TY - JOUR
T1 - Caloric restriction in humans reveals immunometabolic regulators of health span
AU - Spadaro, O.
AU - Youm, Y.
AU - Shchukina, I.
AU - Ryu, S.
AU - Sidorov, S.
AU - Ravussin, A.
AU - Nguyen, K.
AU - Aladyeva, E.
AU - Predeus, A. N.
AU - Smith, S. R.
AU - Ravussin, E.
AU - Galban, C.
AU - Artyomov, M. N.
AU - Dixit, V. D.
N1 - Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.
PY - 2022/2/11
Y1 - 2022/2/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85124446034&partnerID=8YFLogxK
U2 - 10.1126/science.abg7292
DO - 10.1126/science.abg7292
M3 - Article
C2 - 35143297
AN - SCOPUS:85124446034
SN - 0036-8075
VL - 375
SP - 671
EP - 677
JO - Science
JF - Science
IS - 6581
ER -