1. T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
- Author
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Instituto de Salud Carlos III, European Commission, European Research Council, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Desdín-Mico, Gabriela, Soto-Heredero, Gonzalo, Aranda, Juan Francisco, Oller, Jorge, Carrasco, Elisa, Gabandé-Rodríguez, Enrique, Blanco, Eva M., Alfranca, Arantzazu, Cussó, Lorena, Desco, Manuel, Ibañez, Borja, Gortazar, Arancha R., Fernández-Marcos, Pablo, Navarro, María N., Hernaez, Bruno, Alcamí, Antonio, Baixauli, Francesc, Mittelbrunn, María, Instituto de Salud Carlos III, European Commission, European Research Council, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Desdín-Mico, Gabriela, Soto-Heredero, Gonzalo, Aranda, Juan Francisco, Oller, Jorge, Carrasco, Elisa, Gabandé-Rodríguez, Enrique, Blanco, Eva M., Alfranca, Arantzazu, Cussó, Lorena, Desco, Manuel, Ibañez, Borja, Gortazar, Arancha R., Fernández-Marcos, Pablo, Navarro, María N., Hernaez, Bruno, Alcamí, Antonio, Baixauli, Francesc, and Mittelbrunn, María
- Abstract
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-a 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.
- Published
- 2020