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      Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience

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          Abstract

          The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-κB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated immunosenescence. Despite recent progress in understanding, the harmonious theory of immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article.

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          Most cited references115

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            The senescence-associated secretory phenotype: the dark side of tumor suppression.

            Cellular senescence is a tumor-suppressive mechanism that permanently arrests cells at risk for malignant transformation. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into proinflammatory cells that have the ability to promote tumor progression.
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              Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.

              The presence of DNA in the cytoplasm of mammalian cells is a danger signal that triggers host immune responses such as the production of type I interferons. Cytosolic DNA induces interferons through the production of cyclic guanosine monophosphate-adenosine monophosphate (cyclic GMP-AMP, or cGAMP), which binds to and activates the adaptor protein STING. Through biochemical fractionation and quantitative mass spectrometry, we identified a cGAMP synthase (cGAS), which belongs to the nucleotidyltransferase family. Overexpression of cGAS activated the transcription factor IRF3 and induced interferon-β in a STING-dependent manner. Knockdown of cGAS inhibited IRF3 activation and interferon-β induction by DNA transfection or DNA virus infection. cGAS bound to DNA in the cytoplasm and catalyzed cGAMP synthesis. These results indicate that cGAS is a cytosolic DNA sensor that induces interferons by producing the second messenger cGAMP.
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                Author and article information

                Journal
                Aging Dis
                Aging Dis
                Aging and Disease
                JKL International LLC
                2152-5250
                December 2020
                1 December 2020
                : 11
                : 6
                : 1363-1373
                Affiliations
                [1-ad-11-6-1363] 1Institute of Biology of FRC of Komi Scientific Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, 167982, Russia.
                [2-ad-11-6-1363] 2Vetek (Seniority), The Movement for Longevity and Quality of Life, Israel.
                [3-ad-11-6-1363] 3Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy
                Author notes
                [* ]Correspondence should be addressed to: Dr. Alexey Moskalev, Institute of Biology of FRC of Komi Scientific Center of Ural Branch of Russian Academy of Sciences, Russia. Email: amoskalev@ 123456list.ru ; Dr. Ilia Stambler, The Movement for Longevity and Quality of Life, Israel. Email: ilia.stambler@ 123456gmail.com ; Dr. Calogero Caruso, University of Palermo, Palermo, Italy. Email: calogero.caruso@ 123456unipa.it.
                Article
                ad-11-6-1363
                10.14336/AD.2020.0603
                7673842
                33269094
                db2178bd-7491-4540-905f-c5d463231dc9
                copyright: © 2020 Moskalev et al.

                this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 4 May 2020
                : 1 June 2020
                : 3 June 2020
                Categories
                Opinion Article

                innate immunity,adaptive immunity,aging,longevity,resilience

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