Does functional depletion of stem cells drive aging?

The regenerative power of stem cells has raised issues about their relation to aging. We focus on the question of whether a decline in the function of stem cells may itself be a significant feature of aging. The question is implicitly two-fold: does functional depletion of stem cells affect the accumulation of aging-related deficits, and--whether or not depletion is significant--can activation of stem cells alleviate deficits? Two types of system are considered: 1) the exhaustible pool of ovarian follicles. The depletion of follicles leads to the aging-related phenomenon of menopause; and 2) the reserve of hematopoietic stem cells. Substantial numbers are sustained throughout life, but in mouse models, endogenous replicative activity has been shown to decline sharply with age. We discuss the possible implications of these observations for the rate of aging and the prospects for intervention.