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      Systems approaches to investigate the role of NF-κB signaling in aging

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          Abstract

          The nuclear factor-κB (NF-κB) signaling pathway is one of the most well-studied pathways related to inflammation, and its involvement in aging has attracted considerable attention. As aging is a complex phenomenon and is the result of a multi-step process, the involvement of the NF-κB pathway in aging remains unclear. To elucidate the role of NF-κB in the regulation of aging, different systems biology approaches have been employed. A multi-omics data-driven approach can be used to interpret and clarify unknown mechanisms but cannot generate mechanistic regulatory structures alone. In contrast, combining this approach with a mathematical modeling approach can identify the mechanistics of the phenomena of interest. The development of single-cell technologies has also helped clarify the heterogeneity of the NF-κB response and underlying mechanisms. Here, we review advances in the understanding of the regulation of aging by NF-κB by focusing on omics approaches, single-cell analysis, and mathematical modeling of the NF-κB network.

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            An Integrated Encyclopedia of DNA Elements in the Human Genome

            Summary The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure, and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall the project provides new insights into the organization and regulation of our genes and genome, and an expansive resource of functional annotations for biomedical research.
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              Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy

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                Author and article information

                Journal
                Biochem J
                Biochem J
                BCJ
                Biochemical Journal
                Portland Press Ltd.
                0264-6021
                1470-8728
                28 January 2022
                28 January 2022
                : 479
                : 2
                : 161-183
                Affiliations
                [1 ]Laboratory for Cell Systems, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan
                [2 ]Basic Research Development Division, ROHTO Pharmaceutical Co., Ltd., Ikuno-ku, Osaka 544-8666, Japan
                [3 ]Center for Drug Design and Research, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan
                Author notes
                Correspondence: Mariko Okada ( mokada@ 123456protein.osaka-u.ac.jp )
                Author information
                http://orcid.org/0000-0002-6210-8223
                Article
                BCJ-479-161
                10.1042/BCJ20210547
                8883486
                35098992
                324433c8-426c-4daf-9ab6-069b361298bf
                © 2022 The Author(s)

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 9 December 2021
                : 6 January 2022
                : 10 January 2022
                Categories
                Systems Biology & Networks
                Immunology & Inflammation
                Aging
                Omics
                Review Articles

                Biochemistry
                aging,mathematical model,nuclear factor kappa b,systems biology,transcription factors
                Biochemistry
                aging, mathematical model, nuclear factor kappa b, systems biology, transcription factors

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