Oxylipin Biosynthesis Reinforces Cellular Senescence and Allows Detection of Senolysis

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2021 Apr 3

PMID 33811820

Citations 64

Authors

Christopher D Wiley

Rishi Sharma

Sonnet S Davis

Jose Alberto Lopez-Dominguez

Kylie P Mitchell

Samantha Wiley

Fatouma Alimirah

Dong Eun Kim

Therese Payne

Andrew Rosko

Eliezer Aimontche

Sharvari M Deshpande

Francesco Neri

Chisaka Kuehnemann

Marco Demaria

Arvind Ramanathan

Judith Campisi

Affiliations

Soon will be listed here.

Abstract

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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