Authors: Noga Ron-Harel, Giulia Notarangelo, Jonathan M. Ghergurovich, Joao A. Paulo, Peter T. Sage, Daniel Santos, F. Kyle Satterstrom, Steven P. Gygi, Joshua D. Rabinowitz, Arlene H. Sharpe, Marcia C. Haigis
Summary: 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.
Source: Proceedings of the National Academy of Sciences, 2018; 201804149