Moving closer to answer how caloric restriction extends life span

Eric Greer, a postdoc in the lab of Stanford scientist Anne Brunet, is using the tiny worm C. elegans to examine the molecular mechanisms underlying the effects of dietary restriction on life span.

Mark Davis, PhDDietary restriction, defined in this instance as consuming about 30 percent fewer calories than would be the case if food were freely available, is the most potent environmental intervention for extending life span in all organisms that have been tested so far, including primates. But the big question is how does it have this effect?

To answer that question, Greer has been concentrating on global changes that determine which of a cell’s genes are expressed (which in turn leads to the cell’s production of particular proteins) as animals age. Greer had earned his doctorate doing this longevity research, under the direction of Brunet, but he still had additional work he hoped to pursue. Unfortunately, the National Science Foundation grant that had covered his salary and stipend had skidded to a halt once he had received his PhD.

A National Institutes of Health stimulus grant providing $50,000 annually for two years has made it possible for Brunet to retain Greer as a postdoctoral scholar, so that his project can continue to completion.

The background for Greer's research is this: All cells carry essentially the same genes in their nuclei. But the genes that have to be accessible in your heart , for instance, are very different from those that have to be accessible in your foot. Gene-expression patterns likewise change as we pile up birthdays, undoubtedly contributing to the physical processes of aging. A key factor in which genes are turned on and which are turned off is DNA’s close association with specialized packing proteins called histones.This DNA-histone complex can be in a repressed state, all wound up so the cells gene-reading machinery can’t access a particular gene, or it can be in a more relaxed state corresponding to gene activation. The difference appears to be mediated, in large part, by little chemical marks placed on histones by still other proteins. These marks may help determine which genes are accessible in the heart versus the foot. Greer and Brunet are looking to see how dietary restriction affects their placement.

The research is intended to advance our basic scientific understanding of how dietary restriction extends lifespan. Still, it could have implications for how we can delay aging in the future. Most people can't reduce their caloric intake by 30 percent, and this research could lead to an alternative. It could be fodder for translational research to develop drugs that would mimic dietary restriction’s beneficial effect.