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Regulation of Cellular Senescence by the Retinoblastoma Pathway

  • Chapter
Aging of Cells in and Outside the Body

Part of the book series: Biology of Aging and its Modulation ((BIMO,volume 2))

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Abstract

The progressive decline in proliferative capacity is an intrinsic property of most normal somatic cells. Cells will lose division potential with roughly exponential kinetics and eventually reach a state of permanent growth arrest, referred to as replicative senescence [1]. Senescent cells remain viable and metabolically active, but cannot re-initiate DNA replication in response to physiological mitogenic stimuli [1–3]. Expression of senescence-associated (SA)-β-galactosidase in human skin cells has provided evidence that cells also undergo senescence in vivo [4]. One of the proposed consequences of the senescence response is organismal aging; skin biopsies from older individuals have a greater proportion of senescent cells in situ and a lesser proliferative capacity in culture [5, 6]. Also, cross-species comparisons suggest an inverse relationship between the proliferative lifespan of fibroblasts in culture and organism life span [7]. Certainly, decrements in cell renewal would compromise tissue function and integrity, but changes in the differentiated function of senescence cells would also contribute to aging. Senescent fibroblasts, for example, switch from matrix-producing to matrix-degrading cells, secreting large amounts of interstitial collagenase and stromelysin [reviewed in ref. 8] which may contribute to thinning of the dermis as observed in vivo. Thus, senescence may prevent the perpetual proliferation of cells during early adulthood, but the accumulation of dysfunctional, apoptotic-resistant senescent cells can have deleterious effects later in life and may promote the development of cancer [8].

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  1. Westmead Institute for Cancer Research at the Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, 2145, Australia

    Therese M. Becker & Helen Rizos

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Becker, T.M., Rizos, H. (2003). Regulation of Cellular Senescence by the Retinoblastoma Pathway. In: Kaul, S.C., Wadhwa, R. (eds) Aging of Cells in and Outside the Body. Biology of Aging and its Modulation, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0669-8_9

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