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      Oxidative Stress, Telomere Shortening, and Apoptosis Associated to Sarcopenia and Frailty in Patients with Multimorbidity

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          Abstract

          Background: The presence of oxidative stress, telomere shortening, and apoptosis in polypathological patients (PP) with sarcopenia and frailty remains unknown. Methods: Multicentric prospective observational study in order to assess oxidative stress markers (catalase, glutathione reductase (GR), total antioxidant capacity to reactive oxygen species (TAC-ROS), and superoxide dismutase (SOD)), absolute telomere length (aTL), and apoptosis (DNA fragmentation) in peripheral blood samples of a hospital-based population of PP. Associations of these biomarkers to sarcopenia, frailty, functional status, and 12-month mortality were analyzed. Results: Of the 444 recruited patients, 97 (21.8%), 278 (62.6%), and 80 (18%) were sarcopenic, frail, or both, respectively. Oxidative stress markers (lower TAC-ROS and higher SOD) were significantly enhanced and aTL significantly shortened in patients with sarcopenia, frailty or both syndromes. No evidence of apoptosis was detected in blood leukocytes of any of the patients. Both oxidative stress markers (GR, p = 0.04) and telomere shortening ( p = 0.001) were associated to death risk and to less survival days. Conclusions: Oxidative stress markers and telomere length were enhanced and shortened, respectively, in blood samples of polypathological patients with sarcopenia and/or frailty. Both were associated to decreased survival. They could be useful in the clinical practice to assess vulnerable populations with multimorbidity and of potential interest as therapeutic targets.

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          Oxidative stress shortens telomeres.

          Telomeres in most human cells shorten with each round of DNA replication, because they lack the enzyme telomerase. This is not, however, the only determinant of the rate of loss of telomeric DNA. Oxidative damage is repaired less well in telomeric DNA than elsewhere in the chromosome, and oxidative stress accelerates telomere loss, whereas antioxidants decelerate it. I suggest here that oxidative stress is an important modulator of telomere loss and that telomere-driven replicative senescence is primarily a stress response. This might have evolved to block the growth of cells that have been exposed to a high risk of mutation.
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            Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials.

            Sarcopenia, the age-related loss of muscle mass and function, imposes a dramatic burden on individuals and society. The development of preventive and therapeutic strategies against sarcopenia is therefore perceived as an urgent need by health professionals and has instigated intensive research on the pathophysiology of this syndrome. The pathogenesis of sarcopenia is multifaceted and encompasses lifestyle habits, systemic factors (e.g., chronic inflammation and hormonal alterations), local environment perturbations (e.g., vascular dysfunction), and intramuscular specific processes. In this scenario, derangements in skeletal myocyte mitochondrial function are recognized as major factors contributing to the age-dependent muscle degeneration. In this review, we summarize prominent findings and controversial issues on the contribution of specific mitochondrial processes - including oxidative stress, quality control mechanisms and apoptotic signaling - on the development of sarcopenia. Extramuscular alterations accompanying the aging process with a potential impact on myocyte mitochondrial function are also discussed. We conclude with presenting methodological and safety considerations for the design of clinical trials targeting mitochondrial dysfunction to treat sarcopenia. Special emphasis is placed on the importance of monitoring the effects of an intervention on muscle mitochondrial function and identifying the optimal target population for the trial. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Aging and Multimorbidity: New Tasks, Priorities, and Frontiers for Integrated Gerontological and Clinical Research.

              Aging is characterized by rising susceptibility to development of multiple chronic diseases and, therefore, represents the major risk factor for multimorbidity. From a gerontological perspective, the progressive accumulation of multiple diseases, which significantly accelerates at older ages, is a milestone for progressive loss of resilience and age-related multisystem homeostatic dysregulation. Because it is most likely that the same mechanisms that drive aging also drive multiple age-related chronic diseases, addressing those mechanisms may reduce the development of multimorbidity. According to this vision, studying multimorbidity may help to understand the biology of aging and, at the same time, understanding the underpinnings of aging may help to develop strategies to prevent or delay the burden of multimorbidity. As a consequence, we believe that it is time to build connections and dialogue between the clinical experience of general practitioners and geriatricians and the scientists who study aging, so as to stimulate innovative research projects to improve the management and the treatment of older patients with multiple morbidities.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                18 August 2020
                August 2020
                : 9
                : 8
                : 2669
                Affiliations
                [1 ]Internal Medicine Department, Hospital Universitario Virgen del Rocío, 41013 Sevilla, Spain; aglezmolina@ 123456gmail.com (Á.G.-M.); m.ollero.baturone@ 123456gmail.com (M.O.-B.)
                [2 ]General and Multiple Use Laboratory, Instituto de Biomedicina de Sevilla, 41013 Sevilla, Spain; rgomez-ibis@ 123456us.es
                [3 ]Internal Medicine Department, Hospital San Juan de Dios del Aljarafe, 41930 Sevilla, Spain; sofiavidalserrano@ 123456gmail.com
                [4 ]Internal Medicine Department, Hospital Royo Villanova, 50015 Zaragoza, Spain; jdiez@ 123456aragon.es
                [5 ]Internal Medicine Department, Hospital Regional, 29010 Málaga, Spain; fersalord@ 123456gmail.com
                [6 ]Internal Medicine Department, Hospital Juan Ramón Jiménez, 21005 Huelva, Spain; msoto@ 123456hotmail.com
                Author notes
                [* ]Correspondence: wittel@ 123456cica.es ; Tel./Fax: +34-(95)5012270
                [†]

                All researchers from the PROTEO project listed at Acknowledgments.

                Author information
                https://orcid.org/0000-0003-4574-4110
                https://orcid.org/0000-0002-3755-6841
                https://orcid.org/0000-0002-3132-2171
                Article
                jcm-09-02669
                10.3390/jcm9082669
                7464426
                32824789
                27f0bef0-842a-44df-9c87-245420975eb0
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 August 2020
                : 14 August 2020
                Categories
                Article

                multimorbidity,polypathological patients,sarcopenia,frailty,oxidative stress,telomere length,apoptosis

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