Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging.

From the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Box 165, Rockefeller University, 1230 York Ave., New York, NY 10021, where reprint requests should be addressed to Dr. McEwen. ©1998, Massachusetts Medical Society. VER 60 years ago, Selye 1 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 change 3 — is critical to survival. Through allostasis, the autonomic nervous system, the hypothalamic–pituitary–adrenal (HPA) axis, and the cardiovascular, metabolic, and immune systems protect the body by responding to internal and external stress. The price of this accommodation to stress can be allostatic load, 2 which is the wear and tear that results from chronic overactivity or underactivity of allostatic systems. O THE PHYSIOLOGIC RESPONSE TO STRESS