The central role of DNA damage in immunosenescence
Ageing is the biggest risk factor for the development of multiple chronic diseases as well as increased infection susceptibility and severity of diseases such as influenza and COVID-19. This increased disease risk is linked to changes in immune function during ageing termed immunosenescence. Age-rel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Aging |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fragi.2023.1202152/full |
| _version_ | 1797789157320294400 |
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| author | Loren Kell Loren Kell Loren Kell Anna Katharina Simon Anna Katharina Simon Ghada Alsaleh Ghada Alsaleh Lynne S. Cox |
| author_facet | Loren Kell Loren Kell Loren Kell Anna Katharina Simon Anna Katharina Simon Ghada Alsaleh Ghada Alsaleh Lynne S. Cox |
| author_sort | Loren Kell |
| collection | DOAJ |
| description | Ageing is the biggest risk factor for the development of multiple chronic diseases as well as increased infection susceptibility and severity of diseases such as influenza and COVID-19. This increased disease risk is linked to changes in immune function during ageing termed immunosenescence. Age-related loss of immune function, particularly in adaptive responses against pathogens and immunosurveillance against cancer, is accompanied by a paradoxical gain of function of some aspects of immunity such as elevated inflammation and increased incidence of autoimmunity. Of the many factors that contribute to immunosenescence, DNA damage is emerging as a key candidate. In this review, we discuss the evidence supporting the hypothesis that DNA damage may be a central driver of immunosenescence through senescence of both immune cells and cells of non-haematopoietic lineages. We explore why DNA damage accumulates during ageing in a major cell type, T cells, and how this may drive age-related immune dysfunction. We further propose that existing immunosenescence interventions may act, at least in part, by mitigating DNA damage and restoring DNA repair processes (which we term “genoprotection”). As such, we propose additional treatments on the basis of their evidence for genoprotection, and further suggest that this approach may provide a viable therapeutic strategy for improving immunity in older people. |
| first_indexed | 2024-03-13T01:46:42Z |
| format | Article |
| id | doaj.art-8b48fdc618c94f10a8bfbc1bff10bed9 |
| institution | Directory Open Access Journal |
| issn | 2673-6217 |
| language | English |
| last_indexed | 2024-03-13T01:46:42Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging |
| spelling | doaj.art-8b48fdc618c94f10a8bfbc1bff10bed92023-07-03T07:19:40ZengFrontiers Media S.A.Frontiers in Aging2673-62172023-07-01410.3389/fragi.2023.12021521202152The central role of DNA damage in immunosenescenceLoren Kell0Loren Kell1Loren Kell2Anna Katharina Simon3Anna Katharina Simon4Ghada Alsaleh5Ghada Alsaleh6Lynne S. Cox7Department of Biochemistry, University of Oxford, Oxford, United KingdomBotnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United KingdomThe Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United KingdomThe Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United KingdomMax Delbrück Center for Molecular Medicine, Berlin, GermanyBotnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United KingdomThe Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomAgeing is the biggest risk factor for the development of multiple chronic diseases as well as increased infection susceptibility and severity of diseases such as influenza and COVID-19. This increased disease risk is linked to changes in immune function during ageing termed immunosenescence. Age-related loss of immune function, particularly in adaptive responses against pathogens and immunosurveillance against cancer, is accompanied by a paradoxical gain of function of some aspects of immunity such as elevated inflammation and increased incidence of autoimmunity. Of the many factors that contribute to immunosenescence, DNA damage is emerging as a key candidate. In this review, we discuss the evidence supporting the hypothesis that DNA damage may be a central driver of immunosenescence through senescence of both immune cells and cells of non-haematopoietic lineages. We explore why DNA damage accumulates during ageing in a major cell type, T cells, and how this may drive age-related immune dysfunction. We further propose that existing immunosenescence interventions may act, at least in part, by mitigating DNA damage and restoring DNA repair processes (which we term “genoprotection”). As such, we propose additional treatments on the basis of their evidence for genoprotection, and further suggest that this approach may provide a viable therapeutic strategy for improving immunity in older people.https://www.frontiersin.org/articles/10.3389/fragi.2023.1202152/fullageingimmunosenescencesenescenceimmunologyDNA repairDNA damage |
| spellingShingle | Loren Kell Loren Kell Loren Kell Anna Katharina Simon Anna Katharina Simon Ghada Alsaleh Ghada Alsaleh Lynne S. Cox The central role of DNA damage in immunosenescence Frontiers in Aging ageing immunosenescence senescence immunology DNA repair DNA damage |
| title | The central role of DNA damage in immunosenescence |
| title_full | The central role of DNA damage in immunosenescence |
| title_fullStr | The central role of DNA damage in immunosenescence |
| title_full_unstemmed | The central role of DNA damage in immunosenescence |
| title_short | The central role of DNA damage in immunosenescence |
| title_sort | central role of dna damage in immunosenescence |
| topic | ageing immunosenescence senescence immunology DNA repair DNA damage |
| url | https://www.frontiersin.org/articles/10.3389/fragi.2023.1202152/full |
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