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Updated: Jan 27, 2026

The Treadmill Fatigue Test: A Simple, High-throughput Assay of Fatigue-like Behavior for the Mouse
Published on: May 31, 2016
Impact of sarcopenia on diaphragm muscle fatigue
Matthew J Fogarty1, Carlos B Mantilla1,2, Gary C Sieck1,2
1Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
New Findings:
What is the central question of this study? Is the residual force generated by the diaphragm muscle after repeated activation reduced with sarcopenia, and is the residual force generated after fatiguing activation sufficient to sustain ventilatory behaviours of diaphragm muscle in young and old rats? What is the main finding and its importance? After diaphragm muscle fatigue, the residual specific force after 120 s of repeated stimulation was unaffected by ageing and was sufficient to accomplish ventilatory behaviours, but not expulsive manoeuvres (e.g. coughing). The inability to perform expulsive behaviours might underlie the increased susceptibility of older individuals to respiratory tract infections.
Abstract:
Type IIx and/or IIb diaphragm muscle (DIAm) fibres make up more fatigable motor units that are more vulnerable to sarcopenia, i.e. age-associated reductions of specific force and cross-sectional area. In contrast, type I and IIa DIAm fibres form fatigue-resistant motor units that are relatively unchanged with age. The fatigue resistance of the DIAm is assessed by normalizing the residual force generated after a period of repeated supramaximal stimulation (e.g. 120 s) to the initial maximal force. Given that sarcopenia primarily affects more fatigable DIAm motor units, apparent fatigue resistance improves with ageing. However, the central question is whether there is an ageing-related difference in the residual force generated by the DIAm after repeated stimulation and whether this force is sufficient to sustain ventilatory behaviours of DIAm. In 6- and 24-month-old Fischer 344 rats, we assessed the loss of ex vivo DIAm force throughout 120 s of repeated supramaximal stimulation at 10, 40 and 75 Hz. We found that relative fatigue resistance improved in older rats at 40 and 75 Hz stimulation. Across all stimulation frequencies, DIAm residual force was unchanged with age (∼5 N cm-2 ). We conclude that ageing increases the relative contribution of type I and IIa fibres to DIAm force, with decreased contributions of type IIx and/or IIb fibres. The residual force generated by the DIAm after repeated stimulation is sufficient to accomplish ventilatory behaviours, regardless of age.
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