Physical Exercise as an Immunomodulator of Chronic Diseases in Aging

in Journal of Physical Activity and Health
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Background: The progressive dysfunction of the immune system during aging appears to be involved in the pathogenesis of several age-related disorders. However, regular physical exercise can present “antiaging” effects on several physiological systems. Methods: A narrative review of studies investigating the chronic effects of exercise and physical activity on the immune system and its association with age-related chronic diseases was carried out according to the guidelines for writing a narrative review. Results: There is compelling evidence suggesting that age-related immune system alterations play a key role on the pathophysiology of atherosclerosis, hypertension, chronic heart failure, type 2 diabetes, obesity, arthritis, and chronic obstructive pulmonary disease. On the other hand, the regular practice of physical activity appears to improve most of the inflammatory/immunological processes involved in these diseases. Conclusion: Epidemiological, experimental, and clinical studies permit us to affirm that regular physical activity improves immunomodulation and may play a key role in the prevention and treatment of several age-related chronic diseases. However, further studies are needed to better describe the prophylactic and therapeutic effects of physical exercise in specific organs of older individuals, as well as the mechanisms involved in such response.

Ciolac and Rodrigues da Silva are with the Exercise and Chronic Disease Research Laboratory (ECDR) and Post-Graduate Program in Movement Sciences, Department of Physical Education, School of Sciences, São Paulo State University (UNESP), Bauru, Sao Paulo, Brazil. Vieira is with the Post-Graduation Program in Sciences of Human Movement and Reghabilitation, Federal University of São Paulo, Santos, Sao Paulo, Brazil; Post-Graduate Program in Bioengineering and in Biomedical Engineering, Universidade Brasil, Sao Paulo, Brazil; School of Medicine, Anhembi Morumbi University, São José dos Campos, Sao Paulo, Brazil; and Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology, São José dos Campos, Sao Paulo, Brazil.

Ciolac (emmanuel.ciolac@unesp.br) is corresponding author.
  • 1.

    Ciolac EG. Exercise training as a preventive tool for age-related disorders: a brief review. Clinics. 2013;68(5):710717. PubMed ID: 23778419 doi:10.6061/clinics/2013(05)20

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    American College of Sports Medicine, Chodzko-Zajko WJ, Proctor DN, et al. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc. 2009;41(7):15101530. PubMed ID: 19516148 doi:10.1249/MSS.0b013e3181a0c95c

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Cao Dinh H, Beyer I, Mets T, et al. Effects of physical exercise on markers of cellular immunosenescence: a systematic review. Calcif Tissue Int. 2017;100(2):193215. PubMed ID: 27866236 doi:10.1007/s00223-016-0212-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Turner JE. Is immunosenescence influenced by our lifetime “dose” of exercise? Biogerontology. 2016;17(3):581602. PubMed ID: 27023222 doi:10.1007/s10522-016-9642-z

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Panda A, Arjona A, Sapey E, et al. Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol. 2009;30(7):325333. PubMed ID: 19541535 doi:10.1016/j.it.2009.05.004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Geiger H, de Haan G, Florian MC. The ageing haematopoietic stem cell compartment. Nat Rev Immunol. 2013;13(5):376389. PubMed ID: 23584423 doi:10.1038/nri3433

  • 7.

    Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol. 2013;14(5):428436. PubMed ID: 23598398 doi:10.1038/ni.2588

  • 8.

    Pedersen BK. Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease. Eur J Clin Invest. 2017;47(8):600611. PubMed ID: 28722106 doi:10.1111/eci.12781

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nat Rev Rheumatol. 2015;11(2):8697. PubMed ID: 25422002 doi:10.1038/nrrheum.2014.193

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429442. PubMed ID: 17525752 doi:10.1038/nri2094

  • 11.

    Ciolac EG, Rodrigues da Silva JM. Resistance training as a tool for preventing and treating musculoskeletal disorders. Sports Med. 2016;46(9):12391248. PubMed ID: 26914266 doi:10.1007/s40279-016-0507-z

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol. 2012;2(2):11431211. PubMed ID: 23798298

  • 13.

    Pedersen BK, Saltin B. Exercise as medicine: evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports. 2015;25(suppl 3):172. doi:10.1111/sms.12581

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD. Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int. 2011;31(11):14091417. PubMed ID: 21800117 doi:10.1007/s00296-011-1999-3

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146e603. PubMed ID: 28122885 doi:10.1161/CIR.0000000000000485

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473(7347):317325. PubMed ID: 21593864 doi:10.1038/nature10146

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):11351143. PubMed ID: 11877368 doi:10.1161/hc0902.104353

  • 18.

    Ammirati E, Cianflone D, Vecchio V, et al. Effector memory T cells are associated with atherosclerosis in humans and animal models. J Am Heart Assoc. 2012;1(1):2741. PubMed ID: 23130116 doi:10.1161/xJAHA.111.000125

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Yu HT, Park S, Shin EC, Lee WW. T cell senescence and cardiovascular diseases. Clin Exp Med. 2016;16(3):257263. PubMed ID: 26188489 doi:10.1007/s10238-015-0376-z

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Fulop T, Dupuis G, Witkowski JM, Larbi A. The role of immunosenescence in the development of age-related diseases. Rev Invest Clin. 2016;68(2):8491. PubMed ID: 27103044

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Bergstrom I, Backteman K, Lundberg A, Ernerudh J, Jonasson L. Persistent accumulation of interferon-gamma-producing CD8+CD56+ T cells in blood from patients with coronary artery disease. Atherosclerosis. 2012;224(2):515520. PubMed ID: 22882906

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Liuzzo G, Biasucci LM, Trotta G, et al. Unusual CD4+CD28null T lymphocytes and recurrence of acute coronary events. J Am Coll Cardiol. 2007;50(15):14501458. PubMed ID: 17919564 doi:10.1016/j.jacc.2007.06.040

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Tae Yu H, Youn J-C, Lee J, et al. Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction. Cell Mol Immunol. 2015;12(4):466473. PubMed ID: 25152079 doi:10.1038/cmi.2014.74

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Youn JC, Yu HT, Lim BJ, et al. Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension. 2013;62(1):126133. PubMed ID: 23716586 doi:10.1161/HYPERTENSIONAHA.113.00689

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Ciolac EG, Bocchi EA, Greve JM, Guimaraes GV. Heart rate response to exercise and cardiorespiratory fitness of young women at high familial risk for hypertension: effects of interval vs continuous training. Eur J Cardiov Prev Rehabil. 2011;18(6):824830. doi:10.1177/1741826711398426

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Ciolac EG, Bocchi EA, Bortolotto LA, Carvalho VO, Greve JMD, Guimaraes GV. Effects of high-intensity aerobic interval training vs moderate exercise on hemodynamic, metabolic and neuro-humoral abnormalities of young normotensive women at high familial risk for hypertension. Hypert Res. 2010;33(8):836843. doi:10.1038/hr.2010.72

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Ciolac EG. High-intensity interval training and hypertension: maximizing the benefits of exercise? Am J Cardiovasc Dis. 2012;2(2):102110. PubMed ID: 22720199

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Ciolac EG, Bocchi EA, Bortolotto LA, Carvalho VO, Greve JM, Guimaraes GV. Haemodynamic, metabolic and neuro-humoral abnormalities in young normotensive women at high familial risk for hypertension. J Hum Hypertens. 2010;24(12):814822. PubMed ID: 20237500 doi:10.1038/jhh.2010.21

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Pantsulaia I, Ciszewski WM, Niewiarowska J. Senescent endothelial cells: potential modulators of immunosenescence and ageing. Ageing Res Rev. 2016;29:1325. PubMed ID: 27235855 doi:10.1016/j.arr.2016.05.011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Wenzel U, Turner JE, Krebs C, Kurts C, Harrison DG, Ehmke H. Immune mechanisms in arterial hypertension. J Am Soc Nephrol. 2016;27(3):677686. PubMed ID: 26319245 doi:10.1681/ASN.2015050562

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Harrison DG. The immune system in hypertension. Trans Am Clin Climatol Assoc. 2014;125:130138; discussion 138–140. PubMed ID: 25125726

  • 32.

    Bautista LE, Vera LM, Arenas IA, Gamarra G. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. J Hum Hypertens. 2005;19(2):149154. PubMed ID: 15361891 doi:10.1038/sj.jhh.1001785

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Harwani SC, Chapleau MW, Legge KL, Ballas ZK, Abboud FM. Neurohormonal modulation of the innate immune system is proinflammatory in the prehypertensive spontaneously hypertensive rat, a genetic model of essential hypertension. Circ Res. 2012;111(9):11901197. PubMed ID: 22904093 doi:10.1161/CIRCRESAHA.112.277475

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Marvar PJ, Thabet SR, Guzik TJ, et al. Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res. 2010;107(2):263270. PubMed ID: 20558826 doi:10.1161/CIRCRESAHA.110.217299

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Rea IM, McNerlan SE, Alexander DH, Armstrong ME. Blood pressure and TNF-alpha act synergistically to increase leucocyte CD11b adhesion molecule expression in the BELFAST study: implications for better blood pressure control in ageing. Age. 2013;35(1):197205. PubMed ID: 22086659 doi:10.1007/s11357-011-9326-1

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Xia S, Zhang X, Zheng S, et al. An update on inflamm-aging: mechanisms, prevention, and treatment. J Immunol Res. 2016;2016:8426874. PubMed ID: 27493973 doi:10.1155/2016/8426874

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Tam LS, Kitas GD, Gonzalez-Gay MA. Can suppression of inflammation by anti-TNF prevent progression of subclinical atherosclerosis in inflammatory arthritis? Rheumatology. 2014;53(6):11081119. doi:10.1093/rheumatology/ket454

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Angel K, Provan SA, Fagerhol MK, Mowinckel P, Kvien TK, Atar D. Effect of 1-year anti-TNF-alpha therapy on aortic stiffness, carotid atherosclerosis, and calprotectin in inflammatory arthropathies: a controlled study. Am J Hypertens. 2012;25(6):644650. PubMed ID: 22378036 doi:10.1038/ajh.2012.12

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Bozkurt B, Kribbs SB, Clubb FJ Jr, et al. Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats. Circulation. 1998;97(14):13821391. PubMed ID: 9577950 doi:10.1161/01.CIR.97.14.1382

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Diwan A, Dibbs Z, Nemoto S, et al. Targeted overexpression of noncleavable and secreted forms of tumor necrosis factor provokes disparate cardiac phenotypes. Circulation. 2004;109(2):262268. PubMed ID: 14699008 doi:10.1161/01.CIR.0000109642.27985.FA

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Dick SA, Epelman S. Chronic heart failure and inflammation: what do we really know? Circ Res. 2016;119(1):159176. PubMed ID: 27340274 doi:10.1161/CIRCRESAHA.116.308030

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Moro-Garcia MA, Echeverria A, Galan-Artimez MC, et al. Immunosenescence and inflammation characterize chronic heart failure patients with more advanced disease. Int J Cardiol. 2014;174(3):590599. PubMed ID: 24801091

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Chase NL, Sui X, Lee DC, Blair SN. The association of cardiorespiratory fitness and physical activity with incidence of hypertension in men. Am J Hypertens. 2009;22(4):417424. PubMed ID: 19197248 doi:10.1038/ajh.2009.6

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Gebel K, Ding D, Chey T, Stamatakis E, Brown WJ, Bauman AE. Effect of moderate to vigorous physical activity on all-cause mortality in middle-aged and older Australians. JAMA Intern Med. 2015;175(6):970977. PubMed ID: 25844882 doi:10.1001/jamainternmed.2015.0541

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Stewart RAH, Held C, Hadziosmanovic N, et al. Physical activity and mortality in patients with stable coronary heart disease. J Am Coll Cardiol. 2017;70(14):16891700. PubMed ID: 28958324 doi:10.1016/j.jacc.2017.08.017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Adams V, Niebauer J. reversing heart failure–associated pathophysiology with exercise: what actually improves and by how much? Heart Fail Clin. 2015;11(1):1728. PubMed ID: 25432471 doi:10.1016/j.hfc.2014.08.001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Ribeiro F, Alves AJ, Teixeira M, et al. Exercise training increases interleukin-10 after an acute myocardial infarction: a randomised clinical trial. Int J Sports Med. 2012;33(03):192198. doi:10.1055/s-0031-1297959

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Balen S, Vukelic-Damijani N, Persic V, et al. Anti-inflammatory effects of exercise training in the early period after myocardial infarction. Coll Antropol. 2008;32(1):285291. PubMed ID: 18494215

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Guimaraes GV, Ciolac EG, Carvalho VO, D’Avila VM, Bortolotto LA, Bocchi EA. Effects of continuous vs interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertens Res. 2010;33(6):627632. PubMed ID: 20379194

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50.

    Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):414. PubMed ID: 19896746 doi:10.1016/j.diabres.2009.10.007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Silventoinen K, Sans S, Tolonen H, et al. Trends in obesity and energy supply in the WHO MONICA Project. Int J Obes Relat Metab Disord. 2004;28(5):710718. PubMed ID: 15007395 doi:10.1038/sj.ijo.0802614

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52.

    Bastard JP. Recent advances in the relationship between obesity, inflammation and insulin resistance. Eur Cytokine Netw. 2006;17(1):412. PubMed ID: 16613757

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Moulin CM. Impact of adiposity on immunological parameters. Arq Bras Endocrinol Metabol. 2009;53(2):183189. doi:10.1590/S0004-27302009000200010

  • 54.

    Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:139239. PubMed ID: 24455420 doi:10.1155/2013/139239

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55.

    Kang YE, Kim JM, Joung KH, et al. The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PLoS One. 2016;11(4):e0154003. PubMed ID: 27101398 doi:10.1371/journal.pone.0154003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56.

    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425432. PubMed ID: 7984236 doi:10.1038/372425a0

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    Colberg SR, Albright AL, Blissmer BJ, et al. Exercise and type 2 diabetes: American College of Sports Medicine and the American Diabetes Association: joint position statement. Exercise and type 2 diabetes. Med Sci Sports Exerc. 2010;42(12):22822303. PubMed ID: 21084931

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 58.

    Alvarez C, Ramirez-Campillo R, Martinez-Salazar C, et al. Low-volume high-intensity interval training as a therapy for type 2 diabetes. Int J Sports Med. 2016;37(9):723729. PubMed ID: 27259099 doi:10.1055/s-0042-104935

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59.

    Umpierre D, Ribeiro PAB, Schaan BD, Ribeiro JP. Volume of supervised exercise training impacts glycaemic control in patients with type 2 diabetes: a systematic review with meta-regression analysis. Diabetologia. 2013;56(2):242251. PubMed ID: 23160642 doi:10.1007/s00125-012-2774-z

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60.

    Samaan MC, Marcinko K, Sikkema S, et al. Endurance interval training in obese mice reduces muscle inflammation and macrophage content independently of weight loss. Physiol Rep. 2014;2(5):pii: e12012. doi:10.14814/phy2.12012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 61.

    Kawanishi N, Mizokami T, Yano H, Suzuki K. Exercise attenuates M1 macrophages and CD8+ T cells in the adipose tissue of obese mice. Med Sci Sports Exerc. 2013;45(9):16841693. PubMed ID: 23954991 doi:10.1249/MSS.0b013e31828ff9c6

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62.

    Crissey JM, Jenkins NT, Lansford KA, et al. Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats. Am J Physiol Regul Integr Comp Physiol. 2014;306(8):R596R606. PubMed ID: 24523340 doi:10.1152/ajpregu.00493.2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63.

    Christiansen T, Paulsen SK, Bruun JM, Pedersen SB, Richelsen B. Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study. Am J Physiol Endocrinol Metab. 2010;298(4):E824E831. PubMed ID: 20086201 doi:10.1152/ajpendo.00574.2009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64.

    Steensberg A, Fischer CP, Keller C, Moller K, Pedersen BK. IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans. Am J Physiol Endocrinol Metab. 2003;285(2):E433E437. PubMed ID: 12857678 doi:10.1152/ajpendo.00074.2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65.

    Rezende MU, de Farias FES, da Silva CAC, Cernigoy CHA, de Camargo OP. Objective functional results in patients with knee osteoarthritis submitted to a 2-day educational programme: a prospective randomised clinical trial. BMJ Open Sport Exerc Med. 2016;2(1):e000200. PubMed ID: 28879035 doi:10.1136/bmjsem-2016-000200

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66.

    Bellamy N, Bradley L.Workshop on chronic pain, pain control, and patient outcomes in rheumatoid arthritis and osteoarthritis. Arthritis Rheum. 1996;3(39):357362. doi:10.1002/art.1780390302

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 67.

    Jahanbin I, Hoseini Moghadam M, Nazarinia MA, Ghodsbin F, Bagheri Z, Ashraf AR. The effect of conditioning exercise on the health status and pain in patients with rheumatoid arthritis: a randomized controlled clinical trial. Int J Community Based Nurs Midwifery. 2014;2(3):169176.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68.

    Cicuttini FM, Baker JR, Spector TD. The association of obesity with osteoarthritis of the hand and knee in women: a twin study. J Rheumatol. 1996(23):12211226.

    • Search Google Scholar
    • Export Citation
  • 69.

    Pottie P, Presle N, Terlain B, Netter P, Mainard D, Berenbaum F. Obesity and osteoarthritis: more complex than predicted. Ann Rheumatol Dis. 2006;65(11):14031405. doi:10.1136/ard.2006.061994

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 70.

    Aspden RM, Scheven BA, Hutchison JD. Osteoarthritis as a systemic disorder including stromal cell differentiation and lipid metabolism. Lancet. 2001;357(9262):11181120. PubMed ID: 11297982 doi:10.1016/S0140-6736(00)04264-1

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 71.

    Gomez R, Conde J, Scotece M, Gomez-Reino JJ, Lago F, Gualillo O. What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol. 2011;7(9):528536. PubMed ID: 21808287

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 72.

    Scotece M, Perez T, Conde J, et al. Adipokines induce pro-inflammatory factors in activated Cd4+ T cells from osteoarthritis patient. J Orthop Res. 2017;35(6):12991303. PubMed ID: 27472907 doi:10.1002/jor.23377

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 73.

    Scotece M, Conde J, Vuolteenaho K, et al. Adipokines as drug targets in joint and bone disease. Drug Discov Today. 2014;19(3):241258. PubMed ID: 23906693 doi:10.1016/j.drudis.2013.07.012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 74.

    Abella V, Scotece M, Conde J, et al. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat Rev Rheumatol. 2017;13(2):100109. PubMed ID: 28053336 doi:10.1038/nrrheum.2016.209

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 75.

    Takeda S, Elefteriou F, Karsenty G. Common endocrine control of body weight, reproduction, and bone mass. Annu Rev Nutr. 2003(23):403411.

    • Search Google Scholar
    • Export Citation
  • 76.

    Konrad A, Lehrke M, Schachinger V, et al. Resistin is an inflammatory marker of inflammatory bowel disease in humans. Eur J Gastroenterol Hepatol. 2007;19(12):10701074. PubMed ID: 17998831 doi:10.1097/MEG.0b013e3282f16251

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 77.

    Lago F, Dieguez C, Gómez-Reino J, Gualillo O. Adipokines as emerging mediators of immune response and inflammation. Nat Clin Pract Rheumatol. 2007;3(12):716724. PubMed ID: 18037931 doi:10.1038/ncprheum0674

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 78.

    Gosset M, Berenbaum F, Salvat C, et al. Crucial role of Visfatin/PBEF in matrix degradation and PGE2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum. 2008;58(5):13991409. PubMed ID: 18438860 doi:10.1002/art.23431

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 79.

    Maini RN, Brennan FM, Williams R, et al. TNF-alpha in rheumatpoid arthritis and prospects of anti-TNF therapy. Clin Exp Rheumatol. 1993;11(suppl 8):173175.

    • Search Google Scholar
    • Export Citation
  • 80.

    Moreno JA, Izquierdo MC, Sanchez-Niño MD, et al. The inflammatory cytokines TWEAK and TNFα reduce renal Klotho expression through NFκB. J Am Soc Nephrol. 2011;22(7):13151325. PubMed ID: 21719790 doi:10.1681/ASN.2010101073

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 81.

    Zhang F, Zhai G, Kato BS, et al. Association between Klotho gene and hand osteoarthritis in a female Caucasian population. Osteoarthritis Cartilage. 2007;15(6):624629. PubMed ID: 17270470 doi:10.1016/j.joca.2006.12.002

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 82.

    Tsezou A, Furuichi T, Satra M, Makrythanasis P, Ikegawa S, Malizos KN. Association of Klotho gene polymorphisms with knee osteoarthritis in Greek population. J Orthop Res 2008;26(11):14661470. PubMed ID: 18465812 doi:10.1002/jor.20634

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 83.

    Ciolac EG, Rodrigues-da-Silva JM. Resistance training as a tool for preventing and treating musculoskeletal disorders. Sports Med. 2016;46(9):12391248. PubMed ID: 26914266 doi:10.1007/s40279-016-0507-z

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 84.

    Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol. 2005;78(4):819835. PubMed ID: 16033812 doi:10.1189/jlb.0505247

  • 85.

    Verhoeven F, Tordi N, Prati C, Demougeot C, Mougin F, Wendling D. Physical activity in patients with rheumatoid arthritis. Joint Bone Spine. 2015;83(3):265270. PubMed ID: 26639220 doi:10.1016/j.jbspin.2015.10.002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 86.

    Strasser B, Schobersberger W. Evidence for resistance training as a treatment therapy in obesity. J Obes. 2011;2011:pii: 482564.

  • 87.

    Matsubara T, Miyaki A, Akazawa N, et al. Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women. Am J Physiol Heart Circ Physiol. 2014;306(3):H348H355. PubMed ID: 24322608 doi:10.1152/ajpheart.00429.2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 88.

    Santos-Dias A, MacKenzie B, Oliveira-Junior MC, Moyses RM, Consolim-Colombo FM, Vieira RP. Longevity protein Klotho is induced by a single bout of exercise. Br J Sports Med. 2017;51(6):549550. PubMed ID: 27251899 doi:10.1136/bjsports-2016-096139

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 89.

    Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195(5):557582. PubMed ID: 28128970 doi:10.1164/rccm.201701-0218PP

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 90.

    Barnes PJ. Senescence in COPD and its comorbidities. Annu Rev Physiol. 2017;79:517539. PubMed ID: 27959617 doi:10.1146/annurev-physiol-022516-034314

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 91.

    Schuliga M. NF-kappaB signaling in chronic inflammatory airway disease. Biomolecules. 2015;5(3):12661283. PubMed ID: 26131974 doi:10.3390/biom5031266

  • 92.

    Baker JR, Vuppusetty C, Colley T, et al. Oxidative stress dependent microRNA-34a activation via PI3Kα reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells. Sci Rep. 2016;6:35871. PubMed ID: 27767101 doi:10.1038/srep35871

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 93.

    Le Rouzic O, Pichavant M, Frealle E, Guillon A, Si-Tahar M, Gosset P. Th17 cytokines: novel potential therapeutic targets for COPD pathogenesis and exacerbations. Eur Respir J. 2017;50(4):pii:1602434. doi:10.1183/13993003.02434-2016

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 94.

    Yanagisawa S, Papaioannou AI, Papaporfyriou A, et al. Decreased serum sirtuin-1 in COPD. Chest. 2017;152(2):343352. PubMed ID: 28506610 doi:10.1016/j.chest.2017.05.004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 95.

    Aghapour M, Raee P, Moghaddam SJ, Hiemstra PS, Heijink IH. Airway epithelial barrier dysfunction in COPD: role of cigarette smoke exposure. Am J Respir Cell Mol Biol. 2018;58(2):157169. PubMed ID: 28933915 doi:10.1165/rcmb.2017-0200TR

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 96.

    Lin F, Liao C, Sun Y, et al. Hydrogen sulfide inhibits cigarette smoke-induced endoplasmic reticulum stress and apoptosis in bronchial epithelial cells. Front Pharmacol. 2017;8:675. PubMed ID: 29033840 doi:10.3389/fphar.2017.00675

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 97.

    Koo HK, Kang HK, Song P, Park HK, Lee SS, Jung H. Systemic white blood cell count as a biomarker associated with severity of chronic obstructive lung disease. Tuberc Respir Dis. 2017;80(3):304310. PubMed ID: 28747965 doi:10.4046/trd.2017.80.3.304

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 98.

    Xiong W, Xu M, Zhao Y, Wu X, Pudasaini B, Liu JM. Can we predict the prognosis of COPD with a routine blood test? Int J Chron Obstruct Pulmon Dis. 2017;12:615625. PubMed ID: 28243079 doi:10.2147/COPD.S124041

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 99.

    Cho WK, Lee CG, Kim LK. COPD as a disease of immunosenescence. Yonsei Med J. 2019;60(5):407413. PubMed ID: 31016901 doi:10.3349/ymj.2019.60.5.407

  • 100.

    Barnes PJ. Pulmonary diseases and ageing. Subcell Biochem. 2019;91:4574. PubMed ID: 30888649

  • 101.

    Kureya Y, Kanazawa H, Ijiri N, et al. Down-regulation of soluble alpha-Klotho is associated with reduction in serum Irisin levels in chronic obstructive pulmonary disease. Lung. 2016;194(3):345351. PubMed ID: 27140192 doi:10.1007/s00408-016-9870-7

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 102.

    Toledo AC, Magalhaes RM, Hizume DC, et al. Aerobic exercise attenuates pulmonary injury induced by exposure to cigarette smoke. Eur Resp J. 2012;39(2):254264doi:10.1183/09031936.00003411.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 103.

    Nesi RT, de Souza PS, Dos Santos GP, et al. Physical exercise is effective in preventing cigarette smoke-induced pulmonary oxidative response in mice. Int J Chron Obstruct Pulmon Dis. 2016;11:603610. PubMed ID: 27042047 doi:10.2147/COPD.S93958

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 104.

    Rodrigues Brandao-Rangel MA, Bachi ALL, Oliveira-Junior MC, et al. Exercise inhibits the effects of smoke-induced COPD involving modulation of STAT3. Oxid Med Cell Longev. 2017;2017:13. doi:10.1155/2017/6572714

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 105.

    Chan SH, Hung CH, Shih JY, et al. Exercise intervention attenuates hyperhomocysteinemia-induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX-1 signaling. Redox Biol. 2018;14:116125. PubMed ID: 28888894 doi:10.1016/j.redox.2017.08.016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 106.

    Toledo-Arruda AC, Vieira RP, Guarnier FA, et al. Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD. J Appl Physiol. 2017;123(3):674683. doi:10.1152/japplphysiol.00819.2016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 107.

    Vieira RP, Toledo AC, Silva LB, et al. Anti-inflammatory effects of aerobic exercise in mice exposed to air pollution. Med Sci Sports Exerc. 2012;44(7):12271234. PubMed ID: 22297803 doi:10.1249/MSS.0b013e31824b2877

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 108.

    Silva-Renno A, Baldivia GC, Oliveira-Junior MC, et al. Exercise performed concomitantly with particulate matter exposure inhibits lung injury. Int J Sports Med. 2018;39(2):133140. PubMed ID: 29161746 doi:10.1055/s-0043-121147

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 109.

    do Nascimento ES, Sampaio LM, Peixoto-Souza FS, et al. Home-based pulmonary rehabilitation improves clinical features and systemic inflammation in chronic obstructive pulmonary disease patients. Int J Chron Obstruct Pulmon Dis. 2015;10:645653. PubMed ID: 25848241

    • Search Google Scholar
    • Export Citation
  • 110.

    Abd El-Kader SM, Al-Jiffri OH, Al-Shreef FM. Plasma inflammatory biomarkers response to aerobic versus resisted exercise training for chronic obstructive pulmonary disease patients. Afr Health Sci. 2016;16(2):507515. PubMed ID: 27605966 doi:10.4314/ahs.v16i2.19

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 111.

    Tanasescu M, Leitzmann MF, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Exercise type and intensity in relation to coronary heart disease in men. JAMA. 2002;288(16):19942000. PubMed ID: 12387651 doi:10.1001/jama.288.16.1994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 112.

    Wisloff U, Nilsen TI, Droyvold WB, Morkved S, Slordahl SA, Vatten LJ. A single weekly bout of exercise may reduce cardiovascular mortality: how little pain for cardiac gain? ‘The HUNT study, Norway’. Eur J Cardiovasc Prev Rehabil. 2006;13(5):798804. PubMed ID: 17001221

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 113.

    Shiroma EJ, Sesso HD, Moorthy MV, Buring JE, Lee IM. Do moderate-intensity and vigorous-intensity physical activities reduce mortality rates to the same extent? J Am Heart Assoc. 2014;3(5):e000802. PubMed ID: 25326527 doi:10.1161/JAHA.114.000802

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 114.

    Janssen I, Ross R. Vigorous intensity physical activity is related to the metabolic syndrome independent of the physical activity dose. Int J Epidemiol. 2012;41(4):11321140. PubMed ID: 22447838 doi:10.1093/ije/dys038

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 115.

    Tjonna AE, Lee SJ, Rognmo O, et al. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation. 2008;118(4):346354. PubMed ID: 18606913

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 116.

    Wisloff U, Stoylen A, Loennechen JP, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007;115(24):30863094. PubMed ID: 17548726

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 117.

    Trapp EG, Chisholm DJ, Freund J, Boutcher SH. The effects of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women. Int J Obes. 2008;32(4):684691. doi:10.1038/sj.ijo.0803781

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 118.

    Viana AA, Fernandes B, Alvarez C, Guimaraes GV, Ciolac EG. Prescribing high-intensity interval exercise by RPE in individuals with type 2 diabetes: metabolic and hemodynamic responses. Appl Physiol Nutr Metab. 2019;44(4):348356. PubMed ID: 30230920 doi:10.1139/apnm-2018-0371

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 119.

    Alvarez C, Ramirez-Campillo R, Martinez-Salazar C, Castillo A, Gallardo F, Ciolac EG. High-intensity interval training as a tool for counteracting dyslipidemia in women. Int J Sports Med. 2018;39(5):397406. PubMed ID: 29564840 doi:10.1055/s-0044-100387

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 120.

    Wen CP, Wai JP, Tsai MK, Chen CH. Minimal amount of exercise to prolong life: to walk, to run, or just mix it up? J Am Coll Cardiol. 2014;64(5):482484. PubMed ID: 25082582 doi:10.1016/j.jacc.2014.05.026

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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