炎症
长寿
线粒体生物发生
免疫系统
免疫学
医学
生物
脂肪组织
重编程
脂质代谢
内分泌学
基因
遗传学
作者
Olga Spadaro,Yun‐Hee Youm,Irina Shchukina,Seungjin Ryu,Sviatoslav Sidorov,Anthony Ravussin,Kim Nguyen,Ekaterina Aladyeva,Alexander V. Predeus,Steven R. Smith,Éric Ravussin,Craig J. Galbán,Maxim N. Artyomov,Vishwa Deep Dixit
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2022-02-10
卷期号:375 (6581): 671-677
被引量:166
标识
DOI:10.1126/science.abg7292
摘要
The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.
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