Loss of Pla2r1 decreases cellular senescence and age‐related alterations caused by aging and Western diets

Cellular senescence is induced by many stresses including telomere shortening, DNA damage, oxidative, or metabolic stresses. Senescent cells are stably cell cycle arrested and they secrete many factors including cytokines and chemokines. Accumulation of senescent cells promotes many age‐related alterations and diseases. In this study, we investigated the role of the pro‐senescent phospholipase A2 receptor 1 (PLA2R1) in regulating some age‐related alterations in old mice and in mice subjected to a Western diet, whereas aged wild‐type mice displayed a decreased ability to regulate their glycemia during glucose and insulin tolerance tests, aged Pla2r1 knockout (KO) mice efficiently regulated their glycemia and displayed fewer signs of aging. Loss of Pla2r1 was also found protective against the deleterious effects of a Western diet. Moreover, these Pla2r1 KO mice were partially protected from diet‐induced senescent cell accumulation, steatosis, and fibrosis. Together these results support that Pla2r1 drives several age‐related alterations, especially in the liver, arising during aging or through a Western diet.

Keywords

aging cellular senescence liver Western diet ALP alkaline phosphatase CD chow diet COPD chronic obstructive pulmonary diseases DEGs differentially expressed genes FA fatty acids H&E hematoxylin and eosin HSCs hepatic stellate cells HSC hematopoietic stem cells IHC immunohistochemistry IPGTT intraperitoneal glucose tolerance test KO knock-out NAFLD nonalcoholic fatty liver disease NASH nonalcoholic steatohepatitis PLA2R1 phospholipase A2 receptor 1 ROS reactive oxygen species SASP senescence-associated secretory phenotype scRNA-seq single-cell RNA-sequencing SPF specific-pathogen-free TG triglycerides WD western diet WT wild-type alkaline phosphatase CD chow diet COPD chronic obstructive pulmonary diseases DEGs differentially expressed genes FA fatty acids H&E hematoxylin and eosin HSCs hepatic stellate cells HSC hematopoietic stem cells IHC immunohistochemistry IPGTT intraperitoneal glucose tolerance test KO knock-out NAFLD nonalcoholic fatty liver disease NASH nonalcoholic steatohepatitis PLA2R1 phospholipase A2 receptor 1 ROS reactive oxygen species SASP senescence-associated secretory phenotype scRNA-seq single-cell RNA-sequencing SPF specific-pathogen-free TG triglycerides WD western diet WT

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Geriatry and gerontology

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Submitted on : Monday, October 2, 2023-5:58:41 PM

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hal-04225404 , version 1 (02-10-2023)

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HAL Id : hal-04225404 , version 1
DOI : 10.1111/acel.13971
PUBMED : 37667516
WOS : 001061841600001

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Amélie Massemin, Delphine Goehrig, Jean‐michel Flaman, Sara Jaber, Audrey Griveau, et al.. Loss of Pla2r1 decreases cellular senescence and age‐related alterations caused by aging and Western diets. Aging Cell, 2023, ⟨10.1111/acel.13971⟩. ⟨hal-04225404⟩

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