2026-06-14T03:39:39Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/107212024-09-27T09:58:00Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Desdín-Micó, Gabriela author Soto-Heredero, Gonzalo author Aranda, Juan Francisco author Oller, Jorge author Carrasco, Elisa author Gabandé-Rodríguez, Enrique author Blanco, Eva Maria author Alfranca, Arantzazu author Cusso, Lorena author Desco, Manuel author Ibáñez, Borja author Gortazar, Arancha R author Fernández-Marcos, Pablo author Navarro, Maria N author Hernaez, Bruno author Alcamí, Antonio author Baixauli, Francesc author Mittelbrunn, María author 2020-06 The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result in premature death. T cell metabolic failure induces the accumulation of circulating cytokines, which resembles the chronic inflammation that is characteristic of aging ("inflammaging"). This cytokine storm itself acts as a systemic inducer of senescence. Blocking tumor necrosis factor-α signaling or preventing senescence with nicotinamide adenine dinucleotide precursors partially rescues premature aging in mice with Tfam-deficient T cells. Thus, T cells can regulate organismal fitness and life span, which highlights the importance of tight immunometabolic control in both aging and the onset of age-associated diseases. Science. 2020; 368(6497):1371-1376 10.1126/science.aax0860 1095-9203 Science (New York, N.Y.) 32439659 http://hdl.handle.net/20.500.12105/10721 T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.