Life in healthy individuals begins with a period of rapid growth and development followed by a prolonged period of maturity that slowly and progressively declines into senescence. For treatment of specific diseases, physicians strive to prescribe drugs appropriate for a patient's age and health on the premise that they will bring about favorable, reproducible responses. But young children and elderly persons differ in many ways from mature adults in their middle years, including their capacity to handle and respond to intrinsic and extrinsic stimuli. Aging dominates both the structure and function of cells and organs over a much lengthier period of life than processes involved in growing and development, but knowledge of the mechanisms associated with aging is still very limited and generally less well understood than those that regulate growth and functional advancement.
Nathan Shock, a pioneer of the physiology of aging, observed early that not all physiological functions change with age (e.g., blood volume, blood glucose, acid-base balance), but that many organ systems exhibit extremely wide age-related individual functional differences. He provided evidence that some age-related changes in physiological functions can be ascribed to loss of cells or functional tissue, while certain other cellular functions truly do change with age (e.g., renal plasma flow, tubular secretion, cardiac output, peripheral arterial resistance).1 But representative biomarkers of aging that would allow a generalized definition of physiological age in humans have been difficult to identify, and no unifying explanation of the biology of aging that is applicable to cells and organ systems as well as to intact individuals has been proposed.
Technological advances that were introduced during the 1960s and 1970s have led to a better definition of ontogenic changes in organ and enzyme functions at the extremes of life. ''Developmental pharmacology,'' the part of pediatric pharmacology that deals with age-related differences in drug response in neonates and children, underwent appreciable modification and amplification during that pe-riod.2-5 At the same time, increases in elderly populations within developed countries directed attention to the biology of aging and stimulated interest in drug sensitivity in the elderly and the clinical aspects of therapeutic drug handling where ignorance was so marked.6-11 Recently, a number of modern, noninvasive techniques have provided new approaches to investigate morphological and functional changes in the elderly.
If adult values in the middle years of life are taken as standards of reference, physiological variations at life's extremes, especially during infancy and childhood, are much greater than during the middle years, and provision of safe and effective pharmacotherapy must take account of the magnitude and timing of such variations in addition to genetic variation. This chapter attempts to describe the sources and most consistent patterns of constitutional variations observed in development and aging.
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