22 Heat Shock Protein Gene Expression in Response to Physiologic Stress and Aging

Abstract

I. INTRODUCTION Human aging is accompanied by a progressive decline in physiologic processes and in particular by a decreased ability to maintain homeostasis when faced with the stresses of life (Shock 1961; Shock et al. 1984). Current concepts suggest that aging results at least in part from damage to molecules, cells, and tissues by a variety of toxic factors that either are endogenously produced or occur as a result of environmental exposure (Martin et al. 1993). Genetic systems have evolved to detect specific forms of damage and to activate the expression of genes whose products are presumed to increase the resistance of cells to such damage and/or to aid in its repair. Believing that the continued effectiveness of these genetic responses to stress may be a major factor in resistance to disease and aging, we initiated a series of studies to examine the expression of various stress response genes as a function of aging. Because the expression of heat shock proteins is the most highly conserved and best understood of these genetic stress responses, and because the beneficial effects of heat shock proteins during stress have been clearly documented, we have focused efforts on this group of proteins. Most of our knowledge concerning the homeostatic role of heat shock proteins has come from studies using cultured cells. Although much less is known about their expression in vivo, heat shock proteins are induced acutely in the intact animal in response to localized tissue injury, as well as systemically following heat stress...