Lifespan: Why We Age—and Why We Don't Have To

by David A. Sinclair

What place does a diabetes medication have in a conversation about prolonging vitality? Perhaps it would have no place at all if not for the fact that, a few years ago, researchers noticed a curious phenomenon: people taking metformin were living notably healthier lives—independent, it seemed, of its effect on diabetes.16 In mice, even a very low dose of metformin has been shown by Rafael de Cabo’s lab at the National Institutes of Health to increase lifespan by nearly 6 percent, though some have argued that the effect is due mostly to weight loss.17 Either way, that amounts to the equivalent of five extra healthy years for humans, with an emphasis on healthy—the mice showed reduced LDL cholesterol levels and improved physical performance.18 As the years have gone by, the evidence has mounted. In twenty-six studies of rodents treated with metformin, twenty-five showed protection from cancer.19 Like rapamycin, metformin mimics aspects of calorie restriction. But instead of inhibiting TOR, it limits the metabolic reactions in mitochondria, slowing down the process by which our cellular powerhouses convert macronutrients into energy.20 The result is the activation of AMPK, an enzyme known for its ability to respond to low energy levels and restore the function of mitochondria. It also activates SIRT1, one of my lab’s favorite proteins. Among other beneficial effects, metformin inhibits cancer cell metabolism, increases mitochondrial activity, and removes misfolded proteins.21...