The diet known as calorie restriction (CR) is the most reproducible way to extend the
lifespan of mammals. Many of the early hypotheses to explain this effect were based on it
being a passive alteration in metabolism. Yet, recent data from yeast, worms, flies, and
mammals support the idea that CR is not simply a passive effect but an active, highly
conserved stress response that evolved early in life's history to increase an organism's
chance of surviving adversity. This perspective updates the evidence for and against the …