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  1. Article ; Online: Senescent T cells: Beneficial and detrimental roles.

    Laphanuwat, Phatthamon / Gomes, Daniel Claudio Oliveira / Akbar, Arne N

    Immunological reviews

    2023  Volume 316, Issue 1, Page(s) 160–175

    Abstract: As the thymus involutes during aging, the T-cell pool has to be maintained by the periodic expansion of preexisting T cells during adulthood. A conundrum is that repeated episodes of activation and proliferation drive the differentiation of T cells ... ...

    Abstract As the thymus involutes during aging, the T-cell pool has to be maintained by the periodic expansion of preexisting T cells during adulthood. A conundrum is that repeated episodes of activation and proliferation drive the differentiation of T cells toward replicative senescence, due to telomere erosion. This review discusses mechanisms that regulate the end-stage differentiation (senescence) of T cells. Although these cells, within both CD4 and CD8 compartments, lose proliferative activity after antigen-specific challenge, they acquire innate-like immune function. While this may confer broad immune protection during aging, these senescent T cells may also cause immunopathology, especially in the context of excessive inflammation in tissue microenvironments.
    MeSH term(s) Humans ; Adult ; T-Lymphocytes ; Cellular Senescence ; Aging ; Cell Differentiation ; Antigens ; CD8-Positive T-Lymphocytes
    Chemical Substances Antigens
    Language English
    Publishing date 2023-04-25
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.13206
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reply.

    Chambers, Emma S / Akbar, Arne N

    The Journal of allergy and clinical immunology

    2020  Volume 146, Issue 4, Page(s) 922–923

    MeSH term(s) Aging ; Humans ; Inflammation
    Keywords covid19
    Language English
    Publishing date 2020-07-25
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2020.06.020
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  3. Article ; Online: Aging and frailty immune landscape.

    De Maeyer, Roel P H / Akbar, Arne N

    Nature aging

    2021  Volume 2, Issue 4, Page(s) 280–281

    MeSH term(s) Humans ; Frailty ; Aging ; Immunosenescence
    Language English
    Publishing date 2021-11-25
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 2662-8465
    ISSN (online) 2662-8465
    DOI 10.1038/s43587-022-00208-w
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  4. Article ; Online: Induction of T Cell Senescence by Cytokine Induced Bystander Activation.

    Abbas, Attiya A / Akbar, Arne N

    Frontiers in aging

    2021  Volume 2, Page(s) 714239

    Abstract: As people around the world continue to live longer, maintaining a good quality of life is of increasing importance. The COVID-19 pandemic revealed that the elderly are disproportionally vulnerable to infectious diseases and Immunosenescence plays a ... ...

    Abstract As people around the world continue to live longer, maintaining a good quality of life is of increasing importance. The COVID-19 pandemic revealed that the elderly are disproportionally vulnerable to infectious diseases and Immunosenescence plays a critical role in that. An ageing immune system influences the conventional activity of T cells which are at the forefront of eliminating harmful foreign antigens. With ageing, unconventional end-stage T cells, that exhibit a senescent phenotype, amass. These senescent T cells deviate from T cell receptor (TCR) signaling toward natural killer (NK) activity. The transition toward innate immune cell function from these adaptor T cells impacts antigen specificity, contributing to increased susceptibility of infection in the elderly. The mechanism by which senescent T cells arise remains largely unclear however in this review we investigate the part that bystander activation plays in driving the change in function of T cells with age. Cytokine-induced bystander activation may offer a plausible explanation for the induction of NK-like activity and senescence in T cells. Further understanding of these specific NK-like senescent T cells allows us to identify the benefits and detriments of these cells in health and disease which can be utilized or regulated, respectively. This review discusses the dynamic of senescent T cells in adopting NK-like T cells and the implications that has in an infectious disease context, predominately in the elderly.
    Language English
    Publishing date 2021-07-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 3076785-4
    ISSN 2673-6217 ; 2673-6217
    ISSN (online) 2673-6217
    ISSN 2673-6217
    DOI 10.3389/fragi.2021.714239
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  5. Article ; Online: Vitamin D

    Sayegh, Souraya / Fantecelle, Carlos Henrique / Laphanuwat, Phatthamon / Subramanian, Priya / Rustin, Malcom H A / Gomes, Daniel C O / Akbar, Arne N / Chambers, Emma S

    Aging cell

    2024  Volume 23, Issue 4, Page(s) e14093

    Abstract: ... Vitamin ... ...

    Abstract Vitamin D
    MeSH term(s) Adult ; Humans ; Aged ; Cellular Senescence/genetics ; Cholecalciferol/pharmacology ; Cholecalciferol/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; Aging ; Fibroblasts/metabolism ; Inflammation Mediators/metabolism ; Immunity
    Chemical Substances Cholecalciferol (1C6V77QF41) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Inflammation Mediators
    Language English
    Publishing date 2024-01-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 2113083-8
    ISSN 1474-9726 ; 1474-9718
    ISSN (online) 1474-9726
    ISSN 1474-9718
    DOI 10.1111/acel.14093
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  6. Article ; Online: Aging immunity may exacerbate COVID-19.

    Akbar, Arne N / Gilroy, Derek W

    Science (New York, N.Y.)

    2020  Volume 369, Issue 6501, Page(s) 256–257

    MeSH term(s) Age Factors ; Aged ; Aging/immunology ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Cytokines/immunology ; Humans ; Immunosenescence ; Inflammation/immunology ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; SARS-CoV-2 ; T-Lymphocytes/immunology
    Chemical Substances Cytokines
    Keywords covid19
    Language English
    Publishing date 2020-07-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abb0762
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  9. Article ; Online: Can blocking inflammation enhance immunity during aging?

    Chambers, Emma S / Akbar, Arne N

    The Journal of allergy and clinical immunology

    2020  Volume 145, Issue 5, Page(s) 1323–1331

    Abstract: Aging is a global burden, and the increase in life span does not increase in parallel with health span. Therefore, older adults are currently living longer with chronic diseases, increased infections, and cancer. A characteristic of aging is the presence ...

    Abstract Aging is a global burden, and the increase in life span does not increase in parallel with health span. Therefore, older adults are currently living longer with chronic diseases, increased infections, and cancer. A characteristic of aging is the presence of chronic low-grade inflammation that is characterized by elevated concentrations of IL-6, TNF-α, and C-reactive protein, which has been termed inflammaging. Previous studies have demonstrated that chronic inflammation interferes with T-cell response and macrophage function and is also detrimental for vaccine responses. This raises the question of whether therapeutic strategies that reduce inflammation may be useful for improving immunity in older adults. In this review we discuss the potential causes of inflammaging, the cellular source of the inflammatory mediators, and the mechanisms by which inflammation may inhibit immunity. Finally, we describe existing interventions that target inflammation that have been used to enhance immunity during aging.
    MeSH term(s) Aging/immunology ; Animals ; Humans ; Immunity ; Inflammation/drug therapy ; Inflammation/immunology
    Language English
    Publishing date 2020-05-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2020.03.016
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  10. Article ; Online: Targeting Inflammation and Immunosenescence to Improve Vaccine Responses in the Elderly.

    Pereira, Branca / Xu, Xiao-Ning / Akbar, Arne N

    Frontiers in immunology

    2020  Volume 11, Page(s) 583019

    Abstract: One of the most appreciated consequences of immunosenescence is an impaired response to vaccines with advanced age. While most studies report impaired antibody responses in older adults as a correlate of vaccine efficacy, it is now widely appreciated ... ...

    Abstract One of the most appreciated consequences of immunosenescence is an impaired response to vaccines with advanced age. While most studies report impaired antibody responses in older adults as a correlate of vaccine efficacy, it is now widely appreciated that this may fail to identify important changes occurring in the immune system with age that may affect vaccine efficacy. The impact of immunosenescence on vaccination goes beyond the defects on antibody responses as T cell-mediated responses are reshaped during aging and certainly affect vaccination. Likewise, age-related changes in the innate immune system may have important consequences on antigen presentation and priming of adaptive immune responses. Importantly, a low-level chronic inflammatory status known as inflammaging has been shown to inhibit immune responses to vaccination and pharmacological strategies aiming at blocking baseline inflammation can be potentially used to boost vaccine responses. Yet current strategies aiming at improving immunogenicity in the elderly have mainly focused on the use of adjuvants to promote local inflammation. More research is needed to understand the role of inflammation in vaccine responses and to reconcile these seemingly paradoxical observations. Alternative approaches to improve vaccine responses in the elderly include the use of higher vaccine doses or alternative routes of vaccination showing only limited benefits. This review will explore novel targets and potential new strategies for enhancing vaccine responses in older adults, including the use of anti-inflammatory drugs and immunomodulators.
    MeSH term(s) Aged ; Aging/immunology ; B-Lymphocytes/immunology ; Humans ; Immunity, Humoral ; Immunity, Innate ; Immunosenescence/immunology ; Inflammation/immunology ; T-Lymphocytes/immunology ; Treatment Outcome ; Vaccination/methods ; Vaccines/immunology
    Chemical Substances Vaccines
    Keywords covid19
    Language English
    Publishing date 2020-10-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.583019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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