Sir2 Genes May Extend Lifespan

Although the legendary Fountain of Youth that brought Ponce de Leon to Florida in the sixteenth century is probably a myth, four researchers at Harvard Medical School (HMS) may recently have discovered the next best thing.

The researchers, led by HMS Associate Professor of Pathology David A. Sinclair, published a paper last month in the journal Science that detailed a finding they believe sheds new light on the role of genes in regulating aging.

The finding centers on a group of genes known as the Sir2 family. According to Sinclair, research over the last several years suggests the Sir2 gene plays an important role in regulating aging.

“It extends the lifespan of every organism it has been put into,” he said of the gene, adding that these organisms include yeast, worms, and fruit flies. Tests on mice are currently ongoing.

Sinclair said that the role of Sir2 is thought to be related to a well-known phenomenon in rats whereby restricting the animals’ caloric intake can increase their lifespan.

“Restricting how many calories a rat eats greatly protects it from diseases like cancer, heart disease, and even the aging process itself,” he said. “Sir2 is...mediating this process.”

But the new finding by the HMS researchers—who included Dudley Lamming, Oliver Medvedik, and Magda Latorre-Esteves, in addition to Sinclair—reveals that Sir2 does not serve this function alone. Rather, a group of related genes—the Sir2 family—plays a major role in regulating lifespan. Sinclair said that one of the genes in the family appears to control functions such as fat metabolism and cell survival, while another controls body temperature and the efficiency with which an organism uses energy, and yet others protect against diabetes.

“There’s not just one key regulator...each one plays a critical and distinct role,” he said.

Sinclair said that he and his fellow researchers are in the process of establishing the individual purpose of each gene in order to determine which ones can be used for medicines. They are currently using one of the genes in the Sir2 family to protect mice from brain disorders analogous to Alzheimer’s disease, dementia, and Huntington’s Disease, he said.

The discovery of the Sir2 family came about after researchers realized that even organisms that did not contain the original Sir2 gene could have their lifespans extended by calorie restrictions, Sinclair explained. “These other genes take over,” he said.

According to Sinclair, the Sir2 genes are effective in extending lifespan because they control the body’s own defenses against disease—defenses which, he argued, modern medicine has not utilized to their full potentials.

Sinclair said the power of the Sir2 family of genes could someday be harnessed to “stimulate the body to work harder and protect itself,” leading to a “whole new class of medicine that can treat many of the world’s diseases” including cancer, diabetes, Alzheimer’s, and even aging itself.

—Staff writer Matthew S. Lebowitz can be reached at mslebow@fas.harvard.edu.