The Impact of Resistance Training on IL-6, TNF-a, and CRP Levels in the Elderly: A Systematic Review and Meta-Analysis Study
Keywords:
Exercise, Aging, Inflammation, Geriatrics, Randomized Controlled TrialsAbstract
Background: Inflammatory markers have been linked to an increased risk of cardiovascular diseases including atherosclerosis, coronary artery disease, and heart failure in the elderly individuals. Resistance exercises are one effective method to manage inflammation in this population. Objectives: This meta-analysis aimed to explore the impact of resistance training on inflammatory markers in the elderly. Methods: All randomized controlled clinical trials (from 2004 to 2023) that examined the effect of resistance training on tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and C-reactive protein (CRP) in individuals over 50 years old were selected through a systematic search of PubMed, Google Scholar, Web of Science and SID databases, that out of 600 studies identified, 31 met the inclusion criteria for our analysis. Random and fixed effects models, along with the I2 heterogeneity test, Egger test, and funnel plot, were used to determine publication bias using CMA2 software. The effect size (ES) was reported in terms of the standard mean difference (SMD) and a 95% confidence interval (CI). Results: The meta-analysis results indicated that resistance training significantly reduced CRP (ES = -0.49, 95% CI = -0.34 to -0.64, P = 0.001) and IL-6 (ES = -0.27, 95% CI = -0.41 to -0.13, P = 0.001) levels. However, it did not have a significant effect on TNF-α levels (ES = -0.22, 95% CI = 0.02 to -0.47, P = 0.075). Subgroup analyses revealed that resistance training for more than 16 weeks and a training frequency of three times a week led to a greater decrease in CRP and IL-6 levels in the elderly. <b>Conclusions:</b> The findings of this meta-analysis suggest a significant decrease in CRP and IL-6 levels in the elderly due to resistance training. Furthermore, the subgroup analysis indicated that higher training volumes (training duration and frequency) result in a greater reduction in these markers' levels. Based on these findings, it is advisable for elderly individuals to consider incorporating resistance training into their regular exercise routines.
Downloads
References
1. WHO. Ageing and health. World Health Organization; 2022. Available
from: https://www.who.int/news-room/fact-sheets/detail/ageingand-health.
2. Masoro EJ. Handbook of physiology: Section 11: Aging. New York (NY):
Oxford University Press; 1995.
3. Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, Minson CT, Nigg
CR, Salem GJ, et al. Exercise and physical activity for older adults. Med
Sci Sports Exerc. 2009;41(7):1510–30. [PubMed ID: 19516148]. https://doi.
org/10.1249/MSS.0b013e3181a0c95c.
4. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M,
Ottaviani E, et al. Inflamm-aging. An evolutionary perspective
on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.
[PubMed ID: 10911963]. https://doi.org/10.1111/j.1749-6632.2000.
tb06651.x.
5. Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training
on chronic inflammation. Clin Chim Acta. 2010;411(11-12):785–93.
[PubMed ID: 20188719]. [PubMed Central ID: PMC3629815]. https://doi.
org/10.1016/j.cca.2010.02.069.
6. Briasoulis A, Androulakis E, Christophides T, Tousoulis D. The role
of inflammation and cell death in the pathogenesis, progression
and treatment of heart failure. Heart Fail Rev. 2016;21(2):169–76.
[PubMed ID: 26872673]. https://doi.org/10.1007/s10741-016-9533-z.
7. Dick SA, Epelman S. Chronic heart failure and inflammation: What do
we really know? Circ Res. 2016;119(1):159–76. [PubMed ID: 27340274].
https://doi.org/10.1161/CIRCRESAHA.116.308030.
8. Van Linthout S, Tschope C. Inflammation - cause or consequence
of heart failure or both? Curr Heart Fail Rep. 2017;14(4):251–65.
[PubMed ID: 28667492]. [PubMed Central ID: PMC5527060]. https://
doi.org/10.1007/s11897-017-0337-9.
9. Alexander WS. Suppressors of cytokine signalling (SOCS)
in the immune system. Nat Rev Immunol. 2002;2(6):410–6.
[PubMed ID: 12093007]. https://doi.org/10.1038/nri818.
10. Janeway C, Murphy KP, Travers P, Walport M. Janeway’s immuno
biology. Garland Science; 2008.
11. McFarlin BK, Flynn MG, Campbell WW, Craig BA, Robinson JP,
Stewart LK, 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(4):388–93. [PubMed ID: 16611706]. https://doi.org/10.
1093/gerona/61.4.388.
12. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in
the elderly. Exp Gerontol. 2004;39(5):687–99. [PubMed ID: 15130663].
https://doi.org/10.1016/j.exger.2004.01.009.
13. Blake GJ, Ridker PM. Novel clinical markers of vascular wall
inflammation. Circ Res. 2001;89(9):763–71. [PubMed ID: 11679405].
https://doi.org/10.1161/hh2101.099270.
14. Hotamisligil GS. Inflammation and metabolic disorders. Nature.
2006;444(7121):860–7. [PubMed ID: 17167474]. https://doi.org/10.1038/
nature05485.
15. Hunter GR, McCarthy JP, Bamman MM. Effects of resistance training
on older adults. Sports Med. 2004;34(5):329–48. [PubMed ID: 15107011].
https://doi.org/10.2165/00007256-200434050-00005.
16. Golpasasndi S, Abdollahpour S, Golpasandi H. High-intensity interval
training combined with saffron supplementation modulates
stress-inflammatory markers in obese women with type 2 diabetes.
Res Exerc Nutr. 2022;1(1):61–55. https://doi.org/10.34785/j019.2022.002.
17. Pate RR, Pratt M, Blair SN, Haskell WL, Macera CA, Bouchard C, et
al. Physical activity and public health. A recommendation from the
Centers for Disease Control and Prevention and the American College
of Sports Medicine. JAMA. 1995;273(5):402–7. [PubMed ID: 7823386].
https://doi.org/10.1001/jama.273.5.402.
18. Azali Alamdari K, SatarZadeh R. Impact of aerobic training and
vitamin D supplementation on hunger rate and serum ghrelin and
insulin in middle agead females with metablic syndrome. Res Exerc
Nutr. 2022;1(1):13–1. Persian. https://doi.org/10.34785/j019.2022.408.
19. Black AE, Coward WA, Cole TJ, Prentice AM. Human energy
expenditure in affluent societies: an analysis of 574 doubly-labelled
water measurements. Eur J Clin Nutr. 1996;50(2):72–92.
[PubMed ID: 8641250].
20. Westerterp KR, Meijer EP. Physical activity and parameters of aging:
A physiological perspective. J Gerontol A Biol Sci Med Sci. 2001;56
Spec No 2:7–12. [PubMed ID: 11730240].https://doi.org/10.1093/gerona/
56.suppl 2.7.
21. Brooks N, Layne JE, Gordon PL, Roubenoff R, Nelson ME,
Castaneda-Sceppa C. Strength training improves muscle quality
and insulin sensitivity in Hispanic older adults with type 2 diabetes.
Int J Med Sci. 2006;4(1):19–27. [PubMed ID: 17211497]. [PubMed Central
ID: PMC1752232]. https://doi.org/10.7150/ijms.4.19.
22. Deibert P, Solleder F, Konig D, Vitolins MZ, Dickhuth HH, Gollhofer A,
et al. Soy protein based supplementation supports metabolic effects
of resistance training in previously untrained middle aged males.
Aging Male. 2011;14(4):273–9. [PubMed ID: 22066824]. https://doi.org/
10.3109/13685538.2011.565091.
23. Hagstrom AD, Marshall PW, Lonsdale C, Papalia S, Cheema BS,
Toben C, et al. The effect of resistance training on markers of
immune function and inflammation in previously sedentary women
recovering from breast cancer: a randomized controlled trial. Breast
Cancer Res Treat. 2016;155(3):471–82. [PubMed ID: 26820653]. https://
doi.org/10.1007/s10549-016-3688-0.
24. Karabulut M, Sherk VD, Bemben DA, Bemben MG. Inflammation
marker, damage marker and anabolic hormone responses to
resistance training with vascular restriction in older males. Clin
Physiol Funct Imaging. 2013;33(5):393–9. [PubMed ID: 23701309].
https://doi.org/10.1111/cpf.12044.
25. Mavros Y, Kay S, Simpson KA, Baker MK, Wang Y, Zhao RR, et
al. Reductions in C-reactive protein in older adults with type 2
diabetes are related to improvements in body composition following
a randomized controlled trial of resistance training. J Cachexia
Sarcopenia Muscle. 2014;5(2):111–20. [PubMed ID: 24687180]. [PubMed
Central ID: PMC4053559]. https://doi.org/10.1007/s13539-014-0134-1.
26. Ogawa K, Sanada K, Machida S, Okutsu M, Suzuki K. Resistance
exercise training-induced muscle hypertrophy was associated with
reduction of inflammatory markers in elderly women. Mediators
Inflamm. 2010;2010:171023. [PubMed ID: 21253481]. [PubMed Central
ID: PMC3022197]. https://doi.org/10.1155/2010/171023.
27. Faraji H, Mmirahmad F, Mahammadi A. The effect of strawberry
extract supplementation on some oxidative, inflammatory and
cellular damage indicators after a session of exhausting resistance
exercise in non-athlete women. Res Exerc Nutr. 2022;1(2):1–10. Persian.
https://doi.org/10.34785/j019.2023.001.
28. Abd El-Kader SM, Al-Shreef FM, Al-Jiffri OH. Impact of aerobic
exercise versus resisted exercise on endothelial activation
markers and inflammatory cytokines among elderly. Afr Health
Sci. 2019;19(4):2874–80. [PubMed ID: 32127863]. [PubMed Central ID:
PMC7040351]. https://doi.org/10.4314/ahs.v19i4.9.
29. Chupel MU, Direito F, Furtado GE, Minuzzi LG, Pedrosa FM, Colado
JC, et al. Strength training decreases inflammation and increases
cognition and physical fitness in older women with cognitive
impairment. Front Physiol. 2017;8:377. [PubMed ID: 28659812].
[PubMed Central ID: PMC5467003]. https://doi.org/10.3389/fphys.
2017.00377.
30. Macedo Santiago LA, Neto LGL, Borges Pereira G, Leite RD, Mostarda
CT, de Oliveira Brito Monzani J, et al. Effects of resistance training
on immunoinflammatory response, TNF-alpha gene expression, and
body composition in elderly women. J Aging Res. 2018;2018:1467025.
[PubMed ID: 30510801]. [PubMed Central ID: PMC6230406]. https://
doi.org/10.1155/2018/1467025.
31. Mirseyyedi M, Attarzadeh Hosseini SR, Mir E, Hejazi K. Changes in
C-reactive protein, interleukin-6 and lipid biomarkers in sedentary
middle-aged men after resistance exercise. J Sabzevar Univ Med Sci.
2014;21(2):283–92.
32. Taghian F, Ghatreh Samani K. Dose 12 week resistance training
Influence IL-18 and CRP levels in elderly men? Razi J Med Sci.
2018;24(165):77–84.
33. Tomeleri CM, Ribeiro AS, Souza MF, Schiavoni D, Schoenfeld BJ,
Venturini D, et al. Resistance training improves inflammatory level,
lipid and glycemic profiles in obese older women: A randomized
controlled trial. Exp Gerontol. 2016;84:80–7. [PubMed ID: 27616162].
https://doi.org/10.1016/j.exger.2016.09.005.
34. Bruunsgaard H, Bjerregaard E, Schroll M, Pedersen BK. Muscle
strength after resistance training is inversely correlated with
baseline levels of soluble tumor necrosis factor receptors in the
oldest old. J Am Geriatr Soc. 2004;52(2):237–41. [PubMed ID: 14728633].
https://doi.org/10.1111/j.1532-5415.2004.52061.x.
35. Bautmans I, Lambert M, Mets T. The six-minute walk test in
community dwelling elderly: influence of health status. BMC Geriatr.
2004;4:6. [PubMed ID: 15272934]. [PubMed Central ID: PMC512286].
https://doi.org/10.1186/1471-2318-4-6.
36. Reynolds JL, Ignatowski TA, Sud R, Spengler RN. Brain-derived
tumor necrosis factor-alpha and its involvement in noradrenergic
neuron functioning involved in the mechanism of action of
an antidepressant. J Pharmacol Exp Ther. 2004;310(3):1216–25.
[PubMed ID: 15082752]. https://doi.org/10.1124/jpet.104.067835.
37. Martins RA, Verissimo MT, Coelho e Silva MJ, Cumming SP,
Teixeira AM. Effects of aerobic and strength-based training on
metabolic health indicators in older adults. Lipids Health Dis.
2010;9:76. [PubMed ID: 20663148]. [PubMed Central ID: PMC2912308].
https://doi.org/10.1186/1476-511X-9-76.
38. Soheyli S, Gaeini A, Souri R. The effects of resistance training on
systemic inflammatory markers in aging men. Olympic Quarterly.
2010;4(48):51–61.
39. Libardi CA, De Souza GV, Cavaglieri CR, Madruga VA,
Chacon-Mikahil MP. Effect of resistance, endurance, and concurrent
training on TNF-alpha, IL-6, and CRP. Med Sci Sports Exerc.
2012;44(1):50–6. [PubMed ID: 21697747]. https://doi.org/10.1249/
MSS.0b013e318229d2e9.
40. Stensvold D, Slordahl SA, Wisloff U. Effect of exercise training on
inflammation status among people with metabolic syndrome. Metab
Syndr Relat Disord. 2012;10(4):267–72. [PubMed ID: 22455564]. https://
doi.org/10.1089/met.2011.0140.
41. Feiereisen P, Vaillant M, Gilson G, Delagardelle C. Effects of
different training modalities on circulating anabolic/catabolic
markers in chronic heart failure. J Cardiopulm Rehabil Prev.
2013;33(5):303–8. [PubMed ID: 23959209]. https://doi.org/10.1097/
HCR.0b013e3182a1e4e5.
42. Wanderley FA, Moreira A, Sokhatska O, Palmares C, Moreira P,
Sandercock G, et al. Differential responses of adiposity, inflammation
and autonomic function to aerobic versus resistance training in older
adults. Exp Gerontol. 2013;48(3):326–33. [PubMed ID: 23333772]. https:
//doi.org/10.1016/j.exger.2013.01.002.
43. Rodriguez-Miguelez P, Fernandez-Gonzalo R, Almar M, Mejias Y, Rivas
A, de Paz JA, et al. Role of Toll-like receptor 2 and 4 signaling
pathways on the inflammatory response to resistance training in
elderly subjects. Age (Dordr). 2014;36(6):9734. [PubMed ID: 25427999].
[PubMed Central ID: PMC4245402]. https://doi.org/10.1007/s11357-014-
9734-0.
44. Ribeiro AS, Tomeleri CM, Souza MF, Pina FL, Schoenfeld BJ,
Nascimento MA, et al. Effect of resistance training on C-reactive
protein, blood glucose and lipid profile in older women with
differing levels of RT experience. Age (Dordr). 2015;37(6):109.
[PubMed ID: 26499819]. [PubMed Central ID: PMC5005848].
https://doi.org/10.1007/s11357-015-9849-y.
45. Strandberg E, Edholm P, Ponsot E, Wahlin-Larsson B, Hellmen
E, Nilsson A, et al. Influence of combined resistance training
and healthy diet on muscle mass in healthy elderly women: a
randomized controlled trial. J Appl Physiol (1985). 2015;119(8):918–25.
[PubMed ID: 26338453]. https://doi.org/10.1152/japplphysiol.00066.
2015.
46. Hsieh PL, Tseng CH, Tseng YJ, Yang WS. Resistance training improves
muscle function and cardiometabolic risks but not quality of life in
older people with type 2 diabetes mellitus: A randomized controlled
trial. J Geriatr Phys Ther. 2018;41(2):65–76. [PubMed ID: 27893563].
https://doi.org/10.1519/JPT.0000000000000107.
47. Mehrabani J, Mirmohamadloo F, Nobari H. The Effect of 8 Weeks
of Circuit Resistance Training on Ox-LDL, hs-CRP, HbA1c and Insulin
Resistance Index in Sedentary Postmenopausal Women. Sport Physiol
Manag Investig. 2016;8(4):47–57.
48. Nunes PR, Barcelos LC, Oliveira AA, Furlanetto Junior R, Martins
FM, Orsatti CL, et al. Effect of resistance training on muscular
strength and indicators of abdominal adiposity, metabolic risk,
and inflammation in postmenopausal women: controlled and
randomized clinical trial of efficacy of training volume. Age
(Dordr). 2016;38(2):40. [PubMed ID: 26984105]. [PubMed Central
ID: PMC5005909]. https://doi.org/10.1007/s11357-016-9901-6.
49. Theodorou AA, Panayiotou G, Volaklis KA, Douda HT, Paschalis
V, Nikolaidis MG, et al. Aerobic, resistance and combined
training and detraining on body composition, muscle strength,
lipid profile and inflammation in coronary artery disease
patients. Res Sports Med. 2016;24(3):171–84. [PubMed ID: 27258806].
https://doi.org/10.1080/15438627.2016.1191488.
50. Kabir B, Taghian F, Ghatreh S k. Does 12 weeks of resistance training
effective on the level of interleukin-18 and C-reactive protein in
elderly men? Razi J Med Sci. 2018;24(165):85–92.
51. Tolouei Azar J, saberi Y, ghorbanian B, nourani B. Investigating the
effect of aerobic training and sesamin supplementation on serum
levels of tumor necrosis factor-alpha and C-reactive protein in trained
men. Complement Med J. 2018;8(1):2194–205. Persian.
52. Tomeleri CM, Souza MF, Burini RC, Cavaglieri CR, Ribeiro AS, Antunes
M, et al. Resistance training reduces metabolic syndrome and
inflammatory markers in older women: A randomized controlled
trial. J Diabetes. 2018;10(4):328–37. [PubMed ID: 29031002]. https://doi.
org/10.1111/1753-0407.12614.
53. Nabuco HCG, Tomeleri CM, Fernandes RR, Sugihara Junior
P, Cavalcante EF, Cunha PM, et al. Effect of whey protein
supplementation combined with resistance training on body
composition, muscular strength, functional capacity, and
plasma-metabolism biomarkers in older women with sarcopenic
obesity: A randomized, double-blind, placebo-controlled
trial. Clin Nutr ESPEN. 2019;32:88–95. [PubMed ID: 31221297].
https://doi.org/10.1016/j.clnesp.2019.04.007.
54. Cordova C, Lopes ESF, Pires AS, Souza VC, Brito CJ, Moraes ´
CF, et al. Long-term resistance training is associated with
reduced circulating levels of IL-6, IFN-γ and TNF-α in elderly
women. Neuroimmunomodulation. 2011;18(3):165–70. eng.
[PubMed ID: 21311202]. https://doi.org/10.1159/000323396.
55. Sardeli AV, Tomeleri CM, Cyrino ES, Fernhall B, Cavaglieri CR,
Chacon-Mikahil MPT. Effect of resistance training on inflammatory
markers of older adults: Ameta-analysis. Exp Gerontol. 2018;111:188–96.
[PubMed ID: 30071283]. https://doi.org/10.1016/j.exger.2018.07.021.
56. Peake JM, Kukuljan S, Nowson CA, Sanders K, Daly RM.
Inflammatory cytokine responses to progressive resistance
training and supplementation with fortified milk in men
aged 50+ years: an 18-month randomized controlled trial.
Eur J Appl Physiol. 2011;111(12):3079–88. [PubMed ID: 21455612].
https://doi.org/10.1007/s00421-011-1942-z.
57. Reiss AB, Siegart NM, De Leon J. Interleukin-6 in atherosclerosis:
Atherogenic or atheroprotective? Clin Lipidol. 2017;12(1):14–23. https:
//doi.org/10.1080/17584299.2017.1319787.
58. Fatkhullina AR, Peshkova IO, Koltsova EK. The role of cytokines
in the development of atherosclerosis. Biochemistry (Mosc).
2016;81(11):1358–70. [PubMed ID: 27914461]. [PubMed Central ID:
PMC5471837]. https://doi.org/10.1134/S0006297916110134.
59. Farajzadeh D, Karimi-Gharigh S, Dastmalchi S. Tumor necrosis
factor-alpha and its inhibition strategies: Review article. Tehran Univ
Med J. 2017;75(3):159–71. Persian.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
