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Is (Your Cellular Response to) Stress Killing You?

Biology of Aging, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.

Address correspondence to Felipe Sierra, PhD, Biology of Aging, National Institute on Aging, National Institutes of Health, 7201 Wisconsin Ave., Suite 2C231, Bethesda, MD 20892. E-mail: sierraf{at}nia.nih.gov

Abstract

Free radicals provide a generally accepted explanation for age-related decline in tissue function. However, the free radical hypothesis does not provide a mechanistic course of action to explain exactly how damage to macromolecules translates into the recognizable pathophysiology of aged organisms. Recent advances in the fields of DNA damage and cellular senescence point towards a substantial role for the DNA damage response, rather than DNA mutations per se, in the genesis of cellular and/or tissue damage. Furthermore, several studies suggest that protein damage can be at least as important as DNA damage in bringing about the aging phenotype. Here we propose that a "protein damage response," namely the ER/UPR (endoplasmic reticulum/unfolded protein) stress response is likely to play an important role in the aging process.

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