研究人员报道，在健康人中，约14%的CR持续2年，改善了胸腺造血功能，并与调动体内异位脂质相关。CR 诱导的脂肪组织转录重编程涉及调节线粒体生物能量、抗炎反应和寿命的途径。在经历CR的人类中，编码血小板活化因子乙酰水解酶 (PLA2G7) 的基因Pla2g7的表达受到抑制。小鼠中Pla2g7的缺失显示胸腺脂肪萎缩减少，防止与年龄相关的炎症，降低NLRP3炎症小体激活，并改善代谢健康。因此，PLA2G7的减少可能介导CR的免疫代谢作用，并可能被用于降低炎症和延长健康寿命。
据悉，在啮齿类动物中，40%的热量限制 (caloric restriction, CR)所驱动的寿命延长导致了生长、繁殖和免疫防御方面的权衡，从而难以确定治疗相关的CR模拟靶标。
附：英文原文
Title: Caloric restriction in humans reveals immunometabolic regulators of health span
Author: O. Spadaro, Y. Youm, I. Shchukina, S. Ryu, S. Sidorov, A. Ravussin, K. Nguyen, E. Aladyeva, A. N. Predeus, S. R. Smith, E. Ravussin, C. Galban, M. N. Artyomov, V. D. Dixit
Issue&Volume: 2022-02-11
Abstract: 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.
DOI: abg7292
Source: https://www.science.org/doi/10.1126/science.abg7292