Abstract
Over 60 years ago, Selye1 recognized the paradox that the physiologic systems activated by stress can not only protect and restore but also damage the body. What links these seemingly contradictory roles? How does stress influence the pathogenesis of disease, and what accounts for the variation in vulnerability to stress-related diseases among people with similar life experiences? How can stress-induced damage be quantified? These and many other questions still challenge investigators.This article reviews the long-term effect of the physiologic response to stress, which I refer to as allostatic load.2 Allostasis — the ability to achieve stability through change3 — . . .