%0 Journal Article
%A Desdín-Micó, Gabriela
%A Soto-Heredero, Gonzalo
%A Aranda Gómez, Juan Francisco
%A Oller, Jorge
%A Carrasco, Elisa
%A Gabandé-Rodríguez, Enrique
%A Blanco, Eva Maria
%A Alfranca, Arantzazu
%A Cussó, Lorena
%A Desco, Manuel
%A Ibañez, Borja
%A Gortazar, Arancha
%A Fernández-Marcos, Pablo
%A Navarro, Maria 
%A Hernaez, Bruno
%A Alcamí, Antonio
%A Baixauli,  Francesc
%A Mittelbrunn, María
%T T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
%D 2020
%@ 0036-8075
%U https://hdl.handle.net/20.500.14352/95026
%X 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.
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