Skip to main content
SpringerLink
Log in

Physical Function and Strength in Relation to Inflammation in Older Adults with Obesity and Increased Cardiometabolic Risk

  • Published:
The journal of nutrition, health & aging

Abstract

Background

Inflammation is implicated in functional decline and the development of disability in aging. This study aimed to investigate the association of inflammation with physical function and muscle strength in older adults with obesity and increased cardiometabolic risk.

Design

In baseline assessments from the CROSSROADS randomized controlled trial, serum interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and C-reactive protein (hs-CRP) were assayed in 163 older adults (37% males, 24% African American, BMI 34±3, age 70±5yrs) with hypertension, dyslipidemia and/or diabetes. Physical function was assessed by sixminute walk test (6MWT), chair sit-and-reach (CSR), hand-grip and knee-extension strength; specific-strength as muscle strength/mass ratio. Analyses included ANCOVA and multiple linear regression adjusted for thigh skeletal muscle (MRI), arm lean mass (DXA) and moderate-to-vigorous intensity physical activity (MVPA; accelerometry).

Results

Higher hs-CRP (p<0.01) and IL-6 (p=0.07) were associated with lower 6MWT and CSR, respectively. A composite inflammation score combining all 3 inflammatory markers showed the strongest inverse association with 6MWT (p<0.01). MVPA moderated associations such that amongst participants who engaged in low MVPA, 6MWT distances and CSR scores were significantly lower in those with high IL-6 and TNFα (p<0.05), respectively. In participants with high MVPA, higher hs-CRP (p<0.05) and TNFα (p=0.07) were associated with poorer upper-extremity specific-strength.

Conclusions

Chronic inflammation was associated with poorer physical function and specific strength in older adults with obesity and increased cardiometabolic risk. This association was strongest in participants with multiple elevated inflammatory markers. Physical activity levels below current recommendations mitigated the deleterious effects of inflammation on lower body mobility, underscoring the benefits of exercise for preserving physical function with age.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1

Similar content being viewed by others

References

  1. Alvarez-Rodriguez L, Lopez-Hoyos M, Munoz-Cacho P, Martinez-Taboada VM. Aging is associated with circulating cytokine dysregulation. Cell Immunol. 2012;273(2):124–32. Epub 2012/02/10. doi: https://doi.org/10.1016/j.cellimm.2012.01.001. PubMed PMID: 22316526.

    Article  CAS  PubMed  Google Scholar 

  2. Pawelec G, Goldeck D, Derhovanessian E. Inflammation, ageing and chronic disease. Curr Opin Immunol. 2014;29:23–8. Epub 2014/04/26. doi: https://doi.org/10.1016/j.coi.2014.03.007. PubMed PMID: 24762450.

    Article  CAS  PubMed  Google Scholar 

  3. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444(7121):860–7. Epub 2006/12/15. doi: https://doi.org/10.1038/nature05485. PubMed PMID: 17167474.

    Article  CAS  PubMed  Google Scholar 

  4. Fried LP, Guralnik JM. Disability in older adults: evidence regarding significance, etiology, and risk. J Am Geriatr Soc. 1997;45(1):92–100. Epub 1997/01/01. PubMed PMID: 8994496.

    Article  CAS  PubMed  Google Scholar 

  5. Dutta C, Hadley EC. The significance of sarcopenia in old age. J Gerontol A Biol Sci Med Sci. 1995;50 Spec No:1–4. Epub 1995/11/01. PubMed PMID: 7493199.

    Article  PubMed  Google Scholar 

  6. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:139239. Epub 2014/01/24. doi: https://doi.org/10.1155/2013/139239. PubMed PMID: 24455420; PubMed Central PMCID: PMCPMC3881510.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Rall LC, Rosen CJ, Dolnikowski G, et al. Protein metabolism in rheumatoid arthritis and aging. Effects of muscle strength training and tumor necrosis factor alpha. Arthritis Rheum. 1996;39(7):1115–24. Epub 1996/07/01. PubMed PMID: 8670319.

    Article  CAS  PubMed  Google Scholar 

  8. Haddad F, Zaldivar F, Cooper DM, Adams GR. IL-6-induced skeletal muscle atrophy. J Appl Physiol (1985). 2005;98(3):911–7. Epub 2004/11/16. doi: https://doi.org/10.1152/japplphysiol.01026.2004. PubMed PMID: 15542570.

    Article  CAS  Google Scholar 

  9. Roubenoff R. Sarcopenic obesity: the confluence of two epidemics. Obes Res. 2004;12(6):887–8. doi: https://doi.org/10.1038/oby.2004.107. PubMed PMID: 15229325.

    Article  PubMed  Google Scholar 

  10. Villareal DT, Banks M, Siener C, Sinacore DR, Klein S. Physical frailty and body composition in obese elderly men and women. Obes Res. 2004;12(6):913–20. Epub 2004/07/02. doi: https://doi.org/10.1038/oby.2004.111. PubMed PMID: 15229329.

    Article  PubMed  Google Scholar 

  11. Newman AB, Haggerty CL, Goodpaster B, et al. Strength and muscle quality in a well-functioning cohort of older adults: the Health, Aging and Body Composition Study. J Am Geriatr Soc. 2003;51(3):323–30. Epub 2003/02/18. PubMed PMID: 12588575.

    Article  PubMed  Google Scholar 

  12. Ferrucci L, Harris TB, Guralnik JM, et al. Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc. 1999;47(6):639–46. Epub 1999/06/12. PubMed PMID: 10366160.

    Article  CAS  PubMed  Google Scholar 

  13. 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: MacArthur studies of successful aging. J Gerontol A Biol Sci Med Sci. 2000;55(12):M709–15. Epub 2000/12/29. PubMed PMID: 11129392.

    Article  CAS  PubMed  Google Scholar 

  14. Penninx BW, Kritchevsky SB, Newman AB, et al. Inflammatory markers and incident mobility limitation in the elderly. J Am Geriatr Soc. 2004;52(7):1105–13. Epub 2004/06/24. doi: https://doi.org/10.1111/j.1532-5415.2004.52308.x. PubMed PMID: 15209648.

    Article  PubMed  Google Scholar 

  15. Brinkley TE, Leng X, Miller ME, et al. Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci. 2009;64(4):455–61. Epub 2009/02/07. doi: https://doi.org/10.1093/gerona/gln038. PubMed PMID: 19196644; PubMed Central PMCID: PMCPMC2657165.

    Article  PubMed  Google Scholar 

  16. Visser M, Pahor M, Taaffe DR, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57(5):M326–32. PubMed PMID: 11983728.

    Article  PubMed  Google Scholar 

  17. Hollmann W, Struder HK, Tagarakis CV, King G. Physical activity and the elderly. Eur J Cardiovasc Prev Rehabil. 2007;14(6):730–9. Epub 2007/11/29. doi: https://doi.org/10.1097/HJR.0b013e32828622f9. PubMed PMID: 18043292.

    Article  PubMed  Google Scholar 

  18. Simpson RJ, Lowder TW, Spielmann G, Bigley AB, LaVoy EC, Kunz H. Exercise and the aging immune system. Ageing Res Rev. 2012;11(3):404–20. Epub 2012/04/03. doi: https://doi.org/10.1016/j.arr.2012.03.003. PubMed PMID: 22465452.

    Article  CAS  PubMed  Google Scholar 

  19. Gleeson M. Immune function in sport and exercise. J Appl Physiol (1985). 2007;103(2):693–9. Epub 2007/02/17. doi: https://doi.org/10.1152/japplphysiol.00008.2007. PubMed PMID: 17303714.

    Article  CAS  Google Scholar 

  20. Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008;454(7203):463–9. Epub 2008/07/25. doi: https://doi.org/10.1038/nature07206. PubMed PMID: 18650917; PubMed Central PMCID: PMCPMC2587487.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ard JD, Gower B, Hunter G, et al. Effects of Calorie Restriction in Obese Older Adults: The CROSSROADS Randomized Controlled Trial. J Gerontol A Biol Sci Med Sci. 2016. doi: https://doi.org/10.1093/gerona/glw237. PubMed PMID: 28003374.

    Google Scholar 

  22. Haas MC, Bodner EV, Brown CJ, et al. Calorie restriction in overweight seniors: response of older adults to a dieting study: the CROSSROADS randomized controlled clinical trial. J Nutr Gerontol Geriatr. 2014;33(4):376–400. Epub 2014/11/27. doi: https://doi.org/10.1080/21551197.2014.965993. PubMed PMID: 25424512; PubMed Central PMCID: PMCPMC4248142.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Tziakas DN, Chalikias GK, Kaski JC, et al. Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach. Atherosclerosis. 2007;193(1):196–203. Epub 2006/07/22. doi: https://doi.org/10.1016/j.atherosclerosis.2006.06.016. PubMed PMID: 16857204.

    Article  CAS  PubMed  Google Scholar 

  24. Freedson PS, Melanson E, Sirard J. Calibration of the Computer Science and Applications, Inc. accelerometer. Medicine and science in sports and exercise. 1998;30(5):777–81. Epub 1998/05/20. PubMed PMID: 9588623.

    Article  CAS  PubMed  Google Scholar 

  25. A. T. S. Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. American journal of respiratory and critical care medicine. 2002;166(1):111–7. Epub 2002/07/02. doi: https://doi.org/10.1164/ajrccm.166.1.at1102. PubMed PMID: 12091180.

    Article  Google Scholar 

  26. Solway S, Brooks D, Lacasse Y, Thomas S. A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest. 2001;119(1):256–70. Epub 2001/02/07. PubMed PMID: 11157613.

    Article  CAS  PubMed  Google Scholar 

  27. Jones CJ, Rikli RE, Max J, Noffal G. The reliability and validity of a chair sit-and-reach test as a measure of hamstring flexibility in older adults. Res Q Exerc Sport. 1998;69(4):338–43. Epub 1998/12/29. doi: https://doi.org/10.1080/02701367.1998.10607708. PubMed PMID: 9864752.

    Article  CAS  PubMed  Google Scholar 

  28. Guralnik JM, Ferrucci L, Pieper CF, et al. Lower extremity function and subsequent disability: consistency across studies, predictive models, and value of gait speed alone compared with the short physical performance battery. J Gerontol A Biol Sci Med Sci. 2000;55(4):M221–31. Epub 2000/05/16. PubMed PMID: 10811152.

    Article  CAS  PubMed  Google Scholar 

  29. Preacher KJ, Curran PJ, Bauer DJ. Computational tools for probing interaction effects in multiple linear regression, multilevel modeling, and latent curve analysis. Journal of Educational and Behavioural Statistics. 2006;31:437–48.

    Article  Google Scholar 

  30. Studenski SA, Peters KW, Alley DE, et al. The FNIH sarcopenia project: rationale, study description, conference recommendations, and final estimates. J Gerontol A Biol Sci Med Sci. 2014;69(5):547–58. Epub 2014/04/17. doi: https://doi.org/10.1093/gerona/glu010. PubMed PMID: 24737557; PubMed Central PMCID: PMCPMC3991146.

    Article  PubMed  PubMed Central  Google Scholar 

  31. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018;41(Suppl 1):S13–S27. Epub 2017/12/10. doi: https://doi.org/10.2337/dc18-S002. PubMed PMID: 29222373.

    Article  Google Scholar 

  32. Enright PL, Sherrill DL. Reference equations for the six-minute walk in healthy adults. American journal of respiratory and critical care medicine. 1998;158(5 Pt 1):1384–7. Epub 1998/11/17. doi: https://doi.org/10.1164/ajrccm.158.5.9710086. PubMed PMID: 9817683.

    Article  CAS  PubMed  Google Scholar 

  33. World Health Organization. Global Recommendations on Physical Activity for Health. Geneva, Switzerland: World Health Organization; 2010.

    Google Scholar 

  34. Nelson ME, Rejeski WJ, Blair SN, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Medicine and science in sports and exercise. 2007;39(8):1435–45. Epub 2007/09/01. doi: https://doi.org/10.1249/mss.0b013e3180616aa2. PubMed PMID: 17762378.

    Article  PubMed  Google Scholar 

  35. Nicklas BJ. No Expiration Date on the Association Between Physical Activity and Mortality. J Am Geriatr Soc. 2018;66(5):850–2. Epub 2018/01/11. doi: https://doi.org/10.1111/jgs.15243. PubMed PMID: 29319876.

    Article  PubMed  Google Scholar 

  36. LaMonte MJ, Buchner DM, Rillamas-Sun E, et al. Accelerometer-Measured Physical Activity and Mortality in Women Aged 63 to 99. J Am Geriatr Soc. 2018;66(5):886–94. Epub 2017/11/17. doi: https://doi.org/10.1111/jgs.15201. PubMed PMID: 29143320; PubMed Central PMCID: PMCPMC5955801.

    Article  PubMed  Google Scholar 

  37. Messier SP, Mihalko SL, Legault C, et al. Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: the IDEA randomized clinical trial. JAMA. 2013;310(12):1263–73. doi: https://doi.org/10.1001/jama.2013.277669. PubMed PMID: 24065013; PubMed Central PMCID: PMCPMC4450354.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Stenholm S, Koster A, Valkeinen H, et al. Association of Physical Activity History With Physical Function and Mortality in Old Age. J Gerontol A Biol Sci Med Sci. 2016;71(4):496–501. Epub 2015/08/21. doi: https://doi.org/10.1093/gerona/glv111. PubMed PMID: 26290538; PubMed Central PMCID: PMCPMC4834834.

    Article  PubMed  Google Scholar 

  39. Bouaziz W, Vogel T, Schmitt E, Kaltenbach G, Geny B, Lang PO. Health benefits of aerobic training programs in adults aged 70 and over: a systematic review. Arch Gerontol Geriatr. 2017;69:110–27. Epub 2016/12/03. doi: https://doi.org/10.1016/j.archger.2016.10.012. PubMed PMID: 27912156.

    Article  PubMed  Google Scholar 

  40. Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation. 2007;116(19):2110–8. Epub 2007/10/31. doi: https://doi.org/10.1161/CIRCULATIONAHA.107.729939. PubMed PMID: 17967770; PubMed Central PMCID: PMCPMC2117381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Boekholdt SM, Stroes ES. The interleukin-6 pathway and atherosclerosis. Lancet. 2012;379(9822):1176–8. Epub 2012/03/17. doi: https://doi.org/10.1016/S0140-6736(12)60361-4. PubMed PMID: 22421338.

    Article  PubMed  Google Scholar 

  42. Interleukin-6 Receptor Mendelian Randomisation Analysis Consortium, Swerdlow DI, Holmes MV, et al. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet. 2012;379(9822):1214–24. Epub 2012/03/17. doi: https://doi.org/10.1016/S0140-6736(12)60110-X. PubMed PMID: 22421340; PubMed Central PMCID: PMCPMC3316968.

    Article  CAS  Google Scholar 

  43. Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training on chronic inflammation. Clin Chim Acta. 2010;411(11–12):785–93. Epub 2010/03/02. doi: https://doi.org/10.1016/j.cca.2010.02.069. PubMed PMID: 20188719; PubMed Central PMCID: PMCPMC3629815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cesari M, Penninx BW, Newman AB, et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation. 2003;108(19):2317–22. Epub 2003/10/22. doi: https://doi.org/10.1161/01.CIR.0000097109.90783. FC. PubMed PMID: 14568895.

    Article  CAS  PubMed  Google Scholar 

  45. Munoz-Canoves P, Scheele C, Pedersen BK, Serrano AL. Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? FEBS J. 2013;280(17):4131–48. Epub 2013/05/15. doi: https://doi.org/10.1111/febs.12338. PubMed PMID: 23663276; PubMed Central PMCID: PMCPMC4163639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Steensberg A, Febbraio MA, Osada T, et al. Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. J Physiol. 2001;537(Pt 2):633–9. Epub 2001/12/04. PubMed PMID: 11731593; PubMed Central PMCID: PMCPMC2278951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lambert CP, Wright NR, Finck BN, Villareal DT. Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons. J Appl Physiol (1985). 2008;105(2):473–8. Epub 2008/06/07. doi: https://doi.org/10.1152/japplphysiol.00006.2008. PubMed PMID: 18535122; PubMed Central PMCID: PMCPMC2519937.

    Article  CAS  Google Scholar 

  48. Greiwe JS, Cheng B, Rubin DC, Yarasheski KE, Semenkovich CF. Resistance exercise decreases skeletal muscle tumor necrosis factor alpha in frail elderly humans. FASEB J. 2001;15(2):475–82. Epub 2001/02/07. doi: https://doi.org/10.1096/fj.00-0274com. PubMed PMID: 11156963.

    Article  CAS  PubMed  Google Scholar 

  49. Beavers KM, Ambrosius WT, Nicklas BJ, Rejeski WJ. Independent and combined effects of physical activity and weight loss on inflammatory biomarkers in overweight and obese older adults. J Am Geriatr Soc. 2013;61(7):1089–94. doi: https://doi.org/10.1111/jgs.12321. PubMed PMID: 23772804; PubMed Central PMCID: PMCPMC3714323.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Villareal DT, Aguirre L, Gurney AB, et al. Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults. N Engl J Med. 2017;376(20):1943–55. Epub 2017/05/18. doi: https://doi.org/10.1056/NEJMoa1616338. PubMed PMID: 28514618; PubMed Central PMCID: PMCPMC5552187.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors thank the volunteers for their participation and gratefully acknowledge the staff of the UAB Metabolism Core Laboratory (Nutrition Obesity Research Center, Diabetes Research and Training Center, Center for Clinical and Translational Science) for their involvement in this study.

Funding

Funding: This study was supported by the National Institute on Aging at the National Institutes of Health (R01 AG033094), UAB Nutrition Obesity Research Center (P30 DK56336) and Diabetes Research Center (P30DK079626). JT was supported by a postgraduate research scholarship from the Agency for Science, Technology and Research (A-STAR), Singapore. JLL and JT were supported by a Career Academic Leadership Award from NIA (K07 AG043588). Funding sources had no role in the design, conduct, or reporting of the study or the decision to submit the manuscript for publication.

Author information

Authors and Affiliations

  1. Department of Nutrition Sciences, University of Alabama at Birmingham, 514 Webb Building, 1675 University Blvd, Birmingham, AL, 35294-3360, USA

    Jeannie Tay, A. M. Goss & B. A. Gower

  2. Singapore Institute of Clinical Sciences (SICS), Agency for Science, Technology and Research (A-STAR), Singapore, Singapore

    Jeannie Tay

  3. Division of Gerontology, Geriatrics, and Palliative Care, UAB, Birmingham, Alabama, USA

    J. L. Locher

  4. Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA

    J. D. Ard

Authors
  1. Jeannie Tay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. M. Goss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. L. Locher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. D. Ard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. A. Gower
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Author Contributions: JT and BAG had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: All authors. Analysis and interpretation of data: JT and BAG. Drafting of the manuscript: JT and BAG. Critical revision the manuscript for intellectual content: All authors. Read and approved the final manuscript: All authors. Obtained funding: JLL, JDA and BAG.

Corresponding author

Correspondence to Jeannie Tay.

Ethics declarations

Conflict of interest: The authors declared no conflicts of interest.

Ethical Standards: The University of Alabama at Birmingham Institutional Review Board approved the study and all participants provided written informed consent.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tay, J., Goss, A.M., Locher, J.L. et al. Physical Function and Strength in Relation to Inflammation in Older Adults with Obesity and Increased Cardiometabolic Risk. J Nutr Health Aging 23, 949–957 (2019). https://doi.org/10.1007/s12603-019-1260-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12603-019-1260-4

Key words

Search

Navigation