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bioRxiv · 10.1101/2023.09.20.558729

ASK1 promotes inflammation in senescence and aging

Odawara, T.·Yamauchi, S.·Ichijo, H.
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Abstract

Cellular senescence is a stress-induced, permanent cell cycle arrest involved in tumor suppression and aging. Senescent cells secrete bioactive molecules such as pro-inflammatory cytokines and chemokines. This senescence-associated secretory phenotype (SASP) has been implicated in immune-mediated elimination of senescent cells and age-associated chronic inflammation. However, the mechanisms regulating the SASP are incompletely understood. Here, we show that the stress-responsive kinase ASK1 promotes inflammation in senescence and aging. ASK1 is activated during senescence and increases the expression of pro-inflammatory cytokines and chemokines by activating p38, a kinase critical for the SASP. ASK1-deficient mice show impaired elimination of oncogene-induced senescent cells and an increased rate of tumorigenesis. Furthermore, ASK1 deficiency prevents age-associated p38 activation and inflammation and attenuates glomerulosclerosis. Our results suggest that ASK1 is a driver of the SASP and age-associated chronic inflammation and represents a potential therapeutic target for age-related diseases.

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Odawara, T., Yamauchi, S., Ichijo, H.. 2023-09-21. ASK1 promotes inflammation in senescence and aging. https://doi.org/10.1101/2023.09.20.558729

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