Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice

Noga Ron-Harel, Giulia Notarangelo, Jonathan M. Ghergurovich, Joao A. Paulo, Peter T. Sage, Daniel Santos, F. Kyle Satterstrom, Steven P. Gygi, Joshua D. Rabinowitz, Arlene H. Sharpe, Marcia C. Haigis

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


T cell-mediated immune responses are compromised in aged individuals, leading to increased morbidity and reduced response to vaccination. While cellular metabolism tightly regulates T cell activation and function, metabolic reprogramming in aged T cells has not been thoroughly studied. Here, we report a systematic analysis of metabolism during young versus aged naïve T cell activation. We observed a decrease in the number and activation of naïve T cells isolated from aged mice. While young T cells demonstrated robust mitochondrial biogenesis and respiration upon activation, aged T cells generated smaller mitochondria with lower respiratory capacity. Using quantitative proteomics, we defined the aged T cell proteome and discovered a specific deficit in the induction of enzymes of one-carbon metabolism. The activation of aged naïve T cells was enhanced by addition of products of one-carbon metabolism (formate and glycine). These studies define mechanisms of skewed metabolic remodeling in aged T cells and provide evidence that modulation of metabolism has the potential to promote immune function in aged individuals.

Original languageEnglish (US)
Pages (from-to)13347-13352
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number52
StatePublished - Dec 26 2018

All Science Journal Classification (ASJC) codes

  • General


  • Aging
  • Metabolism
  • Mitochondria
  • One-carbon metabolism
  • T cells


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