16 Determination of Aging Rate by Coordinated Resistance to Multiple Forms of Stress

This chapter explores the hypothesis that declines in aging rate, whether produced by evolutionary adaptations, single gene mutations, or dietary interventions, reflect alterations in a stress resistance pathway that increases cellular resistance to multiple forms of stress. We argue that such a stress resistance pathway evolved early in the eukaryotic lineage to allow small short-lived organisms to adjust their life history styles to intermittent environmental fluctuations and that as multicellular organisms evolved, they linked regulated stress-response mechanisms to a variety of hormonal and nutritional triggers specific for their own environmental niche. We believe that this model, although surely oversimplified, helps to explain much of the experimental data on stress and aging. We will try to show that the model provides a helpful heuristic framework for developing new experimental approaches to learn about the connections linking stress resistance, developmental biology, and endocrine controls to the aging process and, ultimately, to modulation of life span and most if not all of the diseases of aging. We must start with working definitions of two key terms: aging and stress. By “aging” we mean the process that gradually transforms healthy and vigorous adults into older adults with diminished ability to meet a wide range of physiological challenges and, concomitantly, increased susceptibility to multiple forms of illness, injury, and death. This definition emphasizes the process of aging, rather than its outcome, the aged individual, in order to highlight the changes that occur, even in young and middle-aged adults, and lead eventually to infirmity. In this...