Longitudinal Association Between Energy Regulation and Fatigability in Mid-to-Late Life

Background: Deficits in energy production and utilization have been linked to higher fatigue and functional decline with aging. Lesser known is whether individuals with a combination of low peak energy capacity and high energy costs for mobility (eg, impaired energy regulation) are more likely to experience the onset and progression of high fatigability with aging. Methods: Participants in the Baltimore Longitudinal Study of Aging (n = 651, 49.0% male, mean age 71.9, range 50-94) with >= 2 visits who completed fatigability (Borg rating of perceived exertion [RPE] after a 5-minute 1.5 mph treadmill walk), slow walking energy expenditure (VO2 mL/kg/min), and peak walking energy expenditure (VO2 mL/kg/min), testing between 2007 and 2018. The longitudinal association between each measure of energy expenditure, a ratio of energy cost-to-capacity (cost ratio), and perceived fatigability was modeled using mixed effects models adjusted for age, body composition, and comorbidities. Time to higher perceived fatigability (RPE >= 10) was modeled using Cox proportional hazards models. Results: In continuous analyses, higher slow walking energy expenditure (p < .05) and a higher cost ratio (p <= .001) were associated with greater perceived fatigability over time. Cox proportional hazards models using tertiles of the cost ratio suggest that, compared to those in the lowest tertile, those in the middle and highest tertiles had 1.89 (95% confidence interval [CI]: 1.57-5.16) and 2.85 (95% CI: 1.05-3.40) times greater risk of developing higher fatigability, respectively. Conclusion: Findings suggest that strategies to prevent fatigability should consider methods to improve energy regulation by targeting both the independent and combined effects of declining peak capacity and rising energy costs for mobility with aging.