@article{2559,
  keywords = {Animals, Carbon, Female, Mice, Mice, Inbred C57BL, Mitochondria, Age Factors, Lymphocyte Activation, T-Lymphocytes, Immunity, Innate, Organelle Biogenesis, CD4-Positive T-Lymphocytes, Immunity, Cellular, Respiration},
  author = {Noga Ron-Harel and Giulia Notarangelo and Jonathan Ghergurovich and Joao Paulo and Peter Sage and Daniel Santos and Kyle Satterstrom and Steven Gygi and Joshua Rabinowitz and Arlene Sharpe and Marcia Haigis},
  title = {Defective respiration and one-carbon metabolism contribute to impaired na{\"\i}ve T cell activation in aged mice.},
  abstract = {<p>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 na{\"\i}ve T cell activation. We observed a decrease in the number and activation of na{\"\i}ve 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 na{\"\i}ve 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.</p>
},
  year = {2018},
  journal = {Proc Natl Acad Sci U S A},
  volume = {115},
  pages = {13347-13352},
  month = {12/2018},
  issn = {1091-6490},
  doi = {10.1073/pnas.1804149115},
  language = {eng},
}