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

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

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Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Center on Aging and Health, Johns Hopkins University and Medical Institutions, Baltimore, Maryland.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Intramural Research Program, National Institute on Aging, Baltimore, Maryland.



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.


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.


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).


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.


Aging; Chronic inflammation; Fatigue; IL-6; Inflammaging; Older adults

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