Stimulus funds advance longevity research

- By Bruce Goldman

Jonathan RabinovitzEric Greer in Anne Brunet's lab

Stimulus funds allowed Eric Greer to continue his study of dietary restriction’s effects on a specific aspect of cell behavior in C. elegans. He is doing the work in the lab of Anne Brunet.

The lab of Anne Brunet, PhD, assistant professor of genetics, is like a Noah’s ark for basic-science research. Mice, fish and the tiny and therefore well-understood worm, C. elegans, serve as model experimental systems for studying aging and longevity.

One feature making the little worm (it consists of only about 970 cells) ideal for longevity research is its short life span. “C. elegans lives only 15 days, so you can quickly get results and use them to shape the next experiment,” said Brunet. “A mouse lives three years.” That’s a long wait time for a graduate student hurrying to get that PhD ticket punched and move up to the next career rung as a postdoctoral researcher.

Brunet’s former graduate student Eric Greer, PhD, now a postdoc in her lab, uses C. elegans to examine the molecular mechanisms underlying the effects of dietary restriction on life span. Dietary restriction (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 tested so far, including primates. “But the big question is, how?” Brunet said.

To answer that question, Greer is 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. When he received his doctorate in October 2009, he had been planning to move east, having lined up a postdoc position at Harvard Medical School. While he’s a native son of the Boston area, there was a downside to taking the new job: It meant that he would have to drop the longevity research project, which was a continuation of the work he had been doing at Stanford for several years.

“It was very important that he be able to complete this study,” Brunet said.

It wasn’t initially clear, though, where Greer would get the funding to do this work. The National Science Foundation grant that had covered his salary and stipend while he was a graduate student had skidded to a halt when he got his PhD. Fortunately, a National Institutes of Health stimulus grant providing $50,000 annually for two years has allowed Brunet to retain Greer as a postdoctoral researcher, so that his project can continue to completion.

All cells carry essentially the same genes in their nuclei. “But the genes that have to be accessible in your heart are very different from those that have to be accessible in, say, your foot,” Greer said. Gene-expression patterns likewise change as we pile up birthdays, undoubtedly contributing to the physical processes of aging. So where does diet fit into this picture?

A key factor in which genes are turned on and which turned off is DNA’s close association with specialized packing proteins called histones. “If you were to unravel the DNA in a single cell, it would be as tall as a person,” said Greer. “But it has to fit into a single cell, so it’s highly compacted by 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, he said. The difference appears to be mediated, in large part, by little chemical marks placed on histones by still other proteins. “It appears that these marks help determine which genes are accessible in the heart versus the foot,” Greer said. “We want to see how dietary restriction affects their placement.”

Since cutting caloric intake by 30 percent in this modern world of advertisements, supermarkets and fast food requires almost superhuman willpower, it would be nice to imagine that scientists will unravel less-challenging ways to slow the aging process: for example, a pill that reverses the gene-expression changes wrought by the passing years.

“Our goal is to understand the basic principles by which dietary restriction extends life span,” said Brunet. Still, that doesn’t mean that basic science advances won’t have very real implications. “People who are interested in translational research may someday use this information to try and find drugs that would mimic dietary restriction’s beneficial effect,” she added.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit

2023 ISSUE 1

How social factors make or break us