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      Regulatory RNAs in immunosenescence

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          Abstract

          Background

          Immunosenescence is a multifactorial stress response to different intrinsic and extrinsic insults that cause immune deterioration and is accompanied by genomic or epigenomic perturbations. It is now widely recognized that genes and proteins contributing in the process of immunosenescence are regulated by various noncoding (nc) RNAs, including microRNAs (miRNAs), long ncRNAs, and circular RNAs.

          Aims

          This review article aimed to evaluate the regulatore RNAs roles in the process of immunosenescence.

          Methods

          We analyzed publications that were focusing on the different roles of regulatory RNAs on the several aspects of immunosenescence.

          Results

          In the immunosenescence setting, ncRNAs have been found to play regulatory roles at both transcriptional and post‐transcriptional levels. These factors cooperate to regulate the initiation of gene expression programs and sustaining the senescence phenotype and proinflammatory responses.

          Conclusion

          Immunosenescence is a complex process with pivotal alterations in immune function occurring with age. The extensive network that drive immunosenescence‐related features are are mainly directed by a variety of regulatory RNAs such as miRNAs, lncRNAs, and circRNAs. Latest findings about regulation of senescence by ncRNAs in the innate and adaptive immune cells as well as their role in the immunosenescence pathways, provide a better understanding of regulatory RNAs function in the process of immunosenescence.

          Highlights

          • The immunosenescence process is strictly controlled by genetic and epigenetic factors

          • Innate and adaptive immune responses are affected by immunosenescence

          • The proteostasis is a major hallmark of aging and cellular senescence

          • The regulatory RNAs are involved in the aging of immune system

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          Most cited references153

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          Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

          MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.
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            Gene regulation by long non-coding RNAs and its biological functions

            Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA and proteins, lncRNAs can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic mRNAs and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that lncRNAs are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.
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              Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

              Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.
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                Author and article information

                Contributors
                ghamartale@sums.ac.ir
                Journal
                Immun Inflamm Dis
                Immun Inflamm Dis
                10.1002/(ISSN)2050-4527
                IID3
                Immunity, Inflammation and Disease
                John Wiley and Sons Inc. (Hoboken )
                2050-4527
                08 March 2024
                March 2024
                : 12
                : 3 ( doiID: 10.1002/iid3.v12.3 )
                : e1209
                Affiliations
                [ 1 ] Department of Immunology, School of Medicine Shiraz University of Medical Sciences Shiraz Iran
                [ 2 ] Autoimmune Diseases Research Center University of Medical Sciences Shiraz Iran
                Author notes
                [*] [* ] Correspondence Atefe Ghamar Talepoor, Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345‐3119, Shiraz, Iran.

                Email: ghamartale@ 123456sums.ac.ir

                Article
                IID31209
                10.1002/iid3.1209
                10921898
                38456619
                cd222c88-0c22-4677-a0aa-f778d6d70c82
                © 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 February 2024
                : 22 October 2023
                : 19 February 2024
                Page count
                Figures: 0, Tables: 0, Pages: 11, Words: 7690
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                March 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.9 mode:remove_FC converted:08.03.2024

                aging,immunosenescence,inflammaging,noncoding rna,regulatory rna

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