A review of why and how we age: a defense of multifactorial aging

Part 1: Longevity is optimized such that reproduction is maximized. Williams (Evolution, 11 (1957) 398-411) proposed pleiotropic genes with beneficial effects during youth and harmful effects at older ages. Because of environmental death (e.g. predation, disease, accidents), even a small increase in younger reproduction could outweigh a large harmful effect at older ages. Guthrie (Perspect. Biol. Med., 12 (1969) 313-324) and Kirkwood (Nature, 270 (1977) 301-304; New Sci., 81 (1979) 1040-1042; Physiological Ecology: An Evolutionary Approach, Blackwell, Oxford, 1981, pp. 165-189; Hum. Genet., 60 (1982) 101-121; Proc. R. Soc. Lond., B205 (1979) 531-546; Handbook of the Biology of Aging, 2nd Edn., Von Nostrand Reinhold New York, 1985, pp. 27-44) proposed that additional longevity requires a further investment of resources when young, thereby reducing the resources available for reproduction when young. The gene(s) controlling this partitioning of resources between younger and older reproduction are a good example of Williams's pleiotropic genes. Population biology provides a great deal of evidence of a tradeoff between younger and older reproduction. A "marginal longevity theorem" is proposed which states that for a population in equilibrium with its environment a marginal change in any gene affecting longevity should cause equal and opposite marginal changes in younger and older expected reproduction. Senescence is not irrelevant in the wild; rather, the amount of senescence in the wild results from a balance between its marginal costs to older reproduction and its associated marginal benefits in younger reproduction. Part 2: The wide variety of damage prevention processes in the body are subject to the problem of diminishing returns. Consequently, a broad spectrum of damage occurs in the body, varying in frequency, harmfulness, and ease of repair. The types of damage which are prevented or repaired tend to be more frequent, harmful, and easily prevented or repaired. In contrast, aging damage (which accumulates) consists of a large number of different types of damage which (when considered separately) are relatively infrequent, less harmful, and/or more difficult to repair. Only when these types of damage accumulate to become very numerous do they (when considered collectively) become significant. Since the selective advantages associated with senescence apply to all parts of the body, primary aging damage occurs in all tissues, cells, and subcellular organelles. The distribution of metabolic resources among the various damage repair and prevention processes is optimized.(ABSTRACT TRUNCATED AT 400 WORDS)