A Genetic Flip-On Switch for Longevity

By Jane Farrell

Newly discovered genetic switches that increase lifespan and boost fitness in worms are also linked to increased lifespan in mammals, offering hope that drugs to flip these switches could improve human metabolic function and increase longevity.

These so-called epigenetic switches, discovered by scientists at the University of California, Berkeley, and the École Polytechnique Fédérale de Lausanne in Switzerland, are enzymes that are ramped up after mild stress during early development and continue to affect the expression of genes throughout the animal’s life.

When the researchers looked at strains of inbred mice that have radically different lifespans, those with the longest lifespans had significantly higher expression of these enzymes than did the short-lived mice.

“Two of the enzymes we discovered are highly, highly correlated with lifespan; it is the biggest genetic correlation that has ever been found for lifespan in mice, and they’re both naturally occurring variants,” said Andrew Dillin, a UC Berkeley professor of molecular and cell biology. “Based on what we see in worms, boosting these enzymes could reprogram your metabolism to create better health, with a possible side effect of altering lifespan.”

These are the first epigenetic modifiers known to affect metabolic function and longevity, though others are known to affect either metabolism or lifespan.

The discoveries will be reported in two papers to appear in the May 19 issue of the journal Cell.