T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.

Journal: Science (New York, N.Y.)
Published:
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-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.

Authors
Gabriela Desdín Micó, Gonzalo Soto Heredero, Juan Aranda, Jorge Oller, Elisa Carrasco, Enrique Gabandé Rodríguez, Eva Blanco, Arantzazu Alfranca, Lorena Cussó, Manuel Desco, Borja Ibañez, Arancha Gortazar, Pablo Fernández Marcos, Maria Navarro, Bruno Hernaez, Antonio Alcamí, Francesc Baixauli, María Mittelbrunn