Longitudinal Relationship Between Interleukin-6 and Perceived Fatigability Among Well-Functioning Adults in Mid-to-Late Life

J Gerontol A Biol Sci Med Sci. 2019 Apr 23;74(5):720-725. doi: 10.1093/gerona/gly120.


Background: Chronically elevated interleukin-6 (IL-6) levels contribute to fatigue and functional decline via multiple pathways that often lead to frailty. Lesser known is the contribution of IL-6 to fatigue in relation to a standardized workload (fatigability), a precursor to functional decline. Therefore, the purpose of this study was to examine the longitudinal relationship between IL-6 and fatigability.

Methods: About 985 participants from the Baltimore Longitudinal Study of Aging (mean age: 70 ± 10 years) were evaluated every 1-4 years. IL-6 was measured in fasting serum samples at each visit and log-transformed for analyses. Perceived fatigability (PF) was defined as self-reported exertion (rate of perceived exertion; RPE) after a 5-min, 0.67 m/s, 0% grade treadmill walk. Continuous and categorical associations between IL-6 (baseline and repeated measures) and PF were assessed using generalized estimating equations, adjusting for demographics, behavioral factors, and comorbid conditions.

Results: In fully adjusted continuous models, twofold higher baseline IL-6 was associated with a 0.28 higher RPE (p = .03). This relationship tended to remain constant annually (baseline log IL-6 by time interaction p = .29). To provide clinical relevance, the sample median (3.7 pg/mL) was used to examine high versus low IL-6 levels. Over time, the high group reported an average 0.25 higher RPE (p = .03) than the low group. Annual change in logged IL-6 was not associated with annual change in PF (p = .48).

Conclusion: Findings suggest that elevated IL-6 is a biomarker of physiological dysregulation associated with greater fatigability, but there is no longitudinal association between IL-6 and fatigability. Future studies should evaluate whether interventions that aim to reduce inflammation also attenuate fatigability.

Keywords: Aging; Chronic inflammation; Fatigue; IL-6; Inflammaging; Older adults.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Fatigue / blood*
  • Female
  • Geriatric Assessment
  • Humans
  • Interleukin-6 / blood*
  • Longitudinal Studies
  • Male
  • Middle Aged


  • Biomarkers
  • Interleukin-6