puc-header

Prostaglandin Biosynthesis Reinforces Cellular Senescence Through a RAS/p53 Feedback Loop and Allows Detection of Senolysis

41 Pages Posted: 4 Feb 2020 Publication Status: Review Complete

See all articles by Christopher Dean Wiley

Christopher Dean Wiley

Buck Institute for Research on Aging

Rishi Sharma

Buck Institute for Research on Aging

Sonnet S. Davis

Denali Therapeutics; Buck Institute for Research on Aging

Jose Alberto Lopez-Dominguez

Buck Institute for Research on Aging

Kylie P. Mitchell

Buck Institute for Research on Aging

Samantha Wiley

Buck Institute for Research on Aging

Fatouma Alimirah

Buck Institute for Research on Aging

Dong Eun Kim

Buck Institute for Research on Aging

Therese Payne

Buck Institute for Research on Aging

Marco Demaria

Buck Institute for Research on Aging

Arvind Ramanathan

Buck Institute for Research on Aging

Judith Campisi

Buck Institute for Research on Aging; University of California, Berkeley - Lawrence Berkeley National Laboratory (Berkeley Lab)

More...

Abstract

SummaryCellular senescence is a stress or damage response that results in 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 have been understudied. We show that senescent cells activate the biosynthesis of several eicosanoids that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2, which, together with other prostaglandin D2 derivatives, promote the senescence arrest and SASP by activating RAS signaling. Further, 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. These data identify an important new aspect of cellular senescence and a novel method to detect senolysis.

Keywords: cellular senescence, senescence, aging, lipids, metabolomics, eicosanoid, SASP, prostaglandin, dihomo-prostaglandin, biomarker, mass spectrometry, 15d-PGJ2

Suggested Citation

Wiley, Christopher Dean and Sharma, Rishi and Davis, Sonnet S. and Lopez-Dominguez, Jose Alberto and Mitchell, Kylie P. and Wiley, Samantha and Alimirah, Fatouma and Kim, Dong Eun and Payne, Therese and Demaria, Marco and Ramanathan, Arvind and Campisi, Judith, Prostaglandin Biosynthesis Reinforces Cellular Senescence Through a RAS/p53 Feedback Loop and Allows Detection of Senolysis. Available at SSRN: https://ssrn.com/abstract=3528689 or http://dx.doi.org/10.2139/ssrn.3528689
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Christopher Dean Wiley

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Rishi Sharma

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Sonnet S. Davis

Denali Therapeutics ( email )

United States

Buck Institute for Research on Aging ( email )

8001 Redwood Boulevard
Novato, CA 94945
United States

Jose Alberto Lopez-Dominguez

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Kylie P. Mitchell

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Samantha Wiley

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Fatouma Alimirah

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Dong Eun Kim

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Therese Payne

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Marco Demaria

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Arvind Ramanathan

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

Judith Campisi (Contact Author)

Buck Institute for Research on Aging

8001 Redwood Boulevard
Novato, CA 94945
United States

University of California, Berkeley - Lawrence Berkeley National Laboratory (Berkeley Lab)

1 Cyclotron Road
Berkeley, CA 94720
United States

Click here to go to Cell.com

Paper statistics

Abstract Views
353
Downloads
23