevity Meme Newsletter, December 22 2008

December 22 2008

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.



- More Evidence For Methionine Restriction
- On Consuming AGEs
- Our Folding@Home Team Hits Rank 100
- Discussion
- Latest Healthy Life Extension Headlines


Researchers are building a very good case for the health benefits of calorie restriction to largely - but not completely - be triggered by the amount of the dietary amino acid methionine ingested. Experiments show that the same intake of calories, but with up to 40% less methionine, produces results that look a lot like calorie restriction in smaller mammals: extended longevity, greater resistance to age-related disease, and so forth.


"While methionine restriction accounts for much of calorie restriction, it doesn't account for all of it. There may be multiple parallel mechanisms operating, which in turn suggests that building calorie restriction mimetic drugs that capture anywhere near the entire effect of actual calorie restriction will be challenging. Meanwhile, while research groups are spending hundreds of millions to billions of dollars on research and development, you can obtain the whole benefit of calorie restriction for just about free. Just start eating less, sensibly, while ensuring that your intake of micronutrients remains optimal."


Food for thought: will it be more costly to develop calorie restriction mimetic drugs that manipulate the methionine-related mechanism, or to develop a varied range of foodstuffs for a low-methionine diet? The latter is no doubt much harder than it might at first appear, but I imagine we'll see some food companies jump into the fray as evidence for the health benefits and safety of methionine restriction continues to mount.


Your metabolism generates advanced glycation end-products (AGEs) as a result of its operations. Like many other undesirable forms of biochemical gunk, they lead to damage and dysfunction as they accumulate. Diet is also a sizable source of AGEs, coming from any food browned by the Maillard reaction, such as cooked meat. As antioxidant research demonstrates, however, that a chemical affects cells in a petri dish in a certain way doesn't mean that eating it will accomplish the same result. It is a long and winding path from your stomach to the interior of your tissues.

Thus there has been some debate over whether AGEs in your diet contribute to degenerative aging in the same way as AGEs manufactured in your body. The latest research seems to suggest that they do, however. Mice fed an increased amount of AGEs showed accelerated biochemical damage in their tissues, characteristic of that caused by AGEs manufactured in the body:


"These results suggest that AGE-rich [diets] increase AGE accumulation, bringing about early events associated with lifestyle-related diseases."

There has been some speculation that a small fraction of the benefits of calorie restriction are due to a drop in AGE consumption. This work provides some indirect support for that theory.


I'm pleased to report that the Longevity Meme Folding@Home team, bolstered by the Immortality Institute volunteers and quarterly prizes for folding, is now in the top 100 teams:


Congratulations are due to all who organized, put up prizes, contributed processing cycles, and otherwise helped to make this happen. You can learn more about the distributed computing effort of Folding@Home at the Stanford University website:



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!




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/

Exercise, the Immune System, and Cancer (December 19 2008)
As you might know, one of the roles of the immune system is to hunt down and destroy cancerous cells before they can grow into tumors. That the immune system becomes damaged and dysfunctional in later life is one of the many reasons why cancer risk increases with age. Here is a paper that shows that exercise boosts the capacity of immune cells to kill cancer - as though you needed another reason to regularly exercise, given its many benefits to healthy longevity. "Natural killer cells (NK) induce the death of tumor cells [by] cytotoxicity, whereas platelets reduce the capacity of NK to destroy tumor cells. Physical exercise affects both immune function and platelet activity because responses depend on type, intensity, and duration of exercise. This investigation explores how various exercise regimens influence platelet-impeded cytotoxicity of NK to [tumor cells] ... Thirty sedentary men performed on three occasions moderate exercise), severe exercise and severe exercise after warm-up exercise ... Severe exercise enhances the cytotoxicity of NK to [tumor cells] and simultaneously promotes the platelet-impeded apoptosis of [tumor cells] induced by NK. However, warm-up exercise reduces the resistance of platelet to NK-[tumor cell] interaction, increasing the efficiency [of] cytotoxicity by NK after severe exercise."

More on Adult Brain Plasticity (December 19 2008)
Researchers are getting closer to inducing the adult brain to reconfigure and repair itself in response to damage: "The [study] identified a set of proteins - calpain and cortactin, which regulate and control the sprouting of neurons - a mechanism known as neural plasticity. ... During development, growing neurons are relatively plastic and can sprout new connections, however their plasticity levels drop rapidly as they mature and become integrated into neuronal networks. ... as a consequence, the central nervous system is unable to reorganize itself in response to injury or disease. ... This discovery is exciting because we now know that neurons haven't lost their capacity to re-grow connections, but instead are under constant repression by the protein calpain. If we can target therapies that block this mechanism, then neurons should be able to sprout new connections, therefore stimulating the brain's ability to repair its wiring network. ... The next step is to find a way to enhance neural plasticity without interfering with the good connections that are already in place."

Cell Polarity and Aging (December 18 2008)
Another good find from Ouroboros, an outline of differential distribution of damage to daughter cells and the origins of aging: "Let's pretend you are a unicellular organism - what would be the best strategy to ensure the long-term multi-generational survival of your lineage? One approach is to distribute everything equally amongst your two offspring. ... A second approach is to give all the crap to one of the two new cells and keep the other one pristine. Lets call these two cells the crap cell and the pristine cell. What's the result of this second strategy? Using our crap metric from above, the first cell accumulates 10 units of garbage over its lifetime and then gives it all to one offspring, the crap cell, and none to the other offspring, the pristine cell. Those cells then grow and by the time they divide each second generation cells have made 10 units of additional crap each. The crap cell has 20 units the pristine cell 10. The two cells divide and dump all their garbage on one of their offsprings. One cell starts with 20 units of crap, one cell with 10 units and two cells are again crap free. The end result of this strategy? Part of your descendents will become more and more decrepit as they fill up with crap, while others remain pristine."

Ouroboros on AGEs and Senenscence (December 18 2008)
From Ouroboros: "Advanced glycation endproducts (AGEs) have been implicated in age-related disease and aging itself, convincingly enough that significant effort has gone into finding compounds that can 'break' or reverse them. Among many unresolved questions: Are specific proteins AGEylated, and if so, which proteins are being modified within cells? Unterluggauer et al. report that in [senescent cells], the chaperone Hsc70 is modified by AGE ... If a major chaperone is modified by AGEs, and the modification is deleterious to its function, this could dramatically decrease the efficiency of protein folding, which (given that chaperones are proteins too) could dramatically decrease the number of chaperones, which [leads to a] garbage catastrophe ... (Then again: senescent cells persist in culture for a long time, implying that they have some way to deal with the admittedly hypothetical protein-folding death spiral implied in the previous paragraph.)"

Evidence For Cancer Stem Cells (December 17 2008)
Evidence both for and against the cancer stem cell hypothesis is arriving rapidly these days. Scientists "have answered a central question in cancer biology: whether normal stem cells can give rise to tumors. Stem cells are immature cells that can renew themselves and give rise to mature differentiated cells that compose the range of body tissues. In recent years, researchers have developed evidence that cancers may arise from mutant forms of stem cells. Like a brand-name product instantly identifiable by its trademarked logo, normal and cancerous stem cells display on their surface characteristic proteins, including Prominin1 or CD133. A key question in cancer biology has been whether these so-called cancer stem cells arise from normal stem cells or more mature cancer cells that somehow reacquire the characteristics of stem cells. ... investigators show that Prominin1 marks normal intestinal stem cells and that these cells, when mutated, give rise to intestinal tumors. The finding could also aid in identifying the source of cancer stem cells in the lung, kidney, brain, pancreas and other tissues." If cancer stem cells are in fact the root of a majority of cancers, then targeted therapies presently in development will ensure that cancer becomes a lot rarer a decade from now.

Aging: Genetic Program Versus Stochastic Damage (December 17 2008)
Via EurekAlert!: "Aging yeast cells accumulate damage over time, but they do so by following a pattern laid down earlier in their life by diet as well as the genes that control metabolism and the dynamics of cell structures such as mitochondria, the power plants of cells. These research findings [support] the theories that old age is the final stage of a developmental program AND the result of a lifelong accumulation of unrepaired cellular and molecular damage. ... The scientists first identified a mechanism closely linking life span to the dynamics of such lipids as cholesterol, triglycerides and fatty acids ... These fatty acids are constantly synthesized in the endoplasmic reticulum (ER), the cell's protein manufacturing factory. ... Low-calorie diets, which have been shown to increase lifespan and delay age-related disorders in nonhuman primates and other organisms, altered the way fats were processed in the yeast cells. The researchers assessed calorie restriction along with a number of known mutations that extend yeast lifespan against a variety of age-related changes in fat metabolism and lipid transport. ... Through the yeast model, [researchers] identified five groups of novel anti-aging small molecules that significantly delayed aging."

An Update on Progress in Treating Progeria (December 16 2008)
We should be at least a little interested in the accelerated aging condition Progeria (or HGPS), for as this ScienceDaily article points out: "Recent research indicates that all people, not just children with HGPS, produce small amounts of [the truncated Lamin A protein called]progerin, and that this mutant protein may play roles in aging or longevity ... The discovery of the gene responsible for the disease five years ago led scientists to the experimental drug that is now being evaluated in 28 children ... The 2003 discovery of the HGPS gene, named lamin A (LMNA), laid the groundwork for the clinical trial. ... scientists found that the minute change in the LMNA gene's DNA sequence dramatically changed the way in which the sequence was spliced by the cell's protein-making machinery. The end result was the production of an abnormal lamin A protein that is missing a stretch of 50 amino acids near one of its ends. ... Years of basic research studies showed that the Lamin A protein production depends on the farnesyl group molecules' attaching themselves to the pre-lamin A protein. This attachment - and progerin production - can be blocked by a FTI drug."

Continued Cataloguing of Stem Cells (December 16 2008)
ScienceDaily provides a good example of the sort of work taking place in the stem cell field at the moment. Near future applications are as much about understanding how to correct problems in human tissue as about building replacement tissue: researchers "have discovered stem cells in the esophagus of mice that were able to grow into tissue-like structures and when placed into immune-deficient mice were able to form parts of an esophagus lining. ... The immediate implication is that we'll have a better understanding of the role of these stem cells in normal biology, as well as in regenerative and cancer biology ... Down the road, we will develop a panel of markers that will define these stem cells and use them in replacement therapy for diseases like gastroesophogeal reflux disease [GERD] and also to understand Barrett's esophagus, a precursor to esophageal adenocarcinoma and how to reverse that before it becomes cancer."

The Masses Who Don't Have To Die (December 15 2008)
From Overcoming Bias: "More likely than not, most folks who die today didn't have to die! Yes, I am skeptical of most medicine because on average it seems folks who get more medicine aren't healthier. But I'll heartily endorse one medical procedure: cryonics, i.e., freezing folks in liquid nitrogen when the rest of medicine gives up on them. Yes even with modern anti-freezes, freezing does lots of damage, perhaps more than whatever else was going to kill you. But bodies frozen that cold basically won't change for millennia. So if whole brain emulation is ever achieved, and if freezing doesn't destroy info needed for [constructing an emulation based on scanning brain structure], if we think more likely than not, future folks could make an [emulation] out of your frozen brain. Since most folks who die today have an intact brain until the rest of their body fails them, more likely than not most death victims today could live on as (one or more) future [emulations]. And if future folks learn to repair freezing damage plus whatever was killing victims, victims might live on as ordinary humans." Those of us more in favor of continuity theories of identity prefer the latter option, and cutting edge cryonics now uses vitrification rather than freezing, which causes far less damage. But the point still stands: we have the technology to prevent irreversible death in a majority of cases, yet it is scarely used at all.

Methuselah Foundation Newsletter (December 15 2008)
The latest Methuselah Foundation newsletter is available, including a progress report on Methuselah Foundation Undergraduate Research Initiative (MFURI), and an interesting overview of anti-cancer OncoSENS and telomere research: "Cancer is one of the leading causes of death and thus one of the key targets of SENS. Our approach aims to tackle cancer by making it impossible for tumor cells to become immortal, rendering them harmless. Telomeres, the ends of chromosomes, play a key role in this process; specifically, we want to prevent them from being lengthened - a precondition of cellular immortality. In humans two mechanisms of telomere lengthening exist, of which the telomerase enzyme is the most well known; in my work, I focus on the less understood form called 'alternative lengthening of telomeres' (ALT). ... In the near future, I see OncoSENS taking two main directions; understanding ALT and - at first independently, but later in conjunction with that - providing a proof-of-principle in mice that telomerase-deficient stem cells can be successfully transplanted and largely prevent the emergence of malignant tumors."



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