Caloric restriction in humans reveals immunometabolic regulators of health span
| Autor: | 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 |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Male Aging Inflammasomes Longevity Down-Regulation Thymus Gland Article Mice NLR Family Pyrin Domain-Containing 3 Protein Animals Humans Caloric Restriction Inflammation Multidisciplinary Lymphopoiesis Macrophages Thermogenesis Middle Aged Mitochondria Adipose Tissue Immune System 1-Alkyl-2-acetylglycerophosphocholine Esterase Female Energy Metabolism Transcriptome |
| Zdroj: | Science |
| ISSN: | 1095-9203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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