TY - JOUR
T1 - Longitudinal relationship between interleukin-6 and perceived fatigability among well-functioning adults in mid-to-late life
AU - Wanigatunga, Amal A.
AU - Varadhan, Ravi
AU - Simonsick, Eleanor M.
AU - Carlson, Olga D.
AU - Studenski, Stephanie
AU - Ferrucci, Luigi
AU - Schrack, Jennifer A.
N1 - Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - Aging
KW - Chronic inflammation
KW - Fatigue
KW - IL-6
KW - Inflammaging
KW - Older adults
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U2 - 10.1093/gerona/gly120
DO - 10.1093/gerona/gly120
M3 - Article
C2 - 29846512
AN - SCOPUS:85066915850
SN - 1079-5006
VL - 74
SP - 720
EP - 725
JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
IS - 5
ER -