Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis

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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

1 Citaat (Scopus)

Samenvatting

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.

Originele taal-2English
TijdschriftCell metabolism
DOI's
StatusE-pub ahead of print - 2021

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