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


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.

SUBMITTER: Ron-Harel N 

PROVIDER: S-EPMC6310842 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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

Ron-Harel Noga N   Notarangelo Giulia G   Ghergurovich Jonathan M JM   Paulo Joao A JA   Sage Peter T PT   Santos Daniel D   Satterstrom F Kyle FK   Gygi Steven P SP   Rabinowitz Joshua D JD   Sharpe Arlene H AH   Haigis Marcia C MC  

Proceedings of the National Academy of Sciences of the United States of America 20181210 52


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 cel  ...[more]

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