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      SIRT1 and FOXO1 mRNA expression in PBMC correlates to physical activity in COPD patients

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          Physical activity (PA) is considered as one of the most important prognostic predictors in chronic obstructive pulmonary disease (COPD) patients. Longevity gene, SIRT1, is reported to be involved in the pathogenesis of COPD by regulating the signaling pathways of oxidative stress, inflammation, and aging. We hypothesize that SIRT1 and related genes are also associated with the benefits of PA in COPD patients.


          Eighteen COPD outpatients were enrolled in this study, and their PA level was assessed with an accelerometer. We assessed the SIRT1 and related genes mRNA expression levels in the peripheral blood mononuclear cells (PBMCs) of the subjects. We carried out respiratory function testing, blood gas analysis, the 6-minute walk test, and measurement of the cross-sectional area of the erector spinae muscles (ESMCSA) by chest computed tomography. We analyzed the association of PA with the results of each of the examinations.


          The mean age was 72±9 years, and the mean forced expiratory volume in 1 second was 1.4±0.56 L (52%±19% predicted). Our findings revealed a correlation between the daily PA and ESMCSA. The SIRT1 and Forkhead box O (FOXO)1 mRNA expression levels in PBMCs were positively correlated with moderate-PA time ( r=0.60, p=0.008 for SIRT1 and r=0.59, p=0.01 for FOXO1).

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          Most cited references 25

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          Chronic obstructive pulmonary disease

          Summary Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.
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            Daily activity energy expenditure and mortality among older adults.

            Exercise is associated with mortality benefits but simply expending energy through any activity in an individual's free-living environment may confer survival advantages. To determine whether free-living activity energy expenditure is associated with all-cause mortality among older adults. Free-living activity energy expenditure was assessed in 302 high-functioning, community-dwelling older adults (aged 70-82 years). Total energy expenditure was assessed over 2 weeks using doubly labeled water. Resting metabolic rate was measured using indirect calorimetry and the thermic effect of meals was estimated at 10% of total energy expenditure. Free-living activity energy expenditure was calculated as: (total energy expenditure x 0.90) - resting metabolic rate. Participants were followed up over a mean of 6.15 years (1998-2006). Free-living activity energy expenditure (3 tertiles: low, 770 kcal/d) and all-cause mortality. Fifty-five participants (18.2%) died during follow-up. As a continuous risk factor, an SD increase in free-living activity energy expenditure (287 kcal/d) was associated with a 32% lower risk of mortality after adjusting for age, sex, race, study site, weight, height, percentage of body fat, and sleep duration (hazard ratio, 0.68; 95% confidence interval, 0.48-0.96). Using the same adjustments, individuals in the highest tertile of free-living activity energy expenditure were at a significantly lower mortality risk compared with the lowest tertile (hazard ratio, 0.31; 95% confidence interval, 0.14-0.69). Absolute risk of death was 12.1% in the highest tertile of activity energy expenditure vs 24.7% in the lowest tertile; absolute risks were similar to these for tertiles of physical activity level. The effect of free-living activity energy expenditure changed little after further adjustment for self-rated health, education, prevalent health conditions, and smoking behavior. According to self-reports, individuals expending higher levels of free-living activity energy were more likely to work for pay (P = .004) and climb stairs (P = .01) but self-reported high-intensity exercise, walking for exercise, walking other than for exercise, volunteering, and caregiving did not differ significantly across the activity energy expenditure tertiles. Objectively measured free-living activity energy expenditure was strongly associated with lower risk of mortality in healthy older adults. Simply expending energy through any activity may influence survival in older adults.
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              SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease.

              Abnormal inflammation and accelerated decline in lung function occur in patients with chronic obstructive pulmonary disease (COPD). Human sirtuin (SIRT1), an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. To determine the expression of SIRT1 in lungs of smokers and patients with COPD, and to elucidate the regulation of SIRT1 in response to cigarette smoke in macrophages, and its impact on nuclear factor (NF)-kappaB regulation. SIRT1 and NF-kappaB levels were assessed in lung samples of nonsmokers, smokers, and patients with COPD. Human monocyte-macrophage cells (MonoMac6) were treated with cigarette smoke extract (CSE) to determine the mechanism of CSE-mediated regulation of SIRT1 and its involvement in RelA/p65 regulation and IL-8 release. Peripheral lungs of smokers and patients with COPD showed decreased levels of nuclear SIRT1, as compared with nonsmokers, associated with its post-translational modifications (formation of nitrotyrosine and aldehyde carbonyl adducts). Treatment of MonoMac6 cells with CSE showed decreased levels of SIRT1 associated with increased acetylation of RelA/p65 NF-kappaB. Mutation or knockdown of SIRT1 resulted in increased acetylation of nuclear RelA/p65 and IL-8 release, whereas overexpression of SIRT1 decreased IL-8 release in response to CSE treatment in MonoMac6 cells. SIRT1 levels were reduced in macrophages and lungs of smokers and patients with COPD due to its post-translational modifications by cigarette smoke-derived reactive components, leading to increased acetylation of RelA/p65. Thus, SIRT1 plays a pivotal role in regulation of NF-kappaB-dependent proinflammatory mediators in lungs of smokers and patients with COPD.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                03 November 2017
                : 12
                : 3237-3244
                First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Sugitani, Toyama, Toyama, Japan
                Author notes
                Correspondence: Ryuji Hayashi, First Department of Internal Medicine, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan, Tel +81 76 434 7808, Email hsayaka@
                © 2017 Taka et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( 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.

                Original Research

                Respiratory medicine

                copd, accelerometer, mrna, walking, sedentary, moderate


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