Mechanisms underlying T cell ageing

Goronzy, Jörg J.; Weyand, Cornelia M.

doi:10.1038/s41577-019-0180-1

Cited by 508T-cell and B-cell ImmunologyTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

Mechanisms underlying T cell ageing

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Goronzy, Jörg J., Weyand, Cornelia M.·2019·Nature Reviews Immunology

DOI 10.1038/s41577-019-0180-1PMC PMC7584388

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Abstract

T cell ageing has a pivotal role in rendering older individuals vulnerable to infections and cancer and in impairing the response to vaccination. Easy accessibility to peripheral human T cells as well as an expanding array of tools to examine T cell biology have provided opportunities to examine major ageing pathways and their consequences for T cell function. Here, we review emerging concepts of how the body attempts to maintain a functional T cell compartment with advancing age, focusing on three fundamental domains of the ageing process, namely self-renewal, control of cellular quiescence and cellular senescence. Understanding these critical elements in successful T cell ageing will allow the design of interventions to prevent or reverse ageing-related T cell failure.

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Differences between mouse and human immune-ageing have been discovered, such as in mechanisms controlling naive T cell repertoire diversity.
“While mouse studies allow us to glean information on immunosenescence, differences between mouse and human immune-ageing have already been discovered, such as in mechanisms controlling naive T cell repertoire diversity135.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [135]
The NFκB, C/EBPβ, and cGAS-STING pathways play a key role in the induction of T cell senescence.
“The NFκB, C/EBPβ, and cGAS-STING pathways also play a key role in the induction of T cell senescence [66].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [66]
Memory T cells gradually accumulate with age.
“Some studies also documented that memory T cells gradually accumulate with age [66, 97–99].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [66]

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Virtual memory CD8 T cells display unique functional properties
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Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans
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Heterochromatin and its Relationship to Cell Senescence and Cancer Therapy
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Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux
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Concise Review: Age-Related Clonal Hematopoiesis: Stem Cells Tempting the Devil
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“Traditionally, it is believed that Exhausted T cells lack the function of secreting inflammatory, anti-inflammatory, and cytotoxic effector molecules.(96) However, Denis et al.”
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Authors: Goronzy, J. J., & Weyand, C. M.
Affiliations: VA Palo Alto Health Care System (US)
Corresponding author: Goronzy, Jörg J.
ORCID: Goronzy, Jörg J.
Weyand, Cornelia M.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2019-06-11
Volume: 19
Issue: 9
Pages: 573-583
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/s41577-019-0180-1
PMC: PMC7584388
OpenAlex: W2950578975
Cited by: 506
References: 149
Citations by year: 2026: 90 · 2025: 80 · 2024: 90 · 2023: 76 · 2022: 71 · 2021: 62 · 2020: 32 · 2019: 5
FWCI: 3.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX001669)
National Institute on Aging (R01AG045779)
National Heart, Lung, and Blood Institute (P01HL129941, R01HL142068, R01HL117913)
National Institute of Allergy and Infectious Diseases (R01AI108906, R01AI129191, R01AI108891, U19AI057266)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords: cellular senescence, T cell quiescence, T cell self-renewal, T cell differentiation, immunosenescence, anti-aging interventions
MeSH terms: Immunosenescence, Cell Differentiation, Homeostasis, Humans, Immunologic Memory, Receptors, Antigen, T-Cell, T-Lymphocytes, Cellular Senescence

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