Skip to main content

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

Author(s): Ron-Harel, Noga; Notarangelo, Giulia; Ghergurovich, Jonathan M; Paulo, Joao A; Sage, Peter T; et al

Download
To refer to this page use: http://arks.princeton.edu/ark:/88435/pr1x87z
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.
Publication Date: 10-Dec-2018
Citation: 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, Haigis, Marcia C. (2018). Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice. Proceedings of the National Academy of Sciences of the United States of America, 115 (52), 13347 - 13352. doi:10.1073/pnas.1804149115
DOI: doi:10.1073/pnas.1804149115
ISSN: 0027-8424
EISSN: 1091-6490
Pages: 13347 - 13352
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Proceedings of the National Academy of Sciences of the United States of America
Version: Final published version. This is an open access article.



Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.