Mental Health

You'll recall that experiments restricting intake of the dietary amino acid methionine - without restricting calories - demonstrate some of the same beneficial health effects as calorie restriction. This suggests that the level of methionine ingested is primarily what cues our biochemistry to produce the benefits it does under a low calorie diet that still supplies the right levels of micronutrients. See, for example:

• Methionine Restriction and Longevity
• The Metabolic Basis of Longevity
• On Methionine Restriction, Suppression of Mitochondrial Dysfunction and Aging

Now here's a reversal of these experiments, in which researchers restrict all the other dietary amino acids except methionine, and come to much the same conclusion:

Previous studies have shown that the decrease in mitochondrial reactive oxygen species (mitROS) generation and oxidative damage to mitochondrial DNA (mtDNA) that occurs during life extending dietary restriction also occurs during protein or methionine restriction, whereas it does not take place during carbohydrate or lipid restriction.

In order to study the possible effects of other amino acids, in this investigation all the dietary amino acids, except methionine, were restricted by 40% in male Wistar rats (RESTAAS group). After 6-7 weeks, experimental parameters were measured in the liver.

...

[The] results, together with previous ones, strongly suggest that the decrease in mitROS generation and oxidative damage to mtDNA that occurs during dietary restriction is due to restriction of a single amino acid: methionine. They also show for the first time that restriction of dietary amino acids different from methionine decreases mitochondrial protein oxidative modification [and] increases SIRT1, in rat liver.

Meaning that 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 an 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.

Regular readers will know that advanced glycation endproducts (AGEs) are not a good thing; they're one of the types of biochemical gunk that accumulate in our tissues to degrade function and cause follow-on issues relating to that lost functionality.

Problems caused - or not helped - by AGE buildup include kidney disease, and the many variations of blood pressure and heart conditions caused by a lack of elasticity in the tissues of heart and blood vessels. Diabetics in particular suffer due to more rapid accumulation of AGEs based on their metabolic biochemistry (e.g. high blood sugar, inflammation, free radicals).

You might also recall some of my posts on RAGE, the receptor for AGEs and how that fits in to the way in which AGEs damage the workings of your biochemistry.

At least some of the degenerations brought on by AGE buildup can be laid at the feet of the interaction with RAGE, and the resulting actions then taken by your cells. Cell receptors are like keyboards or buttons - hit them with the right sort of molecules and you're instructing the cell to take action.

There is, however, some debate over the role of AGEs ingested with food - cooked meat is comparatively high in AGEs, for example, and pretty much anything else that involves the Malliard reaction. Do these AGEs contribute to damage in the same way as those generated inside the body as a side effect of the operation of human metabolism? Here's a recent paper on the topic:

Effects of high-AGE beverage on RAGE and VEGF expressions in the liver and kidneys

BACKGROUND: The formation and accumulation of advanced glycation end products (AGEs) increase in some lifestyle-related diseases as well as in aging; however, little is known about the relationship between food-derived AGEs and the pathology of such diseases.

AIM OF THE STUDY AND METHODS: To explore whether food items containing high levels of AGEs are involved in the development of lifestyle-related diseases, rats were orally administered a commercial high-AGE beverage (LB-A) ... With a particular focus on angiogenesis-associated diseases, the gene expressions of vascular endothelial growth factor (VEGF) and the receptor for AGEs (RAGE) were examined in the liver and kidneys using real-time reverse transcription-polymerase chain reaction. Moreover, AGE deposition was immunohistochemically investigated in these tissues.

RESULTS AND CONCLUSIONS: Hepatic VEGF expression was significantly increased in rats administered LB-A ... Furthermore, immunohistochemical analysis detected glucose-derived AGE-positive cells in the liver from the LB-A group. These results suggest that AGE-rich beverages increase hepatic VEGF expression and AGE accumulation, bringing about early events associated with lifestyle-related diseases.

Fair evidence to suggest that reducing your AGE intake in addition to reducing your overall calorie intake might be a good idea over the long term.

I'm pleased to note that the volunteer folders-at-home who gather at the Immortality Institute forum have pushed the Longevity Meme Folding@Home team into the top 100 list - it's sitting right at rank 100 as I type this. I'd love to say I helped, but the steady climb through the ranks and increasing donation of computational resources is really all due to the hard work of those who organizated, encouraged, and recruited to grow the team to its present size. Well done all. There is a celebratory discussion thread underway over at the Immortality Institute.

Feel free to set off some fireworks or eat some cake or something to mark the occasion.

When the team hit rank 200 at the start of this year, I donated a small chunk of change to the Methuselah Foundation as an incentive for the folders. The team has sprinted ahead to rank 100 faster than I had anticipated given the competition - and so has caught me without a plan as to what to do to mark the occasion. Since you can't go far wrong by offering money, I think I'll donate a further $2000 to the Methuselah Foundation this year in support of Strategies for Engineered Negligible Senescence research.

Keep up the good work!

The mailing list of the Gerontology Research Group is something of a watering hole for many of the interesting folk in the pro-longevity gerontology community and related supporters of medical intervention to extend healthy life. Members include the Supercentenarian Research Foundation board, Methuselah Foundation volunteers, calorie restriction researchers, transhumanist writers, and so forth. L. Stephen Coles of the GRG recently penned a short editorial on the limits of longevity which closes with:

We should appreciate that the really-important parameters of longevity operate at the molecular level, such as the accumulation of sticky amyloid compounds which relentlessly infiltrate all our organs, the mechanism for which we have yet to decipher. When we do figure it out (science) and when we learn what to do about it (medicine), "all bets (on life-insurance-policy planning) will be off." We will be on the road to a real revolution in the human condition.

It being that time of year, I should note that the Supercentenarian Research Foundation is soliciting donations:

We seek to further scientific research into to why Supercentenarians live as long as they do? (And, conversely, why they don't live longer still?) We are incorporated and have held many meetings of our Board of Directors. We have received approval for our 501(c)(3) non profit, tax-exempt status from the US Internal Revenue Service. Nevertheless, we are urgently in need of "seed money" to fund the formation of an international team of physicians and investigators who could travel to visit each of our living Supercentenarians around the world in person before they are no longer with us. Obviously, the data that we plan to obtain is a precious resource that could disappear from our radar screens unless we get started soon.

Biotechnology and life science research is forging ahead despite the steadily worsening situation in bringing medical advances to market - stifling regulation that seems to do little but get worse year after year, and now an ongoing economic collapse that looks set to continue for some time. Here are a couple of examples from the field of regenerative medicine in the past few days:

Single Adult Stem Cell Can Self Renew, Repair Tissue Damage In Live Mammal

The transplanted adult stem cell and its differentiated descendants restored lost function to mice with hind limb muscle tissue damage. ... Unlike tumor cells, the transplanted stem cells achieved homeostasis, growing to a stable, constant level and ceasing replication. After demonstrating that the transplanted stem cells proliferated and fully restored the animal's lost function, Sacco and Blau recovered new stem cells from the transplant with full stem cell potency, meeting the final "gold standard" test for adult multipotent stem cells.

Single virus used to convert adult cells to embryonic stem cell-like cells

Researchers have greatly simplified the creation of so-called induced pluripotent stem (iPS) cells, cutting the number of viruses used in the reprogramming process from four to one. Scientists hope that these embryonic stem-cell-like cells could eventually be used to treat such ailments as Parkinson's disease and diabetes.

New Way To More Rapidly Generate Bone Tissue Developed

Using stem cell lines not typically combined, researchers [have] designed a new way to "grow" bone and other tissues.

...

The inability to foster angiogenesis - a physiological process involving the growth of new blood vessels from pre-existing vessels - has been a major roadblock in tissue regeneration. Previous approaches have included the use of angiogenic growth factors and the fabrication of artificial blood vessels. However, there are problems associated with these approaches. Among these problems: artificially fabricated blood vessels do not readily branch out and network with host blood vessels, and blood vessels induced by angiogenic growth factors tend to be immature and "leaky."

To overcome these obstacles, a team of Columbia researchers has co-transplanted hematopoietic and mesenchymal stem/progenitor cells to promote the regeneration of vascularized tissues. What they found was that the tissue regenerated in bone more rapidly than when either type of stem cell was used alone.

It is encouraging to have seen a steady stream of improvements to new techniques this past year. Researchers are moving rapidly to build a sound basis for the near-future construction of replacement organs and directed regrowth of damaged tissue inside the body.