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Immunosurveillance of senescent cells: the bright side of the senescence program

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Abstract

Cellular senescence, a state of irreversible cell cycle arrest, is a robust mechanism used to mediate tumor suppression and control the tissue damage response following short-term insults. In addition, the senescence associated-secretory phenotype (SASP), one of the most profound characteristics of the senescence program, facilitates the immunosurveillance of senescent cells. The SASP includes many chemokines, cytokines and adhesion molecules that can recruit and activate distinct immune cells from both the innate and adaptive immune system such as NK cells, monocytes/macrophages and T cells. Furthermore, senescent cells can upregulate specific immune ligands on their cell surface that can mediate the recognition of these cells by specific immune cell subsets and lead to activation of the immune cells. Consequently, the activated immune cells engage explicit regulatory mechanisms to eliminate senescent cells. For example, recent work from our laboratory showed that perforin-granzyme exocytosis mediates NK-cell killing of senescent cells. Here, we summarize the current advances in our knowledge of the mechanisms underlying specific immune-mediated elimination of senescent cells.

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Acknowledgments

We are grateful to D. Burton for insightful comments and to other members of the Krizhanovsky lab for helpful discussions. This work was supported by grants to V. K. from European Research Council under the European Union’s FP7 (ERC grant n 309688), from Israel Science Foundation and from DKFZ-MOST program. V. K. is an incumbent of the Karl and Frances Korn Career Development Chair in Life Sciences.

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  1. Department of Molecular Cell Biology, Weizmann Institute of Science, 76100, Rehovot, Israel

    Adi Sagiv & Valery Krizhanovsky

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  1. Adi Sagiv
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  2. Valery Krizhanovsky
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Correspondence to Valery Krizhanovsky.

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Sagiv, A., Krizhanovsky, V. Immunosurveillance of senescent cells: the bright side of the senescence program. Biogerontology 14, 617–628 (2013). https://doi.org/10.1007/s10522-013-9473-0

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