Association of fatigue, inflammation, and physical activity on gait speed: the Long Life Family Study

LLFS Research Group

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Background: Fatigue, inflammation, and physical activity (PA) are all independently associated with gait speed, but their directionality is not fully elucidated. Aims: Evaluate the bidirectional associations amongst fatigue, inflammation, and PA on gait speed. Methods: This cross sectional study included probands (n = 1280, aged 49–105) and offspring (n = 2772, aged 24–88) in the Long Life Family Study. We assessed gait speed, fatigue with the question “I could not get going”, inflammation using fasting interleukin-6 (IL-6) and high sensitivity C-reactive protein (CRP), and self-reported PA as walking frequency in the past two weeks. The two generations were examined separately using linear mixed modeling. Results: Lower fatigue, lower IL-6, and greater PA were all associated with faster gait speed in both generations (all p < 0.05); lower CRP was only associated with faster gait speed in the offspring. PA explained the association of fatigue and gait speed via a 16.1% (95% CI 9.7%, 26.7%) attenuation of the direct associations for the probands and 9.9% (95% CI 6.3%, 18.8%) in the offspring. In addition, IL-6 explained more of the association of fatigue and gait speed than the association between PA and gait speed, via a 14.9% (95% CI 9.2%, 23.4%) attenuation of the direct association in the offspring only. Discussion: Results revealed a potential directionality from fatigue to IL-6 to PA that may lead to faster gait speed. Future work should examine these relationships longitudinally to establish temporality and causality. Conclusions: Our findings support a signal that lowering fatigue and inflammation and increasing physical activity may delay functional decline.

Original languageEnglish
JournalAging Clinical and Experimental Research
Issue number2
Pages (from-to)367-374
Publication statusPublished - Feb 2022


  • Fatigability
  • Inflammatory markers
  • Lifespan
  • Mobility
  • Physical function
  • Cross-Sectional Studies
  • Gait
  • Humans
  • Fatigue
  • Inflammation
  • Exercise
  • Aged, 80 and over
  • Aged
  • Walking Speed


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