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Review
. 2018 Apr 2;128(4):1238-1246.
doi: 10.1172/JCI95148. Epub 2018 Apr 2.

Mechanisms and functions of cellular senescence

Nicolás Herranz  1   2 , Jesús Gil  1   2
Affiliations
Review

Mechanisms and functions of cellular senescence

Nicolás Herranz et al. J Clin Invest. .

Abstract

Cellular senescence is a highly stable cell cycle arrest that is elicited in response to different stresses. By imposing a growth arrest, senescence limits the replication of old or damaged cells. Besides exiting the cell cycle, senescent cells undergo many other phenotypic alterations such as metabolic reprogramming, chromatin rearrangement, or autophagy modulation. In addition, senescent cells produce and secrete a complex combination of factors, collectively referred as the senescence-associated secretory phenotype, that mediate most of their non-cell-autonomous effects. Because senescent cells influence the outcome of a variety of physiological and pathological processes, including cancer and age-related diseases, pro-senescent and anti-senescent therapies are actively being explored. In this Review, we discuss the mechanisms regulating different aspects of the senescence phenotype and their functional implications. This knowledge is essential to improve the identification and characterization of senescent cells in vivo and will help to develop rational strategies to modulate the senescence program for therapeutic benefit.

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Conflict of interest statement

Conflict of interest: JG is a consultant to Unity Biotechnology, which also funds research in his laboratory. JG and NH are named inventors in filed patents related to senolytic therapies (GB1708458.3 and GB1708456.7 to JG and NH).

Figures

Figure 1
Figure 1. Phenotypic characteristics of senescent cells.
Diagram depicting some of the phenotypic alterations associated with senescence initiation, early senescence, and late phases of senescence.
Figure 2
Figure 2. Molecular pathways controlling growth arrest during senescence.
A variety of stressors induce senescence-associated growth arrest. Cell cycle exit is regulated by induction of the p16INK4a/Rb and p53/p21CIP1 pathways. Figure reproduced with permission from McHugh and Gil (126).
Figure 3
Figure 3. The SASP is an important mediator of the pathophysiological functions of senescent cells.
Scheme summarizing some of the functions associated with the SASP.
See this image and copyright information in PMC

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