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      Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers

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          Abstract

          Rationale

          Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear.

          Objectives

          To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DL CO) corrected for alveolar volume (K CO).

          Methods

          Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD).

          Measurements and Main Results

          Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low K CO had lower ASMMI values compared to those with normal K CO. Moreover, female smokers with low K CO, had lower BMD and shorter TL compared to those with normal K CO.

          Conclusions

          Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a K CO decrease. Decreased K CO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.

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          Most cited references19

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          Obesity, cigarette smoking, and telomere length in women.

          Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood cells. We investigated 1122 white women aged 18-76 years and found that telomere length decreased steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our results emphasise the pro-ageing effects of obesity and cigarette smoking.
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            Epidemiology of sarcopenia among the elderly in New Mexico.

            Muscle mass decreases with age, leading to "sarcopenia," or low relative muscle mass, in elderly people. Sarcopenia is believed to be associated with metabolic, physiologic, and functional impairments and disability. Methods of estimating the prevalence of sarcopenia and its associated risks in elderly populations are lacking. Data from a population-based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico (the New Mexico Elder Health Survey, 1993-1995) were analyzed to develop a method for estimating the prevalence of sarcopenia. An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a random subsample (n = 199) of participants and was extended to the total sample. Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 (m2) being less than two standard deviations below the mean of a young reference group. Prevalences increased from 13-24% in persons under 70 years of age to >50% in persons over 80 years of age, and were slightly greater in Hispanics than in non-Hispanic whites. Sarcopenia was significantly associated with self-reported physical disability in both men and women, independent of ethnicity, age, morbidity, obesity, income, and health behaviors. This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia.
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              Alveolar cell senescence in patients with pulmonary emphysema.

              The prevalence of chronic obstructive pulmonary disease (COPD) is age-dependent, suggesting an intimate relationship between the pathogenesis of COPD and aging. In this study we investigated whether the senescence of alveolar epithelial and endothelial cells is accelerated in emphysematous lungs. Samples of lung tissue were obtained from patients with emphysema, asymptomatic smokers, and asymptomatic nonsmokers. Paraffin-embedded lung tissue sections were evaluated for cellular senescence by quantitative fluorescence in situ hybridization to assess telomere shortening, and by immunohistochemistry to assess the expression of senescence-associated cyclin-dependent kinase inhibitors. Tissue sections were also immunostained for proliferating cell nuclear antigen (PCNA), surfactant protein A, and CD31. The patients with emphysema had significantly higher percentages of type II cells positive for p16INK4a and p21CIP1/WAF1/Sdi1 than the asymptomatic smokers and nonsmokers. They had also significantly higher percentages of endothelial cells positive for p16INK4a than the asymptomatic smokers and nonsmokers, and higher percentages of endothelial cells positive for p21CIP1/WAF1/Sdi1 than the asymptomatic nonsmokers. Telomere length in alveolar type II cells and endothelial cells was significantly shorter in the patients with emphysema than in the asymptomatic nonsmokers. The level of p16INK4a expression was negatively correlated with the level of PCNA expression. The level of alveolar cell senescence was positively correlated with airflow limitation. These results suggest that the senescence of alveolar epithelial and endothelial cells is accelerated in patients with emphysema. Cellular senescence may explain the abnormal cell turnover that promotes the loss of alveolar cells in emphysematous lungs.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 March 2015
                2015
                : 10
                : 3
                : e0121539
                Affiliations
                [1 ]APHP, Hôpital Henri Mondor, DHU-ATVB, Département de Physiologie-Explorations Fonctionnelles, F-94010, Créteil, France
                [2 ]INSERM U955 and Université Paris Est (UPEC), UMR U955, Faculté de médecine, F-94010, Créteil, France
                [3 ]Centre Hospitalier Intercommunal, DHU-ATVB, Département de Pneumologie et Pathologie Professionnelle, F-94000, Créteil, France
                [4 ]APHP, Hôpital Henri Mondor, Département de Santé Publique, F-94010, Créteil, France
                [5 ]Université Paris Est (UPEC), Faculté de médecine, LIC, EA4393, F-94010, Créteil, France
                [6 ]INSERM, Centre d’Investigation Clinique 1430, AP-HP, Hôpital Henri Mondor, F-94010, Créteil, France
                [7 ]APHP, Hôpital Henri-Mondor, Département d’Addictologie, F-94010, Créteil, France
                [8 ]APHP, Hôpital Henri Mondor, Plateforme de Ressources Biologiques, F-94010, Créteil, France
                [9 ]APHP, Hôpital Henri Mondor, Département d’Immunologie Biologique, F-94010, Créteil, France
                [10 ]APHP, Hôpital Henri Mondor, DHU-ATVB, Département de Cardiologie, F-94010, Créteil, France
                Helmholtz Zentrum München, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LB CC BM JB SA BH. Performed the experiments: LB LM EM PLC LV LH LF AC PA ZS AL BG SH JD BH. Analyzed the data: LB SB EA. Contributed reagents/materials/analysis tools: EM SH. Wrote the paper: LB CC GD BM JB SA.

                Article
                PONE-D-14-38064
                10.1371/journal.pone.0121539
                4364985
                25785739
                fcc65527-8338-4538-9edb-bcf1bf9d7c82
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 24 August 2014
                : 2 February 2015
                Page count
                Figures: 1, Tables: 5, Pages: 12
                Funding
                This research was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM) grant C09-11. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                The data cannot be made publicly available due to legal and ethical restrictions from the French Commission nationale de l'informatique et des libertés. Data are from the Inserm translationnal C09-11 study. Requests for data use can now be made to the Scientific Manager of the study, Sonia Gueguen, ( sonia.gueguen@ 123456inserm.fr ) or to the corresponding author Dr. Laurent Boyer ( laurent.boyer@ 123456hmn.aphp.fr ).

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