Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice. Author Noga Ron-Harel, Giulia Notarangelo, Jonathan Ghergurovich, Joao Paulo, Peter Sage, Daniel Santos, Kyle Satterstrom, Steven Gygi, Joshua Rabinowitz, Arlene Sharpe, Marcia Haigis Publication Year 2018 Type Journal Article Abstract 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. 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 Journal Proc Natl Acad Sci U S A Volume 115 Issue 52 Pages 13347-13352 Date Published 12/2018 ISSN Number 1091-6490 DOI 10.1073/pnas.1804149115 Alternate Journal Proc. Natl. Acad. Sci. U.S.A. PMCID PMC6310842 PMID 30530686 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML