2026-06-27T22:27:39Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/950262025-03-18T13:29:58Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Desdín-Micó, Gabriela author Soto-Heredero, Gonzalo author Aranda Gómez, Juan Francisco author Oller, Jorge author Carrasco, Elisa author Gabandé-Rodríguez, Enrique author Blanco, Eva Maria author Alfranca, Arantzazu author Cussó, Lorena author Desco, Manuel author Ibañez, Borja author Gortazar, Arancha author Fernández-Marcos, Pablo author Navarro, Maria author Hernaez, Bruno author Alcamí, Antonio author Baixauli, Francesc author Mittelbrunn, María 2024-01-24T10:34:51Z 2024-01-24T10:34:51Z 2020 Gabriela Desdín-Micó et al. ,T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.Science368,1371-1376(2020).DOI:10.1126/science.aax0860 0036-8075 10.1126/science.aax0860 https://hdl.handle.net/20.500.14352/95026 https://doi.org/10.1126/science.aax0860 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. eng T cells with dysfunctional mitochondria induce multimorbidity and premature senescence journal article 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 URL https://docta.ucm.es/bitstreams/b18a23d6-3bb3-48fc-b1a5-4f20d2322b10/download File MD5 11670b74dc0999a64a7a4304c3812a8b 1606597 application/pdf T_cells_with_dysfunctional_mitochondria.pdf URL https://docta.ucm.es/bitstreams/0d53aebc-af51-4345-926e-b07fdc269d51/download File MD5 0e8f3499e4fbdbf5e977d795cee00c50 32400 text/plain T_cells_with_dysfunctional_mitochondria.pdf.txt