1985; Miller, 1990) must be understood if we are to understand the organism's aging phenotype. Dietary restriction as a modulator of lifespan in rats and mice represents an important probe for understanding aging changes (Masoro, 1988). Similarly, regulation of reproductive physiology and of the developmental process in general represents a potentially important analogue for the aging process and should be emphasized (Finch et al., 1985).

The fact that cells, tissues, and organs do not age at the same rate among species or even among individuals within a species poses a key complicating factor for these studies. Hepatocytes, for example, may be functionally youthful in an individual whose nervous system or cardiac function is seriously impaired as a result of aging or disease. The use of lifespan as an end point for aging has further hampered the interpretation of numerous studies. The field sorely needs measures of senescence based on functional capacity. Thus, descriptive studies of each system, evaluated in relation to overall functional competence and mortality risk, are critical to the development of meaningful biomarkers for aging, and for the identification of dysfunctional aging (senescence). Such biomarkers would increase scientific understanding of the factors that influence the rate of aging along the continuum of biological change and would contribute to the development of interventions that might delay or reverse dysfunctional aging (senescence). The concept of biomarkers applies at many levels, from cellular biology to the more complex interactions that are the object of scientific study in clinical, behavioral and social, and other areas of health care research (Sprott and Baker, 1988).

Abundant evidence is available of the accumulation of abnormal proteins during the course of aging and in the development of age-related diseases, such as the neurofibrillary tangles and beta-amyloid of Alzheimer's disease (Stadtman, 1988). Moreover, many tissues acquire inactive enzymes during aging (Dice and Goff, 1987). A major question concerns the pathogenesis of such abnormal proteins. The general question of altered gene expression in aging is of the utmost urgency if we are to understand the biological bases of aging, and the role of environmental influences, such as free radicals, radiation, and various toxicants, raises an additional and pressing set of questions about how the environment may influence aging (Ames et al., 1985).

While some research is focusing on various types of molecular damage, studies on the mechanisms of selective changes in gene activity should receive special emphasis. The powerful tools of recombinant DNA genetics are being applied to these questions. For

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