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

• Published in: Aging cell Vol. 22; no. 11; p. e13971
• Main Authors: Massemin, Amélie, Goehrig, Delphine, Flaman, Jean‐Michel, Jaber, Sara, Griveau, Audrey, Djebali, Sophia, Marcos, Elisabeth, Payen, Léa, Marvel, Jacqueline, Parent, Romain, Adnot, Serge, Bertolino, Philippe, Rieusset, Jennifer, Tortereau, Antonin, Vindrieux, David, Bernard, David
• Format: Journal Article
• Language: English
• Published: London John Wiley & Sons, Inc 01.11.2023; Wiley Open Access
• Subjects: Age; Aging; Blood glucose; Bone marrow; Cell cycle; Chemokines; Chronic illnesses; Diet; DNA damage; Fibrosis; Geriatry and gerontology; Glucose; Glucose tolerance; Homeostasis; Human health and pathology; Leukocytes; Life Sciences; Liver diseases; Lymphatic system; Lymphocytes; Memory; Metabolic disorders; Phospholipase A2; Senescence; Spleen; Steatosis; Stem cells; Telomeres; specific-pathogen-free TG; ALP; IHC; differentially expressed genes FA; alkaline phosphatase CD; fatty acids H&E; SPF; western diet WT; SASP; senescence-associated secretory phenotype scRNA-seq; nonalcoholic steatohepatitis; reactive oxygen species SASP; scRNA-seq; cellular senescence; HSC; alkaline phosphatase; nonalcoholic steatohepatitis PLA2R1; hepatic stellate cells; liver; specific-pathogen-free; H&E; hematopoietic stem cells IHC; chronic obstructive pulmonary diseases; IPGTT; intraperitoneal glucose tolerance test; single-cell RNA-sequencing; nonalcoholic fatty liver disease; ROS; FA; phospholipase A2 receptor 1 ROS; PLA2R1; Western diet; immunohistochemistry IPGTT; nonalcoholic fatty liver disease NASH; NAFLD; senescence-associated secretory phenotype; knock-out; WD; knock-out NAFLD; DEGs; chronic obstructive pulmonary diseases DEGs; triglycerides WD; reactive oxygen species; intraperitoneal glucose tolerance test KO; immunohistochemistry; WT; chow diet; hematoxylin and eosin; CD; fatty acids; KO; hematoxylin and eosin HSCs; single-cell RNA-sequencing SPF; differentially expressed genes; triglycerides; NASH; TG; hepatic stellate cells HSC; HSCs; aging; wild-type; hematopoietic stem cells; chow diet COPD; phospholipase A2 receptor 1; COPD
• ISSN: 1474-9718; 1474-9726; 1474-9726; 1474-9728
• DOI: 10.1111/acel.13971

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.