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

Publication Year
2018

Type

Journal Article
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.

Journal
Proc Natl Acad Sci U S A
Volume
115
Issue
52
Pages
13347-13352
Date Published
12/2018
ISSN Number
1091-6490
Alternate Journal
Proc. Natl. Acad. Sci. U.S.A.
PMCID
PMC6310842
PMID
30530686