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Review

Accelerated lung aging and chronic obstructive pulmonary disease

, &
Pages 369-380 | Received 18 Nov 2018, Accepted 06 Feb 2019, Published online: 21 Feb 2019

References

  • Foreman KJ, Marquez N, Dolgert A, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018;392(10159):2052–2090.
  • Chapman KR, Mannino DM, Soriano JB, et al. Epidemiology and costs of chronic obstructive pulmonary disease. Eur Respir J. 2006;27(1):188–207.
  • Division. UNDoEaSAP. World population prospects: the 2017 revision, key findings and advance tables. New York (NY): United Nations; 2017. ( Working Paper No. ESA/P/WP/248 ed).
  • Ito K, Barnes PJ. COPD as a disease of accelerated lung aging. Chest. 2009;135(1):173–180.
  • Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013;153(6):1194–1217.
  • Barnes PJ. Senescence in COPD and its comorbidities. Annu Rev Physiol. 2017;79:517–539.
  • Brandsma CA, de Vries M, Costa R, et al. Lung ageing and COPD: is there a role for ageing in abnormal tissue repair? Eur Respir Rev. 2017;26(146):170073.
  • Kukrety SP, Parekh JD, Bailey KL. Chronic obstructive pulmonary disease and the hallmarks of aging. Lung India. 2018;35(4):321–327.
  • Lee J, Sandford A, Man P, et al. Is the aging process accelerated in chronic obstructive pulmonary disease? Curr Opin Pulm Med. 2011;17(2):90–97.
  • MacNee W. Is chronic obstructive pulmonary disease an accelerated aging disease? Ann Am Thorac Soc. 2016;13(Suppl 5):S429–S437.
  • de Vries M, Faiz A, Woldhuis RR, et al. Lung tissue gene-expression signature for the ageing lung in COPD. Thorax. 2017;73(7):609–617.
  • Blackburn EH, Epel ES, Lin J. Human telomere biology: a contributory and interactive factor in aging, disease risks, and protection. Science. 2015;350(6265):1193–1198.
  • Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007;3(10):640–649.
  • Ju Z, Lenhard Rudolph K. Telomere dysfunction and stem cell ageing. Biochimie. 2008;90(1):24–32.
  • Fumagalli M, Rossiello F, Clerici M, et al. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol. 2012;14(4):355–365.
  • Albrecht E, Sillanpaa E, Karrasch S, et al. Telomere length in circulating leukocytes is associated with lung function and disease. Eur Respir J. 2014;43(4):983–992.
  • Rode L, Bojesen SE, Weischer M, et al. Short telomere length, lung function and chronic obstructive pulmonary disease in 46,396 individuals. Thorax. 2013;68(5):429–435.
  • Cordoba-Lanus E, Cabrera-Lopez C, Cazorla-Rivero S, et al. Shorter telomeres in non-smoking patients with airflow limitation. Respir Med. 2018;138:123–128.
  • Mui TS, Man JM, McElhaney JE, et al. Telomere length and chronic obstructive pulmonary disease: evidence of accelerated aging. J Am Geriatr Soc. 2009;57(12):2372–2374.
  • Morla M, Busquets X, Pons J, et al. Telomere shortening in smokers with and without COPD. Eur Respir J. 2006;27(3):525–528.
  • Valdes AM, Andrew T, Gardner JP, et al. Obesity, cigarette smoking, and telomere length in women. Lancet. 2005;366(9486):662–664.
  • Lee J, Sandford AJ, Connett JE, et al. The relationship between telomere length and mortality in chronic obstructive pulmonary disease (COPD). PLoS One. 2012;7(4):e35567.
  • Savale L, Chaouat A, Bastuji-Garin S, et al. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;179(7):566–571.
  • Cordoba-Lanus E, Cazorla-Rivero S, Espinoza-Jimenez A, et al. Telomere shortening and accelerated aging in COPD: findings from the BODE cohort. Respir Res. 2017;18(1):59.
  • Andujar P, Courbon D, Bizard E, et al. Smoking, telomere length and lung function decline: a longitudinal population-based study. Thorax. 2018;73(3):283–285.
  • Tsuji T, Aoshiba K, Nagai A. Alveolar cell senescence in patients with pulmonary emphysema. Am J Respir Crit Care Med. 2006;174(8):886–893.
  • Amsellem V, Gary-Bobo G, Marcos E, et al. Telomere dysfunction causes sustained inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011;184(12):1358–1366.
  • Ahmad T, Sundar IK, Tormos AM, et al. Shelterin telomere protection protein 1 reduction causes telomere attrition and cellular senescence via sirtuin 1 deacetylase in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2017;56(1):38–49.
  • Chen R, Zhang K, Chen H, et al. Telomerase deficiency causes alveolar stem cell senescence-associated low-grade inflammation in lungs. J Biol Chem. 2015;290(52):30813–30829.
  • Stanley SE, Chen JJ, Podlevsky JD, et al. Telomerase mutations in smokers with severe emphysema. J Clin Invest. 2015;125(2):563–570.
  • Birch J, Anderson RK, Correia-Melo C, et al. DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol. 2015;309(10):L1124–L1137.
  • Sen P, Shah PP, Nativio R, et al. Epigenetic mechanisms of longevity and aging. Cell. 2016;166(4):822–839.
  • McCauley BS, Dang W. Histone methylation and aging: lessons learned from model systems. Biochim Biophys Acta. 2014;1839(12):1454–1462.
  • Field AE, Robertson NA, Wang T, et al. DNA methylation clocks in aging: categories, causes, and consequences. Mol Cell. 2018;71(6):882–895.
  • Arancio W, Pizzolanti G, Genovese SI, et al. Epigenetic involvement in Hutchinson-Gilford progeria syndrome: a mini-review. Gerontology. 2014;60(3):197–203.
  • Cheung P, Vallania F, Warsinske HC, et al. Single-cell chromatin modification profiling reveals increased epigenetic variations with aging. Cell. 2018;173(6):1385–1397 e14.
  • Schamberger AC, Mise N, Meiners S, et al. Epigenetic mechanisms in COPD: implications for pathogenesis and drug discovery. Expert Opin Drug Discov. 2014;9(6):609–628.
  • Sood A, Petersen H, Blanchette CM, et al. Wood smoke exposure and gene promoter methylation are associated with increased risk for COPD in smokers. Am J Respir Crit Care Med. 2010;182(9):1098–1104.
  • Wan ES, Qiu W, Baccarelli A, et al. Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome. Hum Mol Genet. 2012;21(13):3073–3082.
  • Qiu W, Baccarelli A, Carey VJ, et al. Variable DNA methylation is associated with chronic obstructive pulmonary disease and lung function. Am J Respir Crit Care Med. 2012;185(4):373–381.
  • Vucic EA, Chari R, Thu KL, et al. DNA methylation is globally disrupted and associated with expression changes in chronic obstructive pulmonary disease small airways. Am J Respir Cell Mol Biol. 2014;50(5):912–922.
  • Carmona JJ, Barfield RT, Panni T, et al. Metastable DNA methylation sites associated with longitudinal lung function decline and aging in humans: an epigenome-wide study in the NAS and KORA cohorts. Epigenetics. 2018;13(10–11):1039–1055.
  • Ito K, Ito M, Elliott WM, et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med. 2005;352(19):1967–1976.
  • Hodge G, Jersmann H, Tran HB, et al. Lymphocyte senescence in COPD is associated with decreased histone deacetylase 2 expression by pro-inflammatory lymphocytes. Respir Res. 2015;16:130.
  • Mercado N, Thimmulappa R, Thomas CM, et al. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress. Biochem Biophys Res Commun. 2011;406(2):292–298.
  • Guarente L. Sirtuins, aging, and metabolism. Cold Spring Harb Symp Quant Biol. 2011;76:81–90.
  • Yao H, Chung S, Hwang JW, et al. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest. 2012;122(6):2032–2045.
  • Rajendrasozhan S, Yang SR, Kinnula VL, et al. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;177(8):861–870.
  • Di Vincenzo S, Heijink IH, Noordhoek JA, et al. SIRT1/FoxO3 axis alteration leads to aberrant immune responses in bronchial epithelial cells. J Cell Mol Med. 2018;22(4):2272–2282.
  • Takasaka N, Araya J, Hara H, et al. Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence. J Immunol. 2014;192(3):958–968.
  • Baker JR, Vuppusetty C, Colley T, et al. MicroRNA-570 is a novel regulator of cellular senescence and inflammaging. FASEB J. 2018; Aug 29:fj201800965R.
  • Baker JR, Vuppusetty C, Colley T, et al. Oxidative stress dependent microRNA-34a activation via PI3Kalpha reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells. Sci Rep. 2016;6:35871.
  • Gu C, Li Y, Liu J, et al. LncRNAmediated SIRT1/FoxO3a and SIRT1/p53 signaling pathways regulate type II alveolar epithelial cell senescence in patients with chronic obstructive pulmonary disease. Mol Med Rep. 2017;15(5):3129–3134.
  • Powers ET, Morimoto RI, Dillin A, et al. Biological and chemical approaches to diseases of proteostasis deficiency. Annu Rev Biochem. 2009;78:959–991.
  • Charmpilas N, Kyriakakis E, Tavernarakis N. Small heat shock proteins in ageing and age-related diseases. Cell Stress Chaperones. 2017;22(4):481–492.
  • Min JN, Whaley RA, Sharpless NE, et al. CHIP deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol Cell Biol. 2008;28(12):4018–4025.
  • Somborac-Bacura A, van der Toorn M, Franciosi L, et al. Cigarette smoke induces endoplasmic reticulum stress response and proteasomal dysfunction in human alveolar epithelial cells. Exp Physiol. 2013;98(1):316–325.
  • Weidner J, Jarenback L, Aberg I, et al. Endoplasmic reticulum, golgi, and lysosomes are disorganized in lung fibroblasts from chronic obstructive pulmonary disease patients. Physiol Rep. 2018;6(5):e13584.
  • Min T, Bodas M, Mazur S, et al. Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema. J Mol Med. 2011;89(6):577–593.
  • Tan SX, Jiang DX, Hu RC, et al. Endoplasmic reticulum stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by cigarette smoke extract. Cell Physiol Biochem. 2017;43(4):1337–1345.
  • Wang Y, Wu ZZ, Wang W. Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema. Oncotarget. 2017;8(44):77685–77695.
  • Yamada Y, Tomaru U, Ishizu A, et al. Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice. Lab Invest. 2015;95(6):625–634.
  • Kuwano K, Araya J, Hara H, et al. Cellular senescence and autophagy in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Respir Invest. 2016;54(6):397–406.
  • Monick MM, Powers LS, Walters K, et al. Identification of an autophagy defect in smokers’ alveolar macrophages. J Immunol. 2010;185(9):5425–5435.
  • Fujii S, Hara H, Araya J, et al. Insufficient autophagy promotes bronchial epithelial cell senescence in chronic obstructive pulmonary disease. Oncoimmunology. 2012;1(5):630–641.
  • Tai H, Wang Z, Gong H, et al. Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence. Autophagy. 2017;13(1):99–113.
  • Vij N, Chandramani-Shivalingappa P, Van Westphal C, et al. Cigarette smoke-induced autophagy impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis. Am J Physiol Cell Physiol. 2018;314(1):C73–C87.
  • Chen ZH, Lam HC, Jin Y, et al. Autophagy protein microtubule-associated protein 1 light chain-3B (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema. Proc Natl Acad Sci USA. 2010;107(44):18880–18885.
  • Bodas M, Patel N, Silverberg D, et al. Master autophagy regulator transcription factor EB regulates cigarette smoke-induced autophagy impairment and chronic obstructive pulmonary disease-emphysema pathogenesis. Antioxid Redox Signal. 2017;27(3):150–167.
  • Li L, Zhang M, Zhang L, et al. Klotho regulates cigarette smoke-induced autophagy: implication in pathogenesis of COPD. Lung. 2017;195(3):295–301.
  • Bodas M, Vij N. Augmenting autophagy for prognosis based intervention of COPD-pathophysiology. Respir Res. 2017;18(1):83.
  • Lane RK, Hilsabeck T, Rea SL. The role of mitochondrial dysfunction in age-related diseases. Biochim Biophys Acta. 2015;1847(11):1387–1400.
  • Prakash YS, Pabelick CM, Sieck GC. Mitochondrial dysfunction in airway disease. Chest. 2017;152(3):618–626.
  • Liu SF, Kuo HC, Tseng CW, et al. Leukocyte mitochondrial DNA copy number is associated with chronic obstructive pulmonary disease. PLoS One. 2015;10(9):e0138716.
  • Puente-Maestu L, Perez-Parra J, Godoy R, et al. Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients. Eur Respir J. 2009;33(5):1045–1052.
  • Leermakers PA, Schols A, Kneppers AEM, et al. Molecular signalling towards mitochondrial breakdown is enhanced in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD). Sci Rep. 2018;8(1):15007.
  • Aravamudan B, Thompson M, Sieck GC, et al. Functional effects of cigarette smoke-induced changes in airway smooth muscle mitochondrial morphology. J Cell Physiol. 2017;232(5):1053–1068.
  • Wiegman CH, Michaeloudes C, Haji G, et al. Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2015;136(3):769–780.
  • Hara H, Araya J, Ito S, et al. Mitochondrial fragmentation in cigarette smoke-induced bronchial epithelial cell senescence. Am J Physiol Lung Cell Mol Physiol. 2013;305(10):L737–L746.
  • Hoffmann RF, Zarrintan S, Brandenburg SM, et al. Prolonged cigarette smoke exposure alters mitochondrial structure and function in airway epithelial cells. Respir Res. 2013;14:97.
  • Ito S, Araya J, Kurita Y, et al. PARK2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis. Autophagy. 2015;11(3):547–559.
  • Araya J, Tsubouchi K, Sato N, et al. PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis. Autophagy. 2018;Oct 5:1–17.
  • Efeyan A, Comb WC, Sabatini DM. Nutrient-sensing mechanisms and pathways. Nature. 2015;517(7534):302–310.
  • Houtkooper RH, Williams RW, Auwerx J. Metabolic networks of longevity. Cell. 2010;142(1):9–14.
  • Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168(6):960–976.
  • Fontana L, Partridge L, Longo VD. Extending healthy life span–from yeast to humans. Science. 2010;328(5976):321–326.
  • Houssaini A, Breau M, Kebe K, et al. mTOR pathway activation drives lung cell senescence and emphysema. JCI Insight. 2018;3(3):e93203.
  • Calhoun C, Shivshankar P, Saker M, et al. Senescent cells contribute to the physiological remodeling of aged lungs. J Gerontol A Biol Sci Med Sci. 2016;71(2):153–160.
  • Yoshida T, Mett I, Bhunia AK, et al. Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema. Nat Med. 2010;16(7):767–773.
  • Hegab AE, Ozaki M, Meligy FY, et al. High fat diet activates adult mouse lung stem cells and accelerates several aging-induced effects. Stem Cell Res. 2018;33:25–35.
  • Hashimoto Y, Sugiura H, Togo S, et al. 27-Hydroxycholesterol accelerates cellular senescence in human lung resident cells. Am J Physiol Lung Cell Mol Physiol. 2016;310(11):L1028–L1041.
  • Cheng XY, Li YY, Huang C, et al. AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema. Oncotarget. 2017;8(14):22513–22523.
  • Hwang JW, Rajendrasozhan S, Yao H, et al. FOXO3 deficiency leads to increased susceptibility to cigarette smoke-induced inflammation, airspace enlargement, and chronic obstructive pulmonary disease. J Immunol. 2011;187(2):987–998.
  • He S, Sharpless NE. Senescence in health and disease. Cell. 2017;169(6):1000–1011.
  • Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965;37:614–636.
  • Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130(2):223–233.
  • Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013;75:685–705.
  • Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120(4):513–522.
  • Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016;530(7589):184–189.
  • Aoshiba K, Zhou F, Tsuji T, et al. DNA damage as a molecular link in the pathogenesis of COPD in smokers. Eur Respir J. 2012;39(6):1368–1376.
  • Muller KC, Welker L, Paasch K, et al. Lung fibroblasts from patients with emphysema show markers of senescence in vitro. Respir Res. 2006;7:32.
  • Barnes PJ. Mediators of chronic obstructive pulmonary disease. Pharmacol Rev. 2004;56(4):515–548.
  • Tsuji T, Aoshiba K, Nagai A. Cigarette smoke induces senescence in alveolar epithelial cells. Am J Respir Cell Mol Biol. 2004;31(6):643–649.
  • Noureddine H, Gary-Bobo G, Alifano M, et al. Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for pulmonary hypertension in chronic lung disease. Circ Res. 2011;109(5):543–553.
  • Hashimoto M, Asai A, Kawagishi H, et al. Elimination of p19(ARF)-expressing cells enhances pulmonary function in mice. JCI Insight. 2016;1(12):e87732.
  • John-Schuster G, Gunter S, Hager K, et al. Inflammaging increases susceptibility to cigarette smoke-induced COPD. Oncotarget. 2016;7(21):30068–30083.
  • Rashid K, Sundar IK, Gerloff J, et al. Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema. Sci Rep. 2018;8(1):9023.
  • Oh J, Lee YD, Wagers AJ. Stem cell aging: mechanisms, regulators and therapeutic opportunities. Nat Med. 2014;20(8):870–880.
  • Rock JR, Randell SH, Hogan BL. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling. Dis model Mech. 2010;3(9–10):545–556.
  • Barkauskas CE, Cronce MJ, Rackley CR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest. 2013;123(7):3025–3036.
  • Chen Q, Suresh Kumar V, Finn J, et al. CD44(high) alveolar type II cells show stem cell properties during steady-state alveolar homeostasis. Am J Physiol Lung Cell Mol Physiol. 2017;313(1):L41–L51.
  • Fujino N, Kubo H, Suzuki T, et al. Isolation of alveolar epithelial type II progenitor cells from adult human lungs. Lab Invest. 2011;91(3):363–378.
  • Ghosh M, Miller YE, Nakachi I, et al. Exhaustion of airway basal progenitor cells in early and established chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2018;197(7):885–896.
  • Staudt MR, Buro-Auriemma LJ, Walters MS, et al. Airway basal stem/progenitor cells have diminished capacity to regenerate airway epithelium in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;190(8):955–958.
  • Alder JK, Barkauskas CE, Limjunyawong N, et al. Telomere dysfunction causes alveolar stem cell failure. Proc Natl Acad Sci USA. 2015;112(16):5099–5104.
  • Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005;33(2):145–152.
  • Tura-Ceide O, Lobo B, Paul T, et al. Cigarette smoke challenges bone marrow mesenchymal stem cell capacities in guinea pig. Respir Res. 2017;18(1):50.
  • Paschalaki KE, Starke RD, Hu Y, et al. Dysfunction of endothelial progenitor cells from smokers and chronic obstructive pulmonary disease patients due to increased DNA damage and senescence. Stem Cells. 2013;31(12):2813–2826.
  • Palange P, Testa U, Huertas A, et al. Circulating haemopoietic and endothelial progenitor cells are decreased in COPD. Eur Respir J. 2006;27(3):529–541.
  • Fadini GP, Schiavon M, Cantini M, et al. Circulating progenitor cells are reduced in patients with severe lung disease. Stem Cells. 2006;24(7):1806–1813.
  • Franceschi C, Garagnani P, Parini P, et al. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14(10):576–590.
  • Salminen A, Kaarniranta K, Kauppinen A. Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging (Albany NY). 2012;4(3):166–175.
  • Ventura MT, Casciaro M, Gangemi S, et al. Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clin Mol Allergy. 2017;15:21.
  • Conboy IM, Conboy MJ, Wagers AJ, et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433(7027):760–764.
  • Sinden NJ, Stockley RA. Systemic inflammation and comorbidity in COPD: a result of ‘overspill’ of inflammatory mediators from the lungs? Review of the evidence. Thorax. 2010;65(10):930–936.
  • Van Eeden S, Leipsic J, Paul Man SF, et al. The relationship between lung inflammation and cardiovascular disease. Am J Respir Crit Care Med. 2012;186(1):11–16.
  • Shaykhiev R, Crystal RG. Innate immunity and chronic obstructive pulmonary disease: a mini-review. Gerontology. 2013;59(6):481–489.
  • Karayama M, Inui N, Suda T, et al. Antiendothelial cell antibodies in patients with COPD. Chest. 2010;138(6):1303–1308.
  • Dermaku-Sopjani M, Kolgeci S, Abazi S, et al. Significance of the anti-aging protein Klotho. Mol Membr Biol. 2013;30(8):369–385.
  • Gao W, Yuan C, Zhang J, et al. Klotho expression is reduced in COPD airway epithelial cells: effects on inflammation and oxidant injury. Clin Sci (Lond). 2015;129(12):1011–1023.
  • Sato T, Seyama K, Sato Y, et al. Senescence marker protein-30 protects mice lungs from oxidative stress, aging, and smoking. Am J Respir Crit Care Med. 2006;174(5):530–537.
  • Onodera K, Sugiura H, Yamada M, et al. Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease. Thorax. 2017;72(10):893–904.
  • Laucho-Contreras ME, Polverino F, Rojas-Quintero J, et al. Club cell protein 16 (Cc16) deficiency increases inflamm-aging in the lungs of mice. Physiol Rep. 2018;6(15):e13797.
  • Rutten EP, Gopal P, Wouters EF, et al. Various mechanistic pathways representing the aging process are altered in COPD. Chest. 2016;149(1):53–61.
  • Vermeij WP, Hoeijmakers JH, Pothof J. Genome integrity in aging: human syndromes, mouse models, and therapeutic options. Annu Rev Pharmacol Toxicol. 2016;56(1):427–445.
  • Shamanna RA, Croteau DL, Lee JH, et al. Recent advances in understanding Werner syndrome. F1000Res. 2017;6:1779.
  • Ceylan E, Kocyigit A, Gencer M, et al. Increased DNA damage in patients with chronic obstructive pulmonary disease who had once smoked or been exposed to biomass. Respir Med. 2006;100(7):1270–1276.
  • Nyunoya T, Monick MM, Klingelhutz AL, et al. Cigarette smoke induces cellular senescence via Werner’s syndrome protein down-regulation. Am J Respir Crit Care Med. 2009;179(4):279–287.
  • Caramori G, Adcock IM, Casolari P, et al. Unbalanced oxidant-induced DNA damage and repair in COPD: a link towards lung cancer. Thorax. 2011;66(6):521–527.
  • Vanfleteren LE, Spruit MA, Groenen M, et al. Clusters of comorbidities based on validated objective measurements and systemic inflammation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(7):728–735.
  • Taka C, Hayashi R, Shimokawa K, et al. SIRT1 and FOXO1 mRNA expression in PBMC correlates to physical activity in COPD patients. Int J Chron Obstruct Pulmon Dis. 2017;12:3237–3244.
  • Lakhdar R, McGuinness D, Drost EM, et al. Role of accelerated aging in limb muscle wasting of patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:1987–1998.
  • Sugiyama Y, Asai K, Yamada K, et al. Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2017;12:765–772.
  • Tanaka R, Sugiura H, Yamada M, et al. Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2018;13:1333–1342.
  • Yang J, Huang T, Petralia F, et al. Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases. Sci Rep. 2015;5:15145.
  • Newman JC, Milman S, Hashmi SK, et al. Strategies and challenges in clinical trials targeting human aging. J Gerontol A Biol Sci Med Sci. 2016;71(11):1424–1434.
  • Bishwakarma R, Zhang W, Lin YL, et al. Metformin use and health care utilization in patients with coexisting chronic obstructive pulmonary disease and diabetes mellitus. Int J Chron Obstruct Pulmon Dis. 2018;13:793–800.
  • Zhou S, Wright JL, Liu J, et al. Aging does not enhance experimental cigarette smoke-induced COPD in the mouse. PLoS One. 2013;8(8):e71410.

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