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Stress Response, Genotoxic Stress, Heat Shock Stress, Oxidative Stress, Theories Of Aging, Rate Of Aging

The concept of stress as a change in the environment that results in an internal response in living organisms can be traced to the nineteenth-century ideas of the physiologist Claude Bernard (1813–1878). Initially, the stress response involves important adaptive changes throughout an organism that are necessary to restore homeostasis, a term coined by Walter Cannon (1871–1945) to describe the internal bodily balance in physiological systems. Living organisms make adjustments within their cells to internal and external sources of stress in order to adapt, maintain function, and survive challenges to homeostasis. In contrast to the adaptive role of the stress response, Hans Selye (1907–1982) discovered that stress-related diseases were often the result of chronic effects of stress. Thus, the stress response is a double-edged sword with both beneficial and detrimental effects for the whole organism. Failure to mount an adequate stress response, or to terminate the stress response, or unrelenting stress results in additional threats to homeostasis over and above the stress that elicited the response in the first place. This is especially true during aging, when it becomes more difficult to maintain homeostasis due to accumulated damage and inadequate repair of molecules and cells. In his 1992 book on stress and aging, Robert Sapolsky pointed out that theorizing by gerontologists about stress focuses on both the decreased ability of older organisms to respond to stress and an increased incidence of stress-related diseases during aging.

Different stressful conditions produce a similar stress response, which Selye named the general adaptation syndrome. The ability of organisms to adapt to stress is regulated by the integration of the nervous, immune, and endocrine systems; is mediated by hormones; and is ultimately played out at the level of cells and molecules. Hence, stress has a prominent role in cellular aging. Cells have to withstand and respond to major types of stress in their environment, including genotoxic, heat shock, and oxidative stress. Old cells are more vulnerable than young cells to stresses in their environment. Lower organisms with short life spans serve as experimental models to study the effects of stress on cellular responses in relation to aging. In 2001, a Swedish group using fruit flies to screen for bacterially induced genes found a new humoral factor, Turandot A, that is released systemically in response to many types of stress and also at advanced ages. Overexpression of Turandot A helps adult fruit flies to survive heat stress without inducing heat shock or immune genes or its own synthesis, and therefore may act through a separate pathway or at a point where many types of stress converge. Cellular defense mechanisms important in aging include DNA repair, detoxification of chemicals, production of antioxidants and heat shock proteins, and even cell suicide as a result of initiating a cell death program. The effects of the major types of stress on cellular aging will be taken up in succeeding sections, following a general discussion of the stress response in relation to development of disease and altered function during aging.

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Medicine EncyclopediaAging Healthy - Part 4