Effects of Statin Treatment on Muscular and Cardiorespiratory Adaptations to High Intensity Interval Training in Aged Mice

Our lab has previously shown that High-Intensity Interval training (HIIT) positively benefits muscle strength and cardiorespiratory fitness in aged mice. However, it is unknown if statin treatment negatively impacts adaptations to HIIT as we have previously shown in young mice following running wheel or treadmill training. To date, no studies have investigated the impact of statin treatment on muscle function and fitness in aged mice performing HIIT. PURPOSE: These experiments tested the hypothesis that statin treatment will negatively impact skeletal muscle and cardiorespiratory adaptations to HIIT in aged mice. METHODS: Aged C57 mice (22-26 months) were divided into 4 groups (n= 6/group) and completed 4 weeks of HIIT or normal cage activity (CON) while receiving daily placebo or atorvastatin (30 mg/kg). Cardiorespiratory adaptations and sprinting capacity were assessed with maximal treadmill and sprint speed tests before and after 4 weeks of HIIT or CON. HIIT was performed 3 times/week on an incline treadmill with increasing intensity over 4 weeks. In-vivo plantarflexor force and fatigue resistance (% of maximal force after 10 contractions) assessed muscle force and fatigability after 4 weeks of HIIT or CON. Two-way ANOVAs compared main effects of statins and training and their interaction. RESULTS: HIIT significantly increased maximal treadmill time and sprint speed in both trained groups (p< 0.05). HIIT increased treadmill time 541±148 s and 475±187 s for placebo and statin mice, respectively, compared to 1.5±63 s and 18±28 s increases, respectively for placebo and statin CON. HIIT increased sprint speed 3.3±1.9 m/s and 6.8±2.3 m/s for placebo and statin mice, respectively, compared to 2.2±5.6 m/s and -4.5±2.0 m/s increases, respectively, in placebo and statin CON. Statin treatment improved muscle fatigue resistance compared to placebo in HIIT group only (CON: 37±2 and 40±4; HITT: 33±2 and 49±3% of max for placebo and statin, respectively, p< 0.05). Statin treatment significantly decreased force in both control and HIIT (CON: 1.4±0.04 and 1.2±0.9; HITT: 1.4±0.1 and 1.0±0.2 g/g body mass for placebo and statin, respectively, p< 0.05). CONCLUSIONS: These findings demonstrate HIIT significantly increases cardiorespiratory endurance and sprint speed in both placebo and statin groups. However, statin treatment was associated with reductions in muscle strength in both CON and HIIT groups. Statin treatment alone negatively impacted sprint speed in CON mice as evidenced by reductions in speed after 4 weeks of statins. Taken together these results suggest statins negatively impact muscle strength and power but the effects were not exacerbated with exercise. Surprisingly, statin treatment was associated with improved muscle fatigue resistance in HIIT mice. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.