When cells get stressed: an integrative view of cellular senescence

TLDR

Senescence is a permanent cell‑cycle arrest marked by functional and morphological changes, typically triggered by prolonged proliferation or physiological stress, and has been largely studied as a telomere‑driven barrier to unlimited cell division, though its in vivo role remains poorly understood. The authors aim to reframe cellular senescence as a general stress‑response program rather than merely a telomere‑driven barrier to unlimited cell division. They examine how telomere shortening and uncapping contribute to senescence induction and argue for a broader stress‑response perspective.

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.