Definition of Aging

Aging is not a single biological event but a process in which multiple biological events accumulate in different tissues over time. Despite the complexity of this process, a workable operational definition is that "aging is the time-independent series of cumulative, progressive, intrinsic, and deleterious (CPID) functional and structural changes that usually begin to manifest themselves at reproductive maturity and eventually culminate in death" (Arking, p. 12).

Although senescence often is used interchangably with aging, here it will be used to refer specifically to the changes that underlie the loss of biological function that are characteristic of aging. Studies at the cellular level have shown that the inability of cells to continue dividing in vitro is accompanied by substantial alterations in patterns of gene expression. These SAGE (i.e., senescence-associated gene expression) patterns are objective although complex indicators of a phenotype that differs from that of a normal (i.e., "young") cell primarily in its altered repertoire of expressed functions. It is the author's belief that the term senescence soon will gain a more precise meaning as these SAGE patterns are cataloged and those associated with a loss of function are identified. Tissue-specific manifestations of age-related disease, such as congestive heart failure, are being characterized in terms of their own particular SAGE patterns. Aging was defined above as being time-independent, for which there is strong theoretical support, but this has been demonstrated empirically in only a few instances (e.g., Finch). The existence of tissue-specific changes in SAGE patterns supports this concept by providing a mechanism by which functional loss can occur independently of time.

Aging thus should be viewed as being composed of a series of such patterns of gene expression, certain of which when induced by a variety of internal or external stimuli result in (or inhibit) a SAGE cascade, leading to the alteration of cellular and tissue functions. The large differences in life span between mice and humans, for example, can be ascribed in part to the greater efficiency of the cellular anticancer defenses in humans and thus their gene expression patterns, not to the circular observation that mouse cells live "faster" than do human cells. Also, the differences in life spans between individuals in one species, such as humans, can be ascribed to the genetic and contingent factors that collaborate to confer some extraordinary stability (in the case of centenarians) or instability (in the case of premature mortality) of their SAGE patterns. Time is, for a number of technical and conceptual reasons, a poor measure of age; and researchers will likely use SAGE patterns and other biomarkers of aging in the future. The candles on the physiologically correct (P.C.) birthday cakes of the future might be based on gene expression patterns.

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