On Leucine, Metabolism and Aging

Researchers continue to pull new knowledge from their ongoing investigations into metabolism and diet; matters are moving faster now that calorie restriction mimetic science is drawing much more funding into this field.

Leucine Deficiency Emulates Calorie Restriction

Organisms adapt metabolically to episodes of malnutrition and starvation by shutting down the synthesis of new proteins and fats and by using stores of these nutrients from muscle, fat, and the liver in order to continue vital functions. Cavener and Guo found that the removal of a single amino acid, leucine, from the diet is sufficient to provoke a starvation response that affects fat metabolism. "These findings are important for treating two major problems in the world," Cavener says. "The starvation response we discovered can repress fat synthesis and induce the body to consume virtually all of its stored fat within a few weeks of leucine deprivation. Because this response causes a striking loss of fatty tissue, we may be able to formulate a powerful new treatment for obesity."

"Emulates calorie restriction" is somewhat unwarranted, I think - it would be more accurate to say that this emulates some aspects of dietary restriction in general as applied to fat metabolism. It is interesting to see that, as scientists continue to deconstruct the workings of metabolism, ever more parts of the metabolic control system are found to be keyed to surprisingly specific components of diet.

Another item on leucine: it seems that we become less able to utilize this amino acid as we age, which leads to sarcopenia, or progressive age-related muscle loss. There is a modest weight of evidence for enhancing leucine intake with age on those grounds.

Muscle in adults is constantly being built and broken down. As young adults we keep the two processes in balance, but when we age breakdown starts to win. However, adding the amino acid leucine to the diet of old individuals can set things straight again. ... After the age of 40, humans start loosing muscle at around 0.5-2% per year. ... The team of researchers believe that the age-related problem results from defective inhibition of ubiquitin-proteasome dependent proteoloysis, a complex degradative machinery that breaks down contractile muscle protein, and that leucine supplementation can fully restore correct function.

These two views (of many) of the role of leucine form a good illustration of the complexity of metabolism - it's all so interconnected that any attempt to manipulate it safely and usefully requires an enormous amount of knowledge, or acceptance of a lot of risk. This insight is one basis for the engineering approach to tackling age-related degeneration, or other progressive conditions. Don't try to manipulate metabolism to slow things down - it's a hard job with limited rewards. For the much the same amount of expenditure, you could instead learn to repair progressive changes (damage, in other words) caused by metabolism to cellular and biochemical structure. This would be a matter of understanding how to fix up the damage to the existing engine, rather than the far greater understanding needed to build a better engine.

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