@article{3521,
  keywords = {Animals, Mice, Mice, Inbred C57BL, Female, Immunity, Innate, Mitochondria, Carbon, Organelle Biogenesis, T-Lymphocytes, Age Factors, CD4-Positive T-Lymphocytes, Immunity, Cellular, Lymphocyte Activation, Respiration},
  author = {Noga Ron-Harel and Giulia Notarangelo and Jonathan Ghergurovich and Joao Paulo and Peter Sage and Daniel Santos and F 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 = {2018 Dec 26},
  issn = {1091-6490},
  doi = {10.1073/pnas.1804149115},
  language = {eng},
}