Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, Lyon, France.
Equipe Labellisée la Ligue Contre le Cancer, Lyon, France.
Aging Cell. 2023 Nov;22(11):e13971. doi: 10.1111/acel.13971. Epub 2023 Sep 4.
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.
细胞衰老可由多种应激诱导，包括端粒缩短、DNA 损伤、氧化或代谢应激。衰老细胞稳定地细胞周期停滞，并分泌多种因子，包括细胞因子和趋化因子。衰老细胞的积累会促进许多与年龄相关的改变和疾病。在这项研究中，我们研究了促衰老的磷脂酶 A2 受体 1（PLA2R1）在调节老年小鼠和西方饮食小鼠的一些与年龄相关的改变中的作用，而年龄大的野生型小鼠在葡萄糖和胰岛素耐量试验中调节血糖的能力下降，年老的 Pla2r1 敲除（KO）小鼠有效地调节血糖，并且表现出较少的衰老迹象。PLA2R1 的缺失也被发现对西方饮食的有害影响具有保护作用。此外，这些 Pla2r1 KO 小鼠对饮食诱导的衰老细胞积累、脂肪变性和纤维化具有部分保护作用。这些结果表明，PLA2R1 驱动着几种与年龄相关的改变，特别是在肝脏中，这些改变发生在衰老过程中或通过西方饮食发生。
