Strong Link Between Sirtuin Proteins and Life Extension

Biology professor Leonard Guarente

Photo: Donna Coveney

By Ed Martinez

December 21, 2009

For decades, it has been known that cutting normal calorie consumption by 30 to 40 percent can boost lifespan and improve overall health in animals such as worms and mice.

A new study conducted by biologist Leonard Guarente from MIT showed that those effects are controlled by sirtuins—proteins that keep cells alive and healthy in the face of stress by coordinating a variety of hormonal networks, regulatory proteins and other genes.

Guarente notes that sirtuins bring about the effects of calorie restriction on a brain system known as the somatropic signaling axis, which controls growth and influences lifespan length. His research team genetically engineered mice whose ability to produce sirtuin (SIRT1) in the brain was greatly reduced. Those mice and normal mice were placed on a calorie-restricted diet. The normal mice showed much lower levels of circulating growth hormones, demonstrating that their somatropic signaling system was impaired—but calorie restriction had no effect on hormone levels of mice that could not produce SIRT1.

“This puts SIRT1 at a nexus connecting the effects of diet and the somatropic signaling axis,” said Guarente. “This is a major shot across the bow that says sirtuins really are involved in fundamental aspects of calorie restriction.”

Guarente and others believe that drugs that boost sirtuin production could help fight diseases of aging such as diabetes and Alzheimer’s, improving health in later life and potentially extending lifespan. Drugs that promote sirtuin production are now in clinical trials for diabetes patients, with results expected next year.