T cells with dysfunctional mitochondria induce multimorbidity and premature senescence Articles uri icon


  • Desdin-Mico, Gabriela
  • Soto-Heredero, Gonzalo
  • Aranda, Juan Francisco
  • Oller, Jorge
  • Carrasco, Elisa
  • Gabande-Rodriguez, Enrique
  • Blanco, Eva Maria
  • Alfranca, Arantzazu
  • Ibanez, Borja
  • Gortazar, Arancha R.
  • Fernandez-Marcos, Pablo
  • Navarro, Maria N.
  • Hernaez, Bruno
  • Alcami, Antonio
  • Baixauli, Francesc
  • Mittelbrunn, Maria

publication date

  • June 2020

start page

  • 1371

end page

  • 1376


  • 6497


  • 368

International Standard Serial Number (ISSN)

  • 0036-8075

Electronic International Standard Serial Number (EISSN)

  • 1095-9203


  • 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-ɑ 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.