Fast track to longevity

Researchers have moved a step forward in understanding how calorie restriction is linked to lifespan extension in mammals.

Mar 28, 2005
Graciela Flores

Researchers have moved a step forward in understanding how calorie restriction is linked to lifespan extension in mammals. Johns Hopkins University cell biologist Pere Puigserver and colleagues report that SIRT1 – one of the mammalian homologs of Sir2, known to extend lifespan in yeast and worms – controls glucose metabolism in mice in response to fasting.1

Puigserver's group found that fasting signals induce the SIRT1 protein in the liver. "During starvation, there is an increase in pyruvate, a nutrient signal that induces translation of SIRT1, and an increase in NAD+, which functions as a substrate and as an activator of SIRT1," explains Puigserver. "The active SIRT1 interacts with PGC-1α, deacetylates it, and keeps it active, promoting glucose production in the liver." These results show that besides the hormonal control of PGC-1α through glucocorticoids and glucagon during fasting, there is a nutrient control as well, which targets SIRT1.

Brown University's Marc Tatar found the role of SIRT1 in nutrient sensing impressive. "There are hormonal inputs for sensing nutrients that are released systemically and circulate throughout the body," he says. "But what we are beginning to see is that there are also systems in which every cell can sense the nutrient condition in their own neighborhood and adjust their metabolism to their local nutrient conditions."