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Biogerontology

, Volume 15, Issue 6, pp 627–642 | Cite as

Senescent cells: SASPected drivers of age-related pathologies

  • Yossi Ovadya
  • Valery Krizhanovsky
Review Article

Abstract

The progression of physiological ageing is driven by intracellular aberrations including telomere attrition, genomic instability, epigenetic alterations and loss of proteostasis. These in turn damage cells and compromise their functionality. Cellular senescence, a stable irreversible cell-cycle arrest, is elicited in damaged cells and prevents their propagation in the organism. Under normal conditions, senescent cells recruit the immune system which facilitates their removal from tissues. Nevertheless, during ageing, tissue-residing senescent cells tend to accumulate, and might negatively impact their microenvironment via profound secretory phenotype with pro-inflammatory characteristics, termed senescence-associated secretory phenotype (SASP). Indeed, senescent cells are mostly abundant at sites of age-related pathologies, including degenerative disorders and malignancies. Interestingly, studies on progeroid mice indicate that selective elimination of senescent cells can delay age-related deterioration. This suggests that chronic inflammation induced by senescent cells might be a main driver of these pathologies. Importantly, senescent cells accumulate as a result of deficient immune surveillance, and their removal is increased upon the use of immune stimulatory agents. Insights into mechanisms of senescence surveillance could be combined with current approaches for cancer immunotherapy to propose new preventive and therapeutic strategies for age-related diseases.

Keywords

Cellular senescence Age-related diseases Immune surveillance 

Notes

Acknowledgments

We are grateful to all the members of Krizhanovsky laboratory for insightful discussions. Y.O is supported by the German-Israeli Helmholtz Research School in Cancer Biology. V.K. is supported by grants from European Research Council under the European Union’s FP7; Israel Science Foundation; Ministry of Science, Technology & Space of the State of Israel and the German Cancer Research Center (DKFZ); Marie Curie International Reintegration Grant. V. K. is an incumbent of the Karl and Frances Korn Career Development Chair in Life Sciences.

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© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Molecular Cell BiologyThe Weizmann Institute of ScienceRehovotIsrael

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