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9 Telomeres and Aging

Calvin B. Harley


More than 30 years ago, Hayflick first described the limited replicative capacity of normal human fibroblasts in culture as a manifestation of cellular senescence (for review, see Hayflick 1965; Goldstein 1990). In this process, the majority of cells in a population fail to divide in response to a variety of normal growth stimuli after a characteristic number of divisions, but they do not die. Instead, they remain metabolically active, but with an aberrant pattern of gene expression (see West et al. 1989). Numerous other somatic cell types, including epithelial cells, endothelial cells, myoblasts, astrocytes, and lymphocytes, have also shown evidence of a clock that limits their division capacity (Stanulis Praeger 1987; Harley 1988). This clock appears to utilize cell divisions as the unit of time rather than chronological or metabolic age (Dell’Orco et al. 1973; Goldstein and Singal 1974; Harley and Goldstein 1978) and hence has been called a “mitotic clock.” Although the maximum division capacity in culture of a human somatic cell population from a young, normal individual varies significantly from donor to donor and cell type to cell type, it typically falls in the range of 50–100. This limit decreases as a function of donor age, presumably reflecting the replicative history of the cells in vivo. Other vertebrate species, although less well studied, also demonstrate a limited proliferative capacity for somatic cells, and a positive correlation can be drawn between species longevity and cell life span (Goldstein 1974; Rohme 1981). These data, together with the plausible hypothesis...

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