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      Circulating Biomarkers of Accelerated Sarcopenia in Respiratory Diseases

      research-article
      1 , * , 1 , 2 , 3 , 4
      Biology
      MDPI
      sarcopenia, Dkk-3, CAF22, miRs, COPD, asthma, tuberculosis

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          Abstract

          Simple Summary

          As we grow older, our muscles become smaller and weaker, a condition called sarcopenia. Several lung diseases can further worsen sarcopenia. Among them, COPD, asthma and tuberculosis are well-recognized causes of muscle loss. However, it is difficult and time-consuming to assess muscle health in elderly people with lung diseases. Here, we aimed to overcome this problem by measuring the blood levels of specific molecules that are related to muscle size and strength. We first show that elderly people with lung diseases have a greater degree of sarcopenia than healthy people. We then show that the blood levels of certain molecules (Dkk-3, CAF22, microRNAs) have varying degrees of associations with muscle size and strength in these patients. Thus, we propose that these molecules can be useful in assessing muscle health and the physical capacity of the elderly with lung diseases. Our findings have clinical applications since the quality and/or quantity of muscle tissues decide everyday lifestyle in the elderly, such as walking, lifting from chair and going to the bathroom etc.

          Abstract

          Skeletal muscle dysfunction is a critical finding in many respiratory diseases. However, a definitive biomarker to assess muscle decline in respiratory diseases is not known. We analyzed the association of plasma levels of glycoprotein Dickkopf-3 (Dkk-3), c-terminal agrin fragment-22 (CAF22) and microRNAs miR-21, miR-134a, miR-133 and miR-206 with hand-grip strength (HGS) and appendicular skeletal mass index (ASMI) in male, 54–73-year-old patients with chronic obstructive pulmonary diseases (COPD), asthma or pulmonary TB ( n = 83–101/group). Patients with respiratory diseases showed a reduction in HGS and gait speed, while a reduction in ASMI was only found in patients with pulmonary TB. Among the sarcopenia indexes, HGS showed the strongest correlation with plasma CAF22, miR-21 and miR-206 levels while ASMI showed the strongest correlation with Dkk-3 and miR-133 in respiratory diseases. We found a modest-to-significant increase in the plasma markers of inflammation, oxidative stress and muscle damage, which had varying degrees of correlations with Dkk-3, CAF22 and selected micro RNAs (miRs) in respiratory diseases. Taken together, our data show that plasma levels of Dkk-3, CAF22 and selected miRs can be useful tools to assess accelerated sarcopenia phenotype in the elderly with respiratory diseases.

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          Most cited references49

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          World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

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            Sarcopenia: European consensus on definition and diagnosis

            The European Working Group on Sarcopenia in Older People (EWGSOP) developed a practical clinical definition and consensus diagnostic criteria for age-related sarcopenia. EWGSOP included representatives from four participant organisations, i.e. the European Geriatric Medicine Society, the European Society for Clinical Nutrition and Metabolism, the International Association of Gerontology and Geriatrics—European Region and the International Association of Nutrition and Aging. These organisations endorsed the findings in the final document. The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as ‘presarcopenia’, ‘sarcopenia’ and ‘severe sarcopenia’. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.
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              Distribution of miRNA expression across human tissues

              We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).
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                Author and article information

                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                03 October 2020
                October 2020
                : 9
                : 10
                : 322
                Affiliations
                [1 ]Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE; akarim@ 123456sharjah.ac.ae
                [2 ]Department of Physiology and Cell Biology, University of Health Sciences, Lahore 54600, Pakistan
                [3 ]Department of Biochemistry, Gomal Medical College, Dera Ismail Khan 29050, Pakistan; drtahir82@ 123456gmail.com
                [4 ]Department of Cardiology, Al Qassimi Hospital, Sharjah 27272, UAE; islam.shah@ 123456moh.gov.ae
                Author notes
                [* ]Correspondence: rqaisar@ 123456sharjah.ac.ae ; Tel.: +974-06-505-7254; Fax: +9716-5585-879
                Article
                biology-09-00322
                10.3390/biology9100322
                7600620
                33023021
                36724ac5-3cbc-4be4-9e27-b3f3fb16f9ed
                © 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
                : 04 September 2020
                : 01 October 2020
                Categories
                Article

                sarcopenia,dkk-3,caf22,mirs,copd,asthma,tuberculosis
                sarcopenia, dkk-3, caf22, mirs, copd, asthma, tuberculosis

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