Caloric restriction in humans reveals immunometabolic regulators of health span.
Caloric restriction in humans reveals immunometabolic regulators of health span.
复制标题
人类的卡路里限制揭示了健康持续时间的免疫代谢调节。
DOI：
10.1126/science.abg7292
复制
发表时间：
2022-02-11
期刊：
影响因子：
56.9
通讯作者：
Dixit, V. D.
中科院分区：
文献类型：
--
作者：
Spadaro, O.;Youm, Y.;Shchukina, I;Ryu, S.;Sidorov, S.;Ravussin, A.;Nguyen, K.;Aladyeva, E.;Predeus, A. N.;Smith, S. R.;Ravussin, E.;Galban, C.;Artyomov, M. N.;Dixit, V. D.
啮齿动物中由40%热量限制（CR）驱动的寿命延长导致生长、繁殖和免疫防御的权衡，使得难以鉴定治疗相关的CR模拟靶标。我们报告说，约14%的CR为2年的健康人改善胸腺生成，并与动员胸腺内异位脂质。脂肪组织中CR诱导的转录重编程涉及调节线粒体生物能量学、抗炎反应和寿命的途径。在经历CR的人中，编码血小板活化因子乙酰水解酶（PLA2G7）的基因PLA2G7的表达被抑制。小鼠中Pla2g7的缺失显示胸腺脂肪萎缩减少，保护免受年龄相关性炎症，降低NLRP 3炎性小体活化，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，并可能被利用来降低炎症和延长健康寿命。
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.
登录
查看更多内容
影响因子：
7.7
作者：
Moll L;Roitenberg N;Bejerano-Sagie M;Boocholez H;Carvalhal Marques F;Volovik Y;Elami T;Siddiqui AA;Grushko D;Biram A;Lampert B;Achache H;Ravid T;Tzur YB;Cohen E
通讯作者：
Cohen E
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
克隆衍生的成年人类棕色脂肪细胞的遗传和功能表征。
影响因子：
82.9
作者：
Shinoda, Kosaku;Luijten, Ineke H. N.;Hasegawa, Yutaka;Hong, Haemin;Sonne, Si B.;Kim, Miae;Xue, Ruidan;Chondronikola, Maria;Cypess, Aaron M.;Tseng, Yu-Hua;Nedergaard, Jan;Sidossis, Labros S.;Kajimura, Shingo
通讯作者：
Kajimura, Shingo
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
4.8
作者：
Patel, Sonal A.;Chaudhari, Amol;Kondratov, Roman V.
通讯作者：
Kondratov, Roman V.