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TNF-α, IL6, and IL10 polymorphisms and the effect of physical exercise on inflammatory parameters and physical performance in elderly women


High levels of inflammatory mediators are associated with reduced physical capabilities and muscle function in the elderly. Single nucleotide polymorphisms (SNPs) may affect the expression and synthesis of these molecules, thus influencing the intensity of the inflammatory response and susceptibility to certain diseases. Physical exercise may attenuate age-related chronic inflammation and improve physical performance. This study evaluated the interaction between the SNP rs1800629 in TNF-α, rs1800795 in IL6, and rs1800896 in IL10 and the effect of physical exercise on physical performance and inflammation in elderly women. There was a significant interaction between rs1800629 and the effect of exercise on physical performance and between the combined 3-SNP genotype and changes in physical performance in response to exercise. These SNPs did not influence the effect of exercise on inflammatory parameters. Elderly women with a combination of genotypes associated with an anti-inflammatory profile (low TNF-α and IL-6 production, high IL-10 production) showed better physical performance independent of exercise modality, evidence of an interactive influence of genetic and environmental factors on improving physical performance in elderly women.

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  1. Aderka D, Engelmann H, Shemer-Avni Y, Hornik V, Galil A, Sarov B, Wallach D (1992) Variation in serum levels of the soluble TNF receptors among healthy individuals. Lymphokine Cytokine Res 11:157–159

  2. Beavers KM, Brinkley TE, Nicklas BJ (2010) Effect of exercise training on chronic inflammation. Clin Chim Acta 411:785–793

  3. Bertolucci PH, Brucki SM, Campacci SR, Juliano Y (1994) O Mini-exame do estado mental em uma população geral: impacto da escolaridade. Arq Neuropsiquiatr 52:1–7

  4. Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, Oksenberg J et al (1999) Cytokine gene polymorphism in human disease: on-line database. Genes Immun 1:3–19

  5. Cederholm T, Persson M, Andersson P, Stenvinkel P, Nordfors L, Madden J, Vedin I et al (2007) Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients. J Intern Med 262:215–223

  6. Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, Minson CT, Nigg CR, Salem GJ, Skinner JS (2009) American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc 41:1510–1530

  7. Coelho FM, Reis HJ, Nicolato R, Romano-Silva MA, Teixeira MM, Bauer ME, Teixeira AL (2008) Increased serum levels of inflammatory markers in chronic institutionalized patients with schizophrenia. Neuroimmunomodulation 15:140–144

  8. Dato S, Krabbe KS, Thinggaard M, Pedersen BK, Christensen K, Bruunsgaard H, Christiansen L (2010) Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians. J Gerontol A Biol Sci Med Sci 65:225–235

  9. Folstein MF, Folstein SE, McHugh PR (1975) Minimental state. A practical method for grading the cognitive status of patients for the clinician. J Psychiatr Res 12:189–198

  10. Gallucci M, Amici GP, Ongaro F, Gajo GB, De Angeli S, Forloni GL, Albani D et al (2007) Associations of the plasma interleukin-6 (IL-6) levels with disability and mortality in the elderly in the Treviso Longeva (TRELONG) Study. Arch Gerontol Geriatr Suppl 1:193–198

  11. Gu MO, Conn VS (2008) Meta-analysis of the effects of exercise interventions on functional status in older adults. Res Nurs Health 31:594–603

  12. Karimi M, Goldie LC, Cruickshank MN, Moses EK, Abraham LJ (2009) A critical assessment of the factors affecting reporter gene assays for promoter SNP function: a reassessment of −308 TNF polymorphism function using a novel integrated reporter system. Eur J Hum Genet 17:1454–1462

  13. Khabour OF, Barnawi JM (2010) Association of longevity with IL-10–1082G/A and TNF-alpha-308G/A polymorphisms. Int J Immunogenet 37:293–298

  14. Kilpelainen TO, Laaksonen DE, Lakka TA, Herder C, Koenig W, Lindstrom J, Eriksson JG et al (2010) The rs1800629 polymorphism in the TNF gene interacts with physical activity on the changes in C-reactive protein levels in the Finnish Diabetes Prevention Study. Exp Clin Endocrinol Diabetes 118:757–759

  15. Kohut ML, McCann DA, Russell DW, Konopka DN, Cunnick JE, Franke WD, Castillo MC et al (2006) Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of β-blockers, BMI, and psychosocial factors in older adults. Brain Behav Immun 20:201–209

  16. Krabbe KS, Perdersen M, Bruunsgaard H (2004) Inflammatory mediators in the elderly. Exp Gerontol 39:687–699

  17. Kubaszek A, Pihlajamaki J, Komarovski V, Lindi V, Lindstrom J, Eriksson J, Valle TT et al (2003) Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study. Diabetes 52:1872–1876

  18. Latham NK, Bennett DA, Stretton CM, Anderson CS (2004) Systematic review of progressive resistance strength training in older adults. J Gerontol A Biol Sci Med Sci 59:48–61

  19. Lio D, Scola L, Crivello A, Colonna RG, Candore G, Bonafè M, Cavallone L et al (2003) Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10 –1082 promoter SNP and its interaction with TNF −308 promoter SNP. J Med Genet 40:296–299

  20. Liu D, Metter EJ, Ferrucci L, Roth SM (2008) TNF promoter polymorphisms associated with muscle phenotypes in humans. J Appl Physiol 105:859–867

  21. Lustosa LP, Coelho FM, Silva JP, Pereira DS, Parentoni AN, Dias JM, Dias RC, Pereira LS (2010) The effects of a muscle resistance program on the functional capacity, knee extensor muscle strength and plasma levels of IL-6 and TNF-alpha in pre-frail elderly women: a randomized crossover clinical trial—a study protocol. Trials 11:82

  22. Maat MPM, Bladbjerg EM, Hjelmborg JB, Bathum L, Jespersen J, Christensen K (2004) Genetic influence on inflammation variables in the elderly. Arterioscler Thromb Vasc Biol 24:2168–2173

  23. Mohamed-Ali V, Goodrick S, Bulmer K, Holly JM, Yudkin JS, Coppack SW (1999) Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. Am J Physiol 277:E971–E975

  24. Nicklas BJ, Mychaleckyj J, Kritchevsky S, Palla S, Lange LA, Lange EM, Messier SP et al (2005) Physical function and its response to exercise: associations with cytokine gene variation in older adults with knee osteoarthritis. J Gerontol A Biol Sci Med Sci 60A:1292–1298

  25. Oberbach A, Lehmann S, Kirsch K, Krist J, Sonnabend M, Linke A, Tonjes A et al (2008) Long-term exercise training decreases interleukin-6 (IL-6) serum levels in subjects with impaired glucose tolerance: effect of the -174G/C variant in IL-6 gene. Eur J Endocrinol 159:129–136

  26. Oliveira DM, Narciso FM, Santos ML, Pereira DS, Coelho FM, Dias JM, Pereira LS (2008) Muscle strength but not functional capacity is associated with plasma interleukin-6 levels of community-dwelling elderly women. Braz J Med Biol Res 41:1148–1153

  27. Olivieri F, Bonafè M, Cavallone L, Giovagnetti S, Marchegiani F, Cardelli M, Mugianesi E et al (2002) The -174C/G locus affects in vitro/in vivo IL-6 production during aging. Exp Gerontol 37:309–314

  28. Pereira DS, Garcia DM, Narciso FM, Santos ML, Dias JM, Queiroz BZ, Souza ER et al (2011) Effects of 174G/C polymorphism in the promoter region of the interleukin-6 gene on plasma IL-6 levels and muscle strength in elderly women. Braz J Med Biol Res 44:123–129

  29. Pereira DS, Queiroz BZ, Mateo ECC, Assumpção AM, Felício DC, Miranda AS, Anjos DMC et al (2012) Interaction between cytokines gene polymorphisms and the effect of physical exercise on clinical and inflammatory parameters in the elderly women: study protocol for a randomized controlled trial. Trials 13:134

  30. Petersen AMW, Pedersen BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol 98:1154–1162

  31. Phillips MD, Flynn MG, McFarlin BK, Stewart LK, Timmerman KL (2010) Resistance training at eight-repetition maximum reduces the inflammatory milieu in elderly women. Med Sci Sports Exerc 42:314–325

  32. Podsiadlo D, Richardson S (1991) The Timed Up & Go: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 39:142–148

  33. Reid MB, Li Y-P (2001) Tumor necrosis factor-α and muscle wasting: a cellular perspective. Respir Res 2:269–272

  34. Roth SM, Schrager MA, Lee MR, Metter EJ, Hurley BF, Ferrell RE (2003) Interleukin-6 (IL-6) genotype is associated with fat-free mass in men but not women. J Gerontol A Biol Sci Med Sci 58A:1085–1088

  35. Schaap LA, Pluijm SM, Deeg DJ, Harris TB, Kritchevsky SB, Newman AB, Colbert LH et al (2009) Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol A Biol Sci Med Sci 64:1183–1189

  36. Stephens JW, Hurel SJH, Lowe GDO, Rumley A, Humphries SE (2007) Association between plasma IL-6, the IL-6 -174G>C gene variant and the metabolic syndrome in type 2 diabetes mellitus. Mol Genet Metab 90:422–428

  37. Tiainen K, Hurme M, Hervonen A, Luukkaala T, Jylha M (2010) Inflammatory markers and physical performance among nonagenarians. J Gerontol A Biol Sci Med Sci 65:658–663

  38. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 24:1–8

  39. VanSwearingen JM, Brach JS (2001) Making geriatric assessment work: selecting useful measures. Phys Ther 81:1233–1252

  40. Visser M, Goodpaster BH, Kritchevsky SB, Newman A, Nevitt M, Rubin SM, Simonsick EM et al (2005) Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci 60A:324–333

  41. Vural P, Degirmencioglu S, Parildar-Karpuzoglu H, Dogru-Abbasoglu S, Hanagasi HA, Karadag B, Gurvit H et al (2009) The combinations of TNFalpha-308 and IL-6 -174 or IL-10 -1082 genes polymorphisms suggest an association with susceptibility to sporadic late-onset Alzheimer's disease. Acta Neurol Scand 120:396–401

  42. Webb GR, Westacott CI, Elson CJ (1998) Osteoarthritic synovial fluid and synovium supernatants up-regulate tumor necrosis factor receptors on human articular chondrocytes. Osteoarthr Cartil 6:167–176

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This study was financed by FAPEMIG, CNPq, and supported by the Pro-Rectory for Research of the UFMG. D.S. Pereira was a grant holder of the Coordination of Improvement of Upper Level Staff [Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)] during his Ph.D.

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Correspondence to Leani Souza Máximo Pereira.

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Pereira, D.S., Mateo, E.C.C., de Queiroz, B.Z. et al. TNF-α, IL6, and IL10 polymorphisms and the effect of physical exercise on inflammatory parameters and physical performance in elderly women. AGE 35, 2455–2463 (2013). https://doi.org/10.1007/s11357-013-9515-1

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  • Polymorphism
  • Cytokines
  • Physical exercise
  • Elderly