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      Clinical Interventions in Aging (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on prevention and treatment of diseases in people over 65 years of age. Sign up for email alerts here.

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      mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator 1α, tumor necrosis factor-α, and interleukin-6 in paraspinal muscles of patients with lumbar kyphosis: a preliminary study

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          Abstract

          Background

          Kyphosis is a spine deformity that can lead to falls and reduced quality of life. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) regulates mitochondrial biogenesis and is important for proper functioning of skeletal muscle, including the paraspinal muscles, which support and allow movement of the spine. The role of PGC-1α in paraspinal muscles in lumbar kyphosis has not been examined. We also examined the expressions of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6.

          Methods

          We obtained paraspinal muscle specimens from 12 patients who underwent posterior lumbar surgery. RNA was isolated from these samples, and quantitative PCR was performed to compare the expression levels of PGC-1α, TNF-α, and IL-6 mRNA between patients with decreased lumbar lordosis (LL) and normal LL patients.

          Results

          TNF-α and IL-6 mRNA expressions in paraspinal muscles were significantly higher in the decreased LL group than in the normal LL group ( P=0.048 for both). PGC-1α mRNA expression was slightly increased in the decreased LL group, but the difference was not significant. Age was significantly positively correlated with PGC-1α mRNA expression ( P=0.010). PGC-1α mRNA expression was significantly positively correlated with TNF-α mRNA expression ( P=0.022). LL was significantly negatively correlated with PGC-1α, TNF-α, and IL-6 mRNA expressions ( P=0.015, 0.036, and 0.010, respectively).

          Conclusion

          TNF-α and IL-6 mRNA expressions in paraspinal muscles were significantly higher in the decreased LL group than in the normal LL group. LL was significantly negatively correlated with PGC-1α, TNF-α, and IL-6 mRNA expressions. PGC-1α mRNA expression levels in paraspinal muscles may be affected by lumbar kyphosis.

          Most cited references32

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          The role of exercise and PGC1alpha in inflammation and chronic disease.

          Inadequate physical activity is linked to many chronic diseases. But the mechanisms that tie muscle activity to health are unclear. The transcriptional coactivator PGC1alpha has recently been shown to regulate several exercise-associated aspects of muscle function. We propose that this protein controls muscle plasticity, suppresses a broad inflammatory response and mediates the beneficial effects of exercise.
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            IL-6-induced skeletal muscle atrophy.

            Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (-17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (-60%) and STAT5 (-33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.
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              Endurance Exercise as a Countermeasure for Aging

              OBJECTIVE— We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity. RESEARCH DESIGN AND METHODS— Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18–30 years old) and older (59–76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot. RESULTS— Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals. CONCLUSIONS— The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.
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                Author and article information

                Journal
                Clin Interv Aging
                Clin Interv Aging
                Clinical Interventions in Aging
                Clinical Interventions in Aging
                Dove Medical Press
                1176-9092
                1178-1998
                2018
                07 September 2018
                : 13
                : 1633-1638
                Affiliations
                Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan, dkudo@ 123456doc.med.akita-u.ac.jp
                Author notes
                Correspondence: Daisuke Kudo, Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan, Tel +81 18 884 6148, Fax +81 18 836 2617, Email dkudo@ 123456doc.med.akita-u.ac.jp
                Article
                cia-13-1633
                10.2147/CIA.S172952
                6135076
                30233161
                98a6d23c-b115-4aa9-aa29-dd921abf25d0
                © 2018 Kudo et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
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                Original Research

                Health & Social care
                aging,pgc-1α,tnf-α,il-6,lumbar kyphosis
                Health & Social care
                aging, pgc-1α, tnf-α, il-6, lumbar kyphosis

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