期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 52, 页码 13347-13352出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1804149115
关键词
metabolism; T cells; mitochondria; one-carbon metabolism; aging
资金
- F. Hoffmann-La Roche, Ltd.
- Glenn Foundation for Medical Research
- Ludwig Center at Harvard Medical School
- NIH [R01CA213062]
- European Molecular Biology Organization
- Israeli National Postdoctoral Award Program for Advancing Women In Science
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 naive T cell activation. We observed a decrease in the number and activation of naive 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 naive 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.
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