Pacemaker Theories
Certain organs or organ systems (eg, the immune and neuroendocrine systems, notably the hypothalamus) are thought to be intrinsic pacemakers of the aging process, genetically programmed to involute at specific times during an organism’s life span. This programmed senescence is hypothesized to affect the aging of the entire organism.
With aging, both B- and T-cell functions decline, controlled largely by the major histocompatibility complex (MHC). T-cell functions are more impaired, the decline paralleling the involution of the thymus gland, which begins in adolescence. In studies of mice that are identical except for MHC, B- and T-cell functions closely correlate with life span. Also, the age-related increase in malignancies may be related to the age-dependent decline in cellular immune surveillance.
As another example, adrenergic activity increases with age and beta-mediated vasodilation decreases. These changes may be linked to age-related increases in blood pressure, impaired carbohydrate tolerance, and altered sleep patterns.
Studies of hypophysectomized animals receiving hormone replacement therapy suggested that aging was slowed and prompted a search for a death hormone, whose level increases with age, or a Methuselah hormone, whose level decreases with age. However, no data support these notions.
All of these theories fail to explain the origin of the changes in the pacemaker system itself. Also, they fail to take into account that not all organisms have well-developed immune or neuroendocrine systems.
Genetic Theories
Genetic factors are important determinants of aging, although most mechanisms involved are unknown. Life span is remarkably specific for each species, yet even within species genetic factors are important. In humans, the life expectancy of identical twins is more similar than that of siblings, and some families demonstrate a strong predisposition for longevity. Mutant varieties of Caenorhabditis elegans, a nematode, have been produced with life spans increased by 50%; the increase appears to result from a single gene in some strains. Researchers are now attempting to clone and examine this gerontogene.
Variability
Some biologic changes in the elderly are related to aging alone, while others result from disease. In evaluating and managing health and disease in the elderly, it is important, although not always possible, to understand and recognize the difference.
The rate of age-related decline in organ function varies greatly; thus, people become less alike as they age. Also, within any individual, the functions of different organs decline at different rates, so that kidney function may decline more quickly than heart or lung function.
Age-adjusted criteria have been established for several clinically important functions; eg, spirometric measures are commonly expressed as “percent of expected” for age and body size, and cardiac exercise tolerance tests use age-adjusted criteria for maximum heart rate. With aging, glomerular filtration rate (GFR) declines, and creatinine clearance falls about 10 mL/min for each decade. Because endogenous creatinine production also falls, however, normal serum creatinine levels remain unchanged. Thus, in the elderly, serum creatinine levels reflect a substantially lower GFR. Understanding these changes is important in prescribing drugs for the elderly. However, these are average changes for age, and the variability in function makes applying averages to each individual difficult.
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