Desdín-Micó, GabrielaSoto-Heredero, GonzaloAranda, Juan FranciscoOller, JorgeCarrasco, ElisaGabandé-Rodríguez, EnriqueBlanco, Eva MariaAlfranca, ArantzazuCusso, LorenaDesco, ManuelIbáñez, BorjaGortazar, Arancha RFernández-Marcos, PabloNavarro, Maria NHernaez, BrunoAlcamí, AntonioBaixauli, FrancescMittelbrunn, María2020-07-082020-07-082020-06Science. 2020; 368(6497):1371-1376http://hdl.handle.net/20.500.12105/10721This study was supported by the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI16/188, PI19/855, as well as PI16/02110 to B.I.), the European Regional Development Fund (ERDF), and the European Commission through H2020-EU.1.1 and European Research Council grant ERC-2016-StG 715322-EndoMitTalk. This work was partially supported by Comunidad de Madrid (S2017/BMD-3867 RENIM-CM). M.M. is supported by the Miguel Servet Program (CP 19/014). G.S.-H. is supported by FPI-UAM, J.O (FJCI-2017-33855) and E.G-R (IJC2018-036850) by Juan de la Cierva, and E.C. by Atracción de Talento Investigador 2017-T2/BMD-5766 (Comunidad de Madrid and UAM). B.I. was supported by ERC research grant ERC-2018-CoG 819775-MATRIX.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.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internacional3243965936864971371-137610.1126/science.aax08601095-9203Science (New York, N.Y.)open access