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Cellular senescence in aging and age-related disease: from mechanisms to therapy

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Abstract

Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

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Figure 1: Effector pathways of three senescent cell types.
Figure 2: Senescence in aging, age-related diseases and disease-related treatments.
Figure 3: Senescent cells as drivers and amplifiers of disease.
Figure 4: Senotherapies to prevent disease and extend healthy life span.

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Acknowledgements

We are grateful to R. Naylor for reading the manuscript and providing helpful discussion. The US National Institutes of Health (J.M.v.D. R01CA96985 and AG41122-01P2), the Paul F. Glenn Foundation (D.J.B. and J.M.v.D.), the Ellison Medical Foundation (D.J.B.), and the Noaber Foundation (J.M.v.D.) provided financial support to the authors during the writing of the review.

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Childs, B., Durik, M., Baker, D. et al. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat Med 21, 1424–1435 (2015). https://doi.org/10.1038/nm.4000

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