T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
Gabriela Desdín-Micó, Gonzalo Soto‐Heredero, Juan Aranda, Jorge Oller, Elisa Carrasco, Enrique Gabandé‐Rodríguez, Eva María Blanco, Arántzazu Alfranca, Lorena Cussó, Manuel Desco, Borja Ibáñez, Arancha R. Gortázar, Pablo J. Fernández-Marcos, Marı́a N. Navarro, Bruno Hernáez, Antonio Alcamı́, Francesc Baixauli, Marı́a Mittelbrunn
Abstract
Inflammaging? Blame T cells! Mitochondrial dysfunction in various tissues is a prominent characteristic of age-related deterioration, but it is unclear how mitochondrial dysfunction in particular cell types contributes to this process. Desdín-Micó et al. generated mice with T cells that were specifically deficient in a mitochondrial DNA–stabilizing protein. These animals exhibited multiple features associated with aging, including neurological, metabolic, muscular, and cardiovascular impairments. The defective T cells initiated an inflammatory program similar to that observed in older animals, a process called “inflammaging.” Blocking the cytokine tumor necrosis factor–α or administering precursors of the cofactor nicotinamide adenine dinucleotide restored many of these symptoms of senescence. These findings may potentially inform future therapies for age-associated diseases, as well as cachexia and cytokine-release syndrome. Science , this issue p. 1371