Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-22T22:15:05.089Z Has data issue: false hasContentIssue false
  • English
  • Français

Ageing, exercise and the chemistry of inflammation

Published online by Cambridge University Press:  29 April 2015

SC Allen
SC Allen*
Affiliation:
The Royal Bournemouth Hospital and Centre for Postgraduate Medical Research and Education, University of Bournemouth, UK
*
Address for correspondence: Professor SC Allen, The Royal Bournemouth Hospital, Castle Lane East, Bournemouth, Dorset BH7 7DW, UK. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Exercise has a complex influence on the biochemical markers of inflammation that includes suppression of pro-inflammatory cytokines and promotion of anti-inflammatory cytokines. The magnitude of this effect is large for prolonged activity at high work rates. People who are able to perform regular mild–moderate exercise have lower baseline pro-inflammatory cytokine levels that appear to be associated with a number of health benefits, including reduced all-cause mortality. These effects extend into old age. Interleukin-6 (IL-6), a pleiotropic myokine released by active muscle cells, appears to play a central role in these observed phenomena, though the mechanisms of action are intricate and incompletely understood. The minimum threshold of the exercise–cytokine dose–response, if any, has not been clearly characterized. Therefore, the potential to influence cytokine activity and reduce age-associated inflammation in very aged or frail people able to perform only very low levels of physical activity is unknown.

Keywords

inflammationexercisecytokineold agehealth status
Type
Review Article
Information
Reviews in Clinical Gerontology , Volume 25 , Issue 2 , May 2015 , pp. 73 - 80
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Harris, HA. Sport in Greece and Rome. New York: Cornell University Press; 1972.Google Scholar
2 Forbes, CA. Greek Physical Education. New York: The Century Company; 1929.Google Scholar
3 Aristotle. Politics. In Rakkam, H, Aristotle in three volumes. London: Heinemann; 1944.Google Scholar
4 Dalleck, LC, Krovitz, L. The history of fitness. IDEA Health and Fitness Source 2002; 20: 26–33.Google Scholar
5 NICE guideline CG83. Rehabilitation after critical illness. Available at: www.nice.org.uk/guidance/cg83 (accessed 15 January 2015).Google Scholar
6 NICE guideline CG162. Stroke rehabilitation: long-term rehabilitation after stroke. Available at: www.nice.org.uk/guidance/cg162 (accessed 15 January 2015).Google Scholar
7 Shabo, Y, Lotem, J, Rubenstein, M et al. The myeloid blood cell differentiation-inducing protein MGI-2A is interleukin-6. Blood 1988; 72: 2070–73.Google Scholar
8 Beschin, A, Bilej, M, Torreele, E, De Baetselier, P. On the existence of cytokines in invertebrates. Cell Molec Life Sci 2001; 58: 801–14.Google Scholar
9 Kishimoto, T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther 2006; 8: 1–10.Google Scholar
10 Pedersen, BK. The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem 2006; 42: 105–17.Google Scholar
11 Woods, JA, Wilund, KR, Martin, SA, Kistler, BM. Exercise, inflammation and aging. Aging Dis 2012; 3: 130–40.Google Scholar
12 Bruunsgaard, H, Pedersen, BK. Age-related inflammatory cytokines and disease. Immunol Allergy Clin North Am 2003; 23: 15–39.Google Scholar
13 Chung, HY, Cesari, M, Anton, S et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 2009; 8: 18–30.Google Scholar
14 Caspersen, CJ, Pereira, MA, Curran, KM. Changes in physical activity patterns in the United States, by sex and cross-sectional age. Med Sci Sports Exerc 2000; 32: 1601–9.Google Scholar
15 Driver, JA, Djousse, L, Logroscino, G, Gaziano, JM, Kurth, T. Incidence of cardiovascular disease and cancer in advanced age: prospective cohort study. BMJ 2008; 337: a2467.Google Scholar
16 Cowie, CC, Rust, KF, Byrd-Holt, DD et al. Prevalence of diabetes and impaired fasting glucose in adults in the US population: NHANES survey 1999–2002. Diabetes Care 2006; 29: 1263–68.Google Scholar
17 Starr, ME, Saito, H. Sepsis in old age: review of human and animal studies. Aging Dis 2014; 5: 126–36.Google Scholar
18 Boyd, AR, Orihuela, CJ. Dysregulated inflammation as a risk factor for pneumonia in the elderly. Aging Dis 2011; 2: 487–500.Google Scholar
19 Kalaria, RN, Maestre, GE, Arizaga, R et al. Alzheimer's disease and vascular demntia in developing countries: prevalence, management, and risk factors. Lancet Neurol 2008; 7: 812–26.Google Scholar
20 Coresh, J, Selvin, E, Stevens, LA et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298: 2038–47.Google Scholar
21 Dagenais, S, Garbedian, S, Wai, EK. Systematic review of the prevalence of radiographic primary hip osteoarthritis. Clin Orthop Relat Res 2009; 467: 623–37.Google Scholar
22 Ballou, SP, Lozanski, FB, Hodder, S et al. Quantitative and qualitative alterations of acute-phase proteins in healthy elderly persons. Age Ageing 1996; 25: 224–30.Google Scholar
23 Ershler, WB, Sun, WH, Binkley, N et al. Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. Lymphokine Cytokine Res 1993; 12: 225–30.Google Scholar
24 Wei, J, Xu, H, Davies, JL, Hemmings, GP. Increase in plasma IL-6 concentration with age in healthy subjects. Life Sci 1992; 51: 1953–56.Google Scholar
25 Ahluwalia, N, Mastro, AM, Ball, R, Miles, MP, Rajendra, R, Handte, G. Cytokine production by stimulated mononuclear cells did not change with aging in apparently healthy, well-nourished women. Mech Ageing Dev 2001; 122: 1269–79.Google Scholar
26 Beharka, AA, Meydani, M, Wu, D, Leka, LS, Meydani, A, Meydani, SN. Interleukin-6 production does not increase with age. J Gerontol A Biol Sci Med Sci 2001; 56: B81–88.Google Scholar
27 Kabagambe, EK, Judd, SE, Howard, VJ et al. Inflammation biomarkers and risk of all-cause mortality in the RCARDS cohort. Am J Epidemiol 2011; 174: 284–92.Google Scholar
28 DeMartinis, M, Franceschi, C, Monti, D, Ginaldi, L. Inflammation markers predicting frailty and mortality in the elderly. Exp Molec Pathol 2006; 80: 219–27.Google Scholar
29 Jensen, GL. Inflammation: roles in aging and sarcopenia. J Parenter Enteral Nutr 2008; 32: 656–59.Google Scholar
30 Penninx, BW, Kritchevsky, SB, Newman, AB et al. Inflammatory markers and incident mobility limitation in the elderly. J Am Geriatr Soc 2004; 52: 1105–13.Google Scholar
31 Christian, LM, Glaser, R, Porter, K, Malarkey, WB, Beversdorf, D, Kiecolt-Glaser, JK. Poorer self-related health is associated with elevated inflammatory markersamong older adults. Psychoneuroendocrinology 2011; 36: 1495–504.Google Scholar
32 Michaud, M, Balardy, L, Moulis, G et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc 2013; 14: 877–82.Google Scholar
33 Golbidi, S, Laher, I. Exercise and the aging endothelium. J Diabetes Res 2013; available at: http://dx.doi.org/10.1155/2013/789607 (accessed 12 January 2015).Google Scholar
34 Bruunsgaard, H, Skinhoj, P, Qvist, J, Pedersen, BK. Elderly humans show prolonged in vivo inflammatory activity during pneumococcal infections. J Infect Dis 1999; 180: 551–54.Google Scholar
35 Krabbe, KS, Bruunsgaard, H, Hansen, CM et al. Ageing is associated with a prolonged fever in human endotoxemia. Clin Diagn Lab Immunol 2001; 8: 333–38.Google Scholar
36 Wu, J, Xia, S, Kalonis, B, Wan, W, Sun, T. The role of oxidative stress and inflammation in cardiovascular aging. Bio Med Res Internat 2014; available at: http://dx.doi.org/10.1155/2014/615312 (accessed 20 January 2015).Google Scholar
37 McFarlin, BK, Flynn, MG, Campbell, WW et al. Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. J Gerontol A Biol Sci Med Sci 2006; 61: 388–93.Google Scholar
38 Rotman-Pikielny, P, Roash, V, Chen, O, Limor, R, Stern, N, Gur, HG. Serum cortisol levels in patients admitted to the department of medicine: prognostic correlations and effects of age, infection and co-morbidity. Am J Med Sci 2006; 332: 61–67.Google Scholar
39 Johnson, DB, Kip, KE, Marroquin, OC et al. Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women. Circulation 2004; 109: 726–32.Google Scholar
40 Beavers, KM, Brinkley, TE, Nicklas, BJ. Effect of exercise on chronic inflammation. Clin Chem Acta 2010; 411: 785–93.Google Scholar
41 Everett, BM, Bansal, S, Rifai, N, Buring, JE, Ridker, PM. Interleukin-18 and the risk of future cardiovascular disease among initially healthy women. Atherosclerosis 2009; 202: 282–88.Google Scholar
42 Gokkusu, C, Aydin, M, Ozkok, E et al. Influences of genetic variants in interleukin-15 gene and interleukin-15 levels on coronary heart disease. Cytokine 2009; 49: 58–63.Google Scholar
43 Caruso, DJ, Carmack, AJ, Lockeshwar, VB, Duncan, RC, Soloway, MS, Lockeshwar, BL. Osteopontin and interleukin-8 expression is independently associated with prostate cancer recurrence. Clin Cancer Res 2008; 14: 4111–18.Google Scholar
44 Gauldie, J, Saunder, DN, McAdam, KP, Dinarello, CA. Purified interleukin-1 from human monocytes stimulates acute phase protein synthesis by rodent hepatocytes in vitro . Immunology 1987; 60: 203–7.Google Scholar
45 Mahesh, VN. Albumin: a marker of inflammation. BMJ 2006; 333: 1044.Google Scholar
46 Erta, M, Quintana, A, Hildago, J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 2012; 8: 1254–66.Google Scholar
47 Allison, DJ, Ditor, DS. The common inflammatory etiology of depression and cognitive impairment: a therapeutic target. J Neuroinflammation 2014; available at: http://dx.doi:10.1186/s12974-014-0151-1 (accessed 2 February 2015).Google Scholar
48 Sparkman, NL, Johnson, RW. Neuroinflammation associated with aging sensitizes the brain to the effects of infection or stress. Neuroimmunomodulation 2008; 15: 323–30.Google Scholar
49 Zotova, E, Nicoll, JAR, Kalaria, R, Holmes, C, Bocke, D. Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy. Alzheimers Res Ther 2010; 2: 1–8.Google Scholar
50 Ohman, H, Savikko, N, Strandberg, TE, Pitkala, KH. Effect of physical exercise on cognitive performance in older adultswith mild cognitive impairment or dementia: a systematic review. Dement Geriatr Cogn Disord 2014; 38: 347–65.Google Scholar
51 Vinik, AI, Erbas, T, Casellini, CM. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. Diabetes Investig 2013; 4: 4–18.Google Scholar
52 Pal, M, Febbraio, MA, Whitham, M. From cytokine to myokine: the emerging role of interleukin-6 in metabolic regulation. Immunol Cell Biol 2014; 92: 331–39.Google Scholar
53 Pedersen, BK, Febbraio, M. Muscle-derived interleukin-6: a possible link between skeletal muscle, adipose tissue, liver and brain. Brain Behav Immun 2005; 19: 371–76.Google Scholar
54 Kishimoto, T. IL-6: from its discovery to clinical applications. Internat Immunol 2010; 22: 347–52.Google Scholar
55 Mikkelsen, UR, Couppe, C, Karlsen, A et al. Life-long endurance exercise in humans: circulating levels of inflammatory markers and leg muscle size. Mech Ageing Dev 2013; 134: 531–40.Google Scholar
56 Pedersen, BK, Steensberg, A, Fischer, C et al. Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil 2003; 24: 113–19.Google Scholar
57 Pedersen, AMW, Pedersen, BK. The anti-inflammatory effect of exercise. J Appl Physiol 2005; 98: 1154–62.Google Scholar
58 Pedersen, BK, Steenberg, A, Schjerling, P. Exercise and interleukin-6. Curr Opin Hematol 2001; 8: 137–41.Google Scholar
59 Fischer, CP. Interleukin-6 in acute exercise and training; what is the biological relevance? Exerc Immunol Rev 2006; 12: 6–33.Google Scholar
60 Woods, JA, Veira, VJ, Keylock, KT. Exercise, inflammation and innate immunity. Immunol Allergy Clin N Am 2009; 29: 381–93.Google Scholar
61 Pedersen, BK. Exercise-induced myokines and their role in chronic disease. Brain Behav Immun 2011; 25: 811–16.Google Scholar
62 Brandt, C, Pedersen, BK. The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol 2010; available at: http://dx.doi.org/10.1155/2010/520258 (accessed 3 January 2015).Google Scholar
63 Ekelund, U, Ward, HA, Norat, T et al. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition study (EPIC). Am J Clin Nutr 2015; available at: http://dx.doi.org/10.3954/ajcn.100065 (accessed 11 February 2015).Google Scholar
64 Tuomilehto, J, Lindstrom, J, Eriksson, JG et al. Prevention of type 2 diabetes mellitus by changes of lifestyle among subjects with impaired glucose tolerance. N Eng J Med 2001; 344: 1343–50.Google Scholar
65 Arem, H, Moore, SC, Park, Y et al. Physical activity and cancer-specific mortality in the NIH-AARP Diet and Health Study cohort. Int J Cancer 2014; 135: 423–31.Google Scholar
66 Angevaren, M, Aufdemkampe, G, Verhaar, HJ, Aleman, A, Vanhees, L. Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database Syst Rev 2008; available at: http://dx.doi.org/10.1002/14651858.CD005381 (accessed 2 February 2015).Google Scholar
67 Windle, G, Hughes, D, Linck, P, Russell, I, Woods, B. Is exercise effective in promoting mental wellbeing in older age? A systematic review. Aging Ment Health 2010; 14: 152–69.Google Scholar
68 BTS Guideline on pulmonary rehabilitation in adults. Thorax 2013; 68 (suppl 2): 1–36.Google Scholar
69 NICE guideline CG172. Myocardial infarction – secondary prevention. Available at: www.nice.org.uk/guidance/cg172 (accessed 1 February 2015).Google Scholar
70 Colbert, LH, Visser, M, Simonsick, EM et al. Physical activity, exercise and inflammatory markers in older adults. J Am Ger Soc 2004; 52: 1098–104.Google Scholar
71 Taaffe, DR, Harris, TB, Ferrucci, L, Rowe, J, Seeman, TE. Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons. J Gerontol A Biol Sci Med 2000; 55: 709–15.Google Scholar
72 Geffken, DF, Cushman, M, Burke, GC, Polak, JF, Sakkinen, PA, Tracey, RP. Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 2001; 153: 242–50.Google Scholar
73 Wannamethee, SG, Lowe, GDO, Whincup, PH, Rumley, A, Walker, M, Lennon, L. Physical activity and hemostatic variables in elderly men. Circulation 2002; 105: 1785–90.Google Scholar
74 Elosua, R, Bartali, B, Ordovas, JM, Corsi, AM, Laurentian, F, Ferrucci, L. Association between physical activity, physical performance and inflammatory biomarkers in an elderly population: the CHIANTI study. J Gerontol A Biol Sci Med Sci 2005; 60: 760–67.Google Scholar
75 Hamer, M, Sabia, S, Batty, GD et al. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study. Circulation 2012; 126: 928–33.Google Scholar
76 Nicklas, BJ, Ambrosius, W, Messier, SP et al. Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am J Clin Nutr 2004; 79: 544–51.Google Scholar
77 Hamer, M, Steptoe, A. Prospective study of physical fitness, adiposity and inflammatory markers in healthy middle-aged man and women. Am J Clin Nutr 2009; 89: 85–89.Google Scholar
78 Valentine, RJ, Vieira, VJ, Woods, JA, Evans, EM. Stronger relationship between central adiposity and C-reactive protein in older women than men. Menopause 2009; 16: 84–89.Google Scholar