Inserm.fr – A new laboratory study of the anti-aging effects of calorie restriction reveals that a likely mechanism by which calorie restriction extends lifespan is boosting the level of pyruvate in cells. The pyruvate then causes a repeated or chronic low-level oxidative stress in the body that induces a cellular response (akin to exercise stress) that makes them “tougher” or more resilient.

Longevity studies have shown that 70 percent of the factors which influence an individual’s life expectancy relate to its environment and its lifestyle. This is the case for dietary restriction of calories, which involves reducing the amount of nutrition without under-nutrition. Moreover, this diet could help prevent the development of cancers. Hence, mechanisms may exist which are common to the control of longevity and development of tumors.

For several years, Marc Billaud, Florence Solari and their co-workers have studied the mechanisms involved in modulation of longevity and their links with cancer. In their research, they employ the model organism Caenorhabditis elegans. In the past, studying this small worm has led to pioneering discoveries in the description of the signalling pathways involved in longevity – pathways that have also been shown to be present in mammals.

In this study, the researchers isolated new “gerontogenes” (2) in C. elegans. Among these was the gene slcf-1, the inhibition of which produces beneficial effects on longevity, effects which are similar to those observed when food intake is restricted. They have shown that the restriction of food intake in C. elegans inhibits expression of the transport protein SLCF-1 in the intestinal cells and initiates an increase in the level of pyruvate. This alters the mitochondrial metabolism and induces an oxidizing stress.

This low intensity oxidative stress induces an adaptive response that is responsible for the increase in lifespan.

The same effects are found when the gene slcf-1 is inactivated (no production of transport protein SLCF-1) even if the food intake is not restricted.

This work has shown the importance of pyruvate metabolism in the control of lifespan under conditions of calorie restriction. Furthermore, it has also demonstrated that a protein known to have suppressing effects on tumors (the PTEN protein) is also involved in the cascade of events described above.

“It should be possible to perform tests on animal models, particularly mammals, to discover whether the simple addition of pyruvate to food mimics caloric restriction, exhibiting beneficial effects on the state of health and reducing the incidence of cancers”, explain the authors.

The abstract of the study is available free online here:

Pyruvate, calorie restriction, oxidative stress, and lifespan extension

Reference: Laurent Mouchiroud, et al. Pyruvate imbalance mediates metabolic reprogramming and mimics lifespan extension by dietary restriction in Caenorhabditis elegans. Aging Cell. Volume 10, Issue 1, pages 39–54, February 2011. [Published online November 15, 2010]. DOI: 10.1111/j.1474-9726.2010.00640.x