1. Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice.
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Ron-Harel, Noga, Notarangelo, Giulia, Ghergurovich, Jonathan M., Paulo, Joao A., Sage, Peter T., Santos, Daniel, Satterstrom, F. Kyle, Gygi, Steven P., Rabinowitz, Joshua D., Sharpe, Arlene H., and Haigis, Marcia C.
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T cells , *CELL respiration , *CARBON metabolism , *BIOTRANSFORMATION (Metabolism) , *MICE physiology , *MAMMAL aging , *IMMUNE response , *MITOCHONDRIA formation - 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 onecarbon 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. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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