Desdín-Micó, GabrielaSoto-Heredero, GonzaloAranda Gómez, Juan FranciscoOller, JorgeCarrasco, ElisaGabandé-Rodríguez, EnriqueBlanco, Eva MariaAlfranca, ArantzazuCussó, LorenaDesco, ManuelIbañez, BorjaGortazar, AranchaFernández-Marcos, PabloNavarro, MariaHernaez, BrunoAlcamí, AntonioBaixauli, FrancescMittelbrunn, María2024-01-242024-01-242020Gabriela Desdín-Micó et al. ,T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.Science368,1371-1376(2020).DOI:10.1126/science.aax08600036-807510.1126/science.aax0860https://hdl.handle.net/20.500.14352/95026This study was supported by the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI16/02188 and PI19/00855; and 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 (CPII 19/00014). 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.engjournal articlehttps://doi.org/10.1126/science.aax0860restricted access576.11Biología celular (Biología)2412 Inmunología2407 Biología Celular