ArticleProceedings of the National Academy of Sciences of the United States of America2018
Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 138 citations in OpenAlex.
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- From Regenerative to Degenerative Niche: Multicellular Crosstalk and Population Dynamics in Skeletal Muscle Aging.Aging cell · 2026Review
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- Metabolic exhaustion and immune ageing in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- AFF3 maintains metabolic quiescence in naive CD8 T cells and prevents premature immune aging.JCI insight · 2026Article
- Metabolic determinants of cancer immunotherapy outcomes identified by plasma profiling.Nature medicine · 2026Article
- Targeting NFATc1-regulated MTHFD2 one-carbon metabolism to suppress sustained T-cell-mediated inflammation in rheumatoid arthritis.Signal transduction and targeted therapy · 2026Article
- CD8Science China. Life sciences · 2026Review
- Lifelong Exercise as a Modulator of CD4European journal of clinical investigation · 2026Review
- Single-cell profiling reveals immunometabolic remodeling with T-cell dysfunction in HIV-1 infected people.Infectious diseases & immunity · 2026Article
- Host Aging Induces a Senescent-Like Phenotype in Neutrophils and Altered Transcriptional Responses to Streptococcus pneumoniae.Aging cell · 2026Article
- B cells drive CD4 T cell immunosenescence and age-associated health decline.Science immunology · 2026Article
- Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Exploring the impact of DEP on pediatric Crohn's disease using machine learning and molecular docking methods.Frontiers in pediatrics · 2026Article
- Age-related reduction of pyruvate dehydrogenase kinase 1 impairs T cell responses.Frontiers in immunology · 2026Article
- Review
- A collagen amino acid composition supplementation reduces biological age in humans and increases health and lifespan in vivo.npj aging · 2025Article
- Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation.Nature aging · 2025Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.