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

doi:10.1016/j.cmet.2021.03.008

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	1124-1136.e5
Number of pages	14
Journal	Cell Metabolism
Volume	33
Issue number	6
Early online date	2021
DOIs	https://doi.org/10.1016/j.cmet.2021.03.008
Publication status	Published - Jun-2021

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Wiley, C. D., Sharma, R., Davis, S. S., Lopez-Dominguez, J. A., Mitchell, K. P., Wiley, S., Alimirah, F., Kim, D. E., Payne, T., Rosko, A., Aimontche, E., Deshpande, S. M., Neri, F., Kuehnemann, C., Demaria, M., Ramanathan, A., & Campisi, J. (2021). Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis. Cell Metabolism, 33(6), 1124-1136.e5. https://doi.org/10.1016/j.cmet.2021.03.008

@article{38ef1b6fa5e746498d98be9cf70acc68,

title = "Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis",

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.",

author = "Wiley, {Christopher D} and Rishi Sharma and Davis, {Sonnet S} and Lopez-Dominguez, {Jose Alberto} and Mitchell, {Kylie P} and Samantha Wiley and Fatouma Alimirah and Kim, {Dong Eun} and Therese Payne and Andrew Rosko and Eliezer Aimontche and Deshpande, {Sharvari M} and Francesco Neri and Chisaka Kuehnemann and Marco Demaria and Arvind Ramanathan and Judith Campisi",

note = "Copyright {\textcopyright} 2021. Published by Elsevier Inc.",

year = "2021",

month = jun,

doi = "10.1016/j.cmet.2021.03.008",

language = "English",

volume = "33",

pages = "1124--1136.e5",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "6",

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Wiley, CD, Sharma, R, Davis, SS, Lopez-Dominguez, JA, Mitchell, KP, Wiley, S, Alimirah, F, Kim, DE, Payne, T, Rosko, A, Aimontche, E, Deshpande, SM, Neri, F, Kuehnemann, C, Demaria, M, Ramanathan, A & Campisi, J 2021, 'Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis', Cell Metabolism, vol. 33, no. 6, pp. 1124-1136.e5. https://doi.org/10.1016/j.cmet.2021.03.008

TY - JOUR

T1 - Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis

AU - Wiley, Christopher D

AU - Sharma, Rishi

AU - Davis, Sonnet S

AU - Lopez-Dominguez, Jose Alberto

AU - Mitchell, Kylie P

AU - Wiley, Samantha

AU - Alimirah, Fatouma

AU - Kim, Dong Eun

AU - Payne, Therese

AU - Rosko, Andrew

AU - Aimontche, Eliezer

AU - Deshpande, Sharvari M

AU - Neri, Francesco

AU - Kuehnemann, Chisaka

AU - Demaria, Marco

AU - Ramanathan, Arvind

AU - Campisi, Judith

PY - 2021/6

Y1 - 2021/6

N2 - 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.

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.

U2 - 10.1016/j.cmet.2021.03.008

DO - 10.1016/j.cmet.2021.03.008

M3 - Article

C2 - 33811820

SN - 1550-4131

VL - 33

SP - 1124-1136.e5

JO - Cell Metabolism

JF - Cell Metabolism

IS - 6

ER -

Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis

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