When cells get stressed: an integrative view of cellular senescence
Ittai Ben-Porath, Robert A. Weinberg
Ittai Ben-Porath, Robert A. Weinberg
Published January 1, 2004
Citation Information: J Clin Invest. 2004;113(1):8-13. https://doi.org/10.1172/JCI20663.
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When cells get stressed: an integrative view of cellular senescence

Abstract

Cells entering a state of senescence undergo a permanent cell cycle arrest, accompanied by a set of functional and morphological changes. Senescence of cells occurs following an extended period of proliferation in culture or in response to various physiologic stresses, yet little is known about the role this phenomenon plays in vivo. The study of senescence has focused largely on its hypothesized role as a barrier to extended cell division, governed by a division-counting mechanism in the form of telomere length. Here, we discuss the biological functions of cellular senescence and suggest that it should be viewed in terms of its role as a general cellular stress response program, rather than strictly as a barrier to unlimited cycles of cell growth and division. We also discuss the relative roles played by telomere shortening and telomere uncapping in the induction of senescence.

Authors

Ittai Ben-Porath, Robert A. Weinberg

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Figure 2

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Telomere uncapping at senescence. The nucleoprotein structure at the end...
Telomere uncapping at senescence. The nucleoprotein structure at the end of telomeres presumably forms a protective cap. This structure may be composed of the T-loop (a), which is formed by the invasion of the single-stranded overhang into an upstream double-stranded region of the telomere, and of protective telomere-binding proteins such as TRF1, TRF2, and POT1. As cells approach replicative senescence, the double-stranded portion of the telomere shortens, and the single-stranded overhang is eroded (b). This may cause the collapse of the telomere cap and the exposure of the telomere end, which is detected by the DNA damage machinery and leads to the activation of the senescence program (c). Telomerase activity, apart from stabilizing overall telomere length, can prevent overhang erosion and protect the telomere cap, thereby circumventing senescence (d). TERT, telomerase enzyme reverse transcriprase.