Telomere Induced Senescence of Primary Cells

Richard Allsopp

Abstract Cellular senescence occurs when a cell enters a viable state of irreversible growth arrest. Since the first characterization of cell senescence for human cells, specifically human diploid fibroblasts, in classic experiments by Hayflick and Moorhead in the early 1960s (Hayflick and Moorhead 1961), primary cultures of human cells have been shown to undergo cell senescence in response to a number of different environmental stressors. For example, oxidative stress (von Zglinicki et al. 1995, Finkel and Holbrook 2000), exposure to irradiation (Finkel and Holbrook 2000), and inappropriate stimulation of mitogenic signaling pathways (Ridley et al 1988, Serrano et al. 1997), have all been shown to induce cell senescence in normal human cells grown in vitro. However, even when maintained in a stress-free environment under optimal growth conditions, cultures of normal diploid human cells still ultimately end up in a state of cell senescence after a finite number of population doublings. The cause of this phenomenon, specifically referred to as replicative senescence, or the Hayflick limit, after the discoverer Leonard Hayflick, eluded scientists until the mid-1990s, when researchers at Geron corporation (Bodnar et al. 1998) and the Whitehead Institute (Meyerson et al. 1998) discovered that the gradual erosion of telomeres, essential genetic elements that cap the ends of chromosomes, during proliferation of normal diploid human cells is what ultimately limits the replicative capacity of these cells and induces senescence. In this chapter, I will review the phenomenon of cell senescence, specifically, replicative senescence or telomere-induced senescence, the mechanism of telomere-induced senescence, and the role of replicative senescence in organismal aging.

Richard Allsopp

University of Hawaii, Institute for Biogenesis Research, John A Burns School of Medicine, Honolulu, Hawaii, United States. e-mail: [email protected]

K.L. Rudolph (ed.), Telomeres and Telomerase in Ageing, Disease, and Cancer. © 2008 Springer-Verlag Berlin Heidelberg

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