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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. [ABSTRACT FROM AUTHOR]

Background: With aging, daily physical activity (PA) becomes less frequent and more fragmented. Accumulation patterns of daily PA-including transitions from active-to-sedentary behaviors-may provide important insights into functional status in older, less active populations.Methods: Participants of the Baltimore Longitudinal Study of Aging (n = 680, 50% male, aged 27-94 years) completed a clinical assessment and wore an Actiheart accelerometer. Transitions between active and sedentary states were modeled as a probability (Active-to-Sedentary Transition Probability [ASTP]) defined as the reciprocal of the average PA bout duration. Cross-sectional associations between ASTP and gait speed (m/s), fatigability (rating-of-perceived-exertion [RPE]), 400 m time (seconds), and expanded short physical performance battery score were modeled using linear and logistic regression, adjusted for chronic conditions. Further analyses explored the utility of ASTP over-and-above total daily PA.Results: In continuous models, each 0.10-unit higher ASTP was associated slower gait (β = -0.06 m/s, SE = 0.01), higher fatigability (β = 0.60 RPE, SE = 0.12), slower 400 m time (β = 16.31 s, SE = 2.70), and lower functioning (β = -0.13 expanded short physical performance battery score, SE = 0.03; p < .001). In categorical analyses, those in the highest tertile of ASTP were >2 times more likely to have high fatigability (rating of perceived exertion ≥10), slow 400 m time (>300 seconds) and reduced functional performance (expanded short physical performance battery score < 3.07) than those in the lowest tertile (p < .01). Further analyses demonstrated ASTP provided additional insight into functional outcomes beyond total daily PA.Conclusion: Fragmented daily PA-as measured by ASTP-is strongly linked with measures of health and functional status and may identify those at risk of high fatigability and reduced functional performance over and above traditional PA metrics. [ABSTRACT FROM AUTHOR]