ArticleThe Journal of clinical investigation2021
Histone deficiency and accelerated replication stress in T cell aging.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Lactylation in influenza a virus infection: Current evidence, knowledge gaps, and future perspectives.Virulence · 2026Review
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- The immunology behind inflammaging-causes, sources, and mechanisms.The Journal of allergy and clinical immunology · 2026Review
- Antigen-specific TScience advances · 2026Article
- Article
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- In Silico Analysis of MiRNA Regulatory Networks to Identify Potential Biomarkers for the Clinical Course of Viral Infections.International journal of molecular sciences · 2025Article
- Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges.Journal of hematology & oncology · 2025Review
- SIRT7 regulates NUCKS1 chromatin binding to elicit metabolic and inflammatory gene expression in senescence and liver aging.Molecular cell · 2025Article
- Meta-epigenetic shifts in T cell aging and aging-related dysfunction.Journal of biomedical science · 2025Review
- Sustained mTORC1 activation in activated T cells impairs vaccine responses in older individuals.Science advances · 2025Article
- BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress.Nature communications · 2025Article
- Metabolic Signaling as a Driver of T Cell Aging.Immune network · 2025Review
- The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression.npj aging · 2024Review
- T-Cell Senescence in Human Metabolic Diseases.Diabetes & metabolism journal · 2024Review
- Article
- Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity.PLoS pathogens · 2024Article
- Unraveling Histone Loss in Aging and Senescence.Cells · 2024Review
- Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis.Frontiers in aging · 2024Article
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
With increasing age, individuals are more vulnerable to viral infections such as with influenza or the SARS-CoV-2 virus. One age-associated defect in human T cells is the reduced expression of miR-181a. miR-181ab1 deficiency in peripheral murine T cells causes delayed viral clearance after infection, resembling human immune aging. Here we show that naive T cells from older individuals as well as miR-181ab1-deficient murine T cells develop excessive replication stress after activation, due to reduced histone expression and delayed S-phase cell cycle progression. Reduced histone expression was caused by the miR-181a target SIRT1 that directly repressed transcription of histone genes by binding to their promoters and reducing histone acetylation. Inhibition of SIRT1 activity or SIRT1 silencing increased histone expression, restored cell cycle progression, diminished the replication-stress response, and reduced the production of inflammatory mediators in replicating T cells from old individuals. Correspondingly, treatment with SIRT1 inhibitors improved viral clearance in mice with miR-181a-deficient T cells after LCMV infection. In conclusion, SIRT1 inhibition may be beneficial to treat systemic viral infection in older individuals by targeting antigen-specific T cells that develop replication stress due to miR-181a deficiency.
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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.