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Senotherapy: growing old and staying young?

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Abstract

Cellular senescence, which has been linked to age-related diseases, occurs during normal aging or as a result of pathological cell stress. Due to their incapacity to proliferate, senescent cells cannot contribute to normal tissue maintenance and tissue repair. Instead, senescent cells disturb the microenvironment by secreting a plethora of bioactive factors that may lead to inflammation, regenerative dysfunction and tumor progression. Recent understanding of stimuli and pathways that induce and maintain cellular senescence offers the possibility to selectively eliminate senescent cells. This novel strategy, which so far has not been tested in humans, has been coined senotherapy or senolysis. In mice, senotherapy proofed to be effective in models of accelerated aging and also during normal chronological aging. Senotherapy prolonged lifespan, rejuvenated the function of bone marrow, muscle and skin progenitor cells, improved vasomotor function and slowed down atherosclerosis progression. While initial studies used genetic approaches for the killing of senescent cells, recent approaches showed similar effects with senolytic drugs. These observations open up exciting possibilities with a great potential for clinical development. However, before the integration of senotherapy into patient care can be considered, we need further research to improve our insight into the safety and efficacy of this strategy during short- and long-term use.

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  1. Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Roland Schmitt

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This study was supported by the German Research Foundation (DFG): CRC 738 and SCHM 2146/6-1.

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Schmitt, R. Senotherapy: growing old and staying young?. Pflugers Arch - Eur J Physiol 469, 1051–1059 (2017). https://doi.org/10.1007/s00424-017-1972-4

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