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Cellular senescence: a view throughout organismal life

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Abstract

Cellular senescence is the final fate of most cells in response to specific stimuli, but is not the end. Indeed, it is the beginning of a singular life, with multiple side roads leading to diverse effects on the organism. Many studies have been done in the last few years to elucidate the intriguing role of senescent cells in the organism, demonstrating them as the cause of several age-related diseases. However, these cells are also positively implicated in other important pathways, such as embryogenesis and wound healing. It appears that the multiple effects are time-dependent: long-term senescence is mostly implicated in chronic inflammation and disease, whereas in the short term, senescent cells seem to be beneficial, being rapidly targeted by the innate immune system. The influence of senescent cells on their neighbors by paracrine factors, differential activity depending on developmental stage, and duration of the effects make the cellular senescent program a unique spatial–temporal mechanism. During pathological conditions such as progeroid syndromes, this mechanism is deregulated, leading to accelerated onset of some aging-related diseases and a shorter lifespan, among other physiological defects. Here, we review the three primary cell senescence programs described so far (replicative, stress-induced, and developmentally programmed senescence), their onset during development, and their potential roles in diseases with premature aging. Finally, we discuss the role of immune cells in keeping senescence burden below the threshold of disease.

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Acknowledgements

I am grateful to Carlos López-Otín, Patricia L. Opresko, Ignacio Flores, and Jeanine Harrigan for their helpful comments on the manuscript. I also thank Adrián V. and Victoria C. for their productive discussions and support. The professional editing service NB Revisions was used for technical editing of the manuscript prior to submission.

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  1. Centro de Biología Molecular “Severo Ochoa” (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid, 28049, Madrid, Spain

    Cayetano von Kobbe

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von Kobbe, C. Cellular senescence: a view throughout organismal life. Cell. Mol. Life Sci. 75, 3553–3567 (2018). https://doi.org/10.1007/s00018-018-2879-8

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