New Paper Continues Confirmation of Age-Defying Diet

In the last 15 years a number of research groups around the world have converged on an explanation for how dietary restrictions can lead to lifespan extension. These teams have narrowed the search to a handful of compounds.*  The central candidate, by far, is an essential amino acid called methionine, found in high amounts in meat and fish, but in very low amounts in most plant foods.

Reducing consumption of this single amino acid extends lifespan by 15-44% in every laboratory animal tested to date. This effect is sufficient to completely explain previous results that found dietary restriction of total calories led to lifespan extension. Turns out it wasn't the calories -- it was the methionine.

Methionine restriction reduces visceral fat with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Methionine restriction also prevents age-associated increases in serum lipids.(source)

A new paper published this month by Koziel et al confirms previous methionine restriction results in human cell culture, mice, rats, fruit flies, and yeast. Koziel et al used human cell culture to specifically examine mitochondrial function and showed that oxidative stress is reduced by this dietary intervention.  This work supports the traditional free radical theory of aging-by-oxidative stress.

Methionine is an interesting amino acid because it promotes growth, including muscle and bone development. It is essential, and that is the point: restriction appears to promote a healthy stress-response that can confer adaptive resilience to senescence.  Other researchers have postulated that methionine restriction causes an increase in autophagy, the process whereby cells break down and recycle unused or damaged cell components. Instead of the free radical theory of aging, this theory would postulate that Methionine restriction induces a starvation-type response where cells begin to recycle their constituents at an increased pace. In this theory, "stress" is a good state to be in, because it puts cells in an active phase of self-repair. Cite: 1 and 2.

* The two other most promising age-defying compounds are rapamyacin (an antibiotic with a plethora of strange and powerful effects throughout the body) and resveratrol.  

"Biodemography of human ageing"

This article in the March 25th 2010 issue of Nature magazine confounds the rest of that issue's Insight Review of human ageing. For someone not versed in the field of demographic statistics used in this article, the graphs and conclusions are unique. By examining a kind of running average of life expectancy, the author is able to talk about the continuing increase in life expectancy.

"Humans will continue to suffer senescence -- but the process is not intractable. Mortality has been postponed considerably as a result not of revolutionary advances in slowing the process of ageing but of ongoing progress in improving health. If progress in reducing mortality continues at the same pace....then in countries with high life expectancies most children born since the year 2000 will celebrate their 100th birthday -- in the twenty-second century. "

Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila

This paper in Nature, December 31, 2009 disproves the theory of resource allocation in which "high survival, associated with dietary restrictino, and high reproductive rate, associated with full feeding, are mutally exclusive." The authors show that different combinations of amino acids are responsible for longevity and fecundity, and that both can occur when either methionine is the only amino acid in the diet or when methionine is excluded from an otherwise normal diet. Therefore, the standard tradeoff observed between allocating resources to repair or growth is based on a nutritional sensing and signalling pathway that must involve methionine.

The authors go on to show that this pathway is the insulin sugar-sensing pathway by knocking out insulin receptors in Drosophila. In the figure above flies expressing a dominant negative called lnRDN (diamonds) live much longer, regardless of diet, than do wildtype (triangles) and control with a deGAL4 promoter (squares). Whether these findings apply to humans could possibly be answered with population nutritional and health data, but these can be hard to access.

Very well written.