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This article briefly summarizes the Kent Award Lecture I gave at the annual meeting of The Gerontological Society of America held in Dallas, Texas, in November 2006. Cell death is a normal response of cells to cytotoxic damage due to both internal and external threats, and this cell loss is normally countered by proliferation of neighboring cells and/or replacement of these cells from progenitor cell pools. Maintaining tissue homeostasis is a critical challenge during aging, and this article describes a few aspects of the dynamic cell turnover that occurs continuously in vivo, with particular reference to the adverse effects of mutations that accelerate cell death through dysfunctional DNA metabolism, and how these events might contribute to aging in general. [ABSTRACT FROM AUTHOR]