TY - JOUR T1 - Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis. JF - Cell Metab Y1 - 2021 A1 - Wiley, Christopher D A1 - Sharma, Rishi A1 - Davis, Sonnet S A1 - Lopez-Dominguez, Jose Alberto A1 - Mitchell, Kylie P A1 - Wiley, Samantha A1 - Alimirah, Fatouma A1 - Kim, Dong Eun A1 - Payne, Therese A1 - Rosko, Andrew A1 - Aimontche, Eliezer A1 - Deshpande, Sharvari M A1 - Neri, Francesco A1 - Kuehnemann, Chisaka A1 - Demaria, Marco A1 - Ramanathan, Arvind A1 - Campisi, Judith AB -

Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation, and many age-related pathologies. By contrast, lipid components of the SASP are understudied. 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.

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