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Lookup NU author(s): Dr Ramzi LakhdarORCiD
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© 2018 Lakhdar et al. Purpose: Skeletal muscle wasting is an independent predictor of health-related quality of life and survival in patients with COPD, but the complexity of molecular mechanisms associated with this process has not been fully elucidated. We aimed to determine whether an impaired ability to repair DNA damage contributes to muscle wasting and the accelerated aging phenotype in patients with COPD. Patients and methods: The levels of phosphorylated H2AX (γH2AX), a molecule that promotes DNA repair, were assessed in vastus lateralis biopsies from 10 COPD patients with low fat-free mass index (FFMI; COPDL), 10 with preserved FFMI and 10 age-and gender-matched healthy controls. A panel of selected markers for cellular aging processes (CDKN2A/ p16ink4a, SIRT1, SIRT6, and telomere length) were also assessed. Markers of oxidative stress and cell damage and a panel of pro-inflammatory and anti-inflammatory cytokines were evaluated. Markers of muscle regeneration and apoptosis were also measured. Results: We observed a decrease in γH2AX expression in COPDL, which occurred in association with a tendency to increase in CDKN2A/p16ink4a, and a significant decrease in SIRT1 and SIRT6 protein levels. Cellular damage and muscle inflammatory markers were also increased in COPDL. Conclusion: These data are in keeping with an accelerated aging phenotype as a result of impaired DNA repair and dysregulation of cellular homeostasis in the muscle of COPDL. These data indicate cellular degeneration via stress-induced premature senescence and associated inflammatory responses abetted by the senescence-associated secretory phenotype and reflect an increased expression of markers of oxidative stress and inflammation.
Author(s): Lakhdar R, McGuinness D, Drost EM, Shiels PG, Bastos R, Macnee W, Rabinovich RA
Publication type: Article
Publication status: Published
Journal: International Journal of COPD
Year: 2018
Volume: 13
Pages: 1987-1998
Online publication date: 25/06/2018
Acceptance date: 18/03/2018
ISSN (print): 1176-9106
ISSN (electronic): 1178-2005
Publisher: Dove Medical Press Ltd
URL: https://doi.org/10.2147/COPD.S155952
DOI: 10.2147/COPD.S155952
PubMed id: 29970961
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