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      Cellular senescence and kidney aging

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          Abstract

          Life expectancy is increasing worldwide, and by 2050 the proportion of the world’s population over 65 years of age is estimated to surpass 1.5 billion. Kidney aging is associated with molecular and physiological changes that cause a loss of renal function and of regenerative potential. As the aging population grows, it is crucial to understand the mechanisms underlying these changes, as they increase the susceptibility to developing acute kidney injury (AKI) and chronic kidney disease (CKD). Various cellular processes and molecular pathways take part in the complex process of kidney aging. In this review, we will focus on the phenomenon of cellular senescence as one of the involved mechanisms at the crossroad of kidney aging, age-related disease, and CKD. We will highlight experimental and clinical findings about the role of cellular senescence in kidney aging and CKD. In addition, we will review challenges in senescence research and emerging therapeutic aspects. We will highlight the great potential of senolytic strategies for the elimination of harmful senescent cells to promote healthy kidney aging and to avoid age-related disease and CKD. This review aims to give insight into recent discoveries and future developments, providing a comprehensive overview of current knowledge on cellular senescence and anti-senescent therapies in the kidney field.

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          Most cited references170

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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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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              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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                Author and article information

                Contributors
                Role: ConceptualizationRole: Writing—original draft
                Role: Writing—review & editing
                Role: ConceptualizationRole: Writing—review & editing
                Journal
                Clin Sci (Lond)
                Clin Sci (Lond)
                cs
                Clinical Science (London, England : 1979)
                Portland Press Ltd.
                0143-5221
                1470-8736
                December 2023
                21 December 2023
                : 137
                : 24
                : 1805-1821
                Affiliations
                [1 ]Department of Nephrology and Hypertension, Medical School Hannover, Germany
                [2 ]Department of Pediatric Kidney, Liver and Metabolic Diseases, Medical School Hannover, Germany
                [3 ]Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel, Germany
                Author notes
                Correspondence: Roland Schmitt ( schmitt.roland@ 123456mh-hannover.de )
                Author information
                https://orcid.org/0000-0003-4415-8355
                Article
                CS20230140
                10.1042/CS20230140
                10739085
                38126209
                eafcb076-88c2-4d8f-bd74-9ac96ebf650d
                © 2023 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
                : 23 July 2023
                : 22 November 2023
                : 05 December 2023
                Page count
                Pages: 17
                Funding
                Funded by: Deutsche Forschungsgemeinschaft (DFG), DOI 501100001659;
                Award ID: SCHM2146/10-1
                Funded by: Deutsche Forschungsgemeinschaft (DFG), DOI 501100001659;
                Award ID: SCHM 2146/11-1
                Funded by: Deutsche Forschungsgemeinschaft (DFG), DOI 501100001659;
                Award ID: ME3696/5-1
                Funded by: Deutsche Forschungsgemeinschaft (DFG), DOI 501100001659;
                Award ID: ME 3696/3-1
                Funded by: Deutsche Forschungsgemeinschaft (DFG), DOI 501100001659;
                Award ID: ME 3696/3-2
                Categories
                Aging
                Pharmacology & Toxicology
                Cell Cycle, Growth & Proliferation
                Gastrointestinal, Renal & Hepatic Systems
                Review Articles

                Medicine
                aging kidney,cellular senescence,chronic kidney disease,senolysis,senolytic therapy
                Medicine
                aging kidney, cellular senescence, chronic kidney disease, senolysis, senolytic therapy

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