TitleDefective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice.
Publication TypeJournal Article
Year of Publication2018
AuthorsRon-Harel, N, Notarangelo, G, Ghergurovich, JM, Paulo, JA, Sage, PT, Santos, D, F Satterstrom, K, Gygi, SP, Rabinowitz, JD, Sharpe, AH, Haigis, MC
JournalProc Natl Acad Sci U S A
Date Published2018 12 26
KeywordsAge Factors, Animals, Carbon, CD4-Positive T-Lymphocytes, Female, Immunity, Cellular, Immunity, Innate, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mitochondria, Organelle Biogenesis, Respiration, T-Lymphocytes

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID30530686
PubMed Central IDPMC6310842
Grant ListR01 CA213062 / CA / NCI NIH HHS / United States
R01 GM067945 / GM / NIGMS NIH HHS / United States