The Clinical Physiology of Aging

Abstract

Aging is a lifelong process, beginning at conception, ending at death, but largely genetically programmed and hence passed on to succeeding generations via gametocyte DNA. It is by definition a time-related process proceeding along a vector that is the resultant of genetic and behavioral/environmental forces, the former being defined as ‘primary aging’ and the latter as ‘secondary aging’. Thus descriptions of the physiology of aging in the ‘real world’ reflect individual or population gene-and-environmental interactions. A corollary principle holds that the earlier in the lifecourse that a process passes the clinical horizon from ‘normal’ to ‘abnormal’ (in the clinical context, from health to disease), the more likely it is that genetic forces will predominate (e.g., the rare, almost purely genetic homozygous autosomal recessive diseases of infancy and childhood); conversely, the later the clinical horizon is crossed and - especially germane to geriatrics - the later dysfunction, disability, and death will ensue, and the greater the role of behavioral/environmental determinants. Or, put otherwise, at one extreme of the lifecourse, childhood disorders are more likely to be attributable to single, genetic and notably simply-inherited or homozygous recessive disorders. At the other end of life, diseases of old age rarely if ever are caused by single-gene abnormalities; in fact, all disorders of old age are multifactorial in origin. In between these extremes, diseases that express themselves throughout adulthood but before old age reflect varying proportions of genetic and behavioral/environmental influences. Although much has recently been written of so-called ‘longevity genes‘, and whereas no doubt certain patterns of DNA confer particularly robust health and resistance to disease, such patterns are most likely to reflect the hybrid vigor of the ‘wild type’ (i.e., lack of mutant genes that increase vulnerability) and, in any event most probably are highly polygenic as well. Thus it appears to be more the absence of major disease-conferring genes than the presence of longevity genes per se that represents the genetic basis of long life. All this is by way of introducing the physiology of aging as a largely time-dependent, stochastic process, the efficiency of which generally increases rapidly during infancy and childhood (Fig. 1), reaches a maximum around age 30 (with much variance about that age among different systems and especially among different individuals), declines slowly and almost imperceptibly throughout mid-life (defined by the author as 25–75 years, age 50 being a convenient midpoint of midlife that also coincides with the average age of menopause in women), and decreases in accelerating fashion in old age, often ending in a terminal cascade of vulnerability, frailty, dysfunction, dependency, and death.