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8 Cellular Senescence: A Link between Tumor Suppression and Organismal Aging?

John M. Sedivy, Ursula M. Munoz-Najar, Jessie C. Jeyapalan, Judith Campisi


The aging of organisms occurs at virtually every level of complexity—from molecules to tissues to organ systems. Between these extremes are the basic units of life: individual cells. Among multicellular organisms, how do cells age? The deterioration of life processes in postmitotic cells—chronological aging—is explored elsewhere in this book. Here, we consider the aging of cells that retain the capacity for proliferation in adult organisms.

Normal somatic cells of higher metazoans, with the exception of germ cells and some stem cells, have a limited proliferative capacity (also referred to as replicative life span). This phenomenon was first formally described by Hayflick and Moorhead (1961), who observed that human fibroblasts, upon explant into cell culture, displayed an initial phase of rapid proliferation followed by a period of declining replicative potential. Eventually, all cells in the culture ceased dividing, but they remained in a viable and stable state. This postmitotic growth arrest was termed replicative senescence (Hayflick 1965) and, later, cellular aging.

The discovery of replicative senescence led to two important hypotheses. The first one proposed that cellular senescence recapitulates aspects of organismal aging and contributes to aging phenotypes in vivo (Hayflick 1985). Although there is mounting evidence to support this idea, it still rests largely on circumstantial evidence. The second hypothesis invoked cellular senescence as a mechanism that suppresses the development of cancer (Sager 1991). There is now substantial evidence to support this hypothesis (Campisi 2005; Hemann and Narita 2007). This chapter focuses on the links among cellular...

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