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Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis
Christopher D Wiley 1, Rishi Sharma 2, Sonnet S Davis 2, Jose Alberto Lopez-Dominguez 2, Kylie P Mitchell 2, Samantha Wiley 2, Fatouma Alimirah 2, Dong Eun Kim 2, Therese Payne 2, Andrew Rosko 2, Eliezer Aimontche 2, Sharvari M Deshpande 2, Francesco Neri 2, Chisaka Kuehnemann 2, Marco Demaria 3, Arvind Ramanathan 4, Judith Campisi 5
Abstract:
...We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis.
PMID: 33811820
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501892/
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