Introduction Prolonged muscle disuse, as is often observed in long-term hospitalization, can have deleterious effects on muscle health. The aging population, which is more prone to lengthy hospital stays, has shown an increased risk of suffering from the impact of bedrest and presents greater rate of muscle atrophy and muscle weakness. An exercise countermeasure therefore presents itself as a prime solution to mitigate the effect of bedrest. Yet, little to no studies have investigated the impact of an exercise countermeasure on muscle atrophy, strength loss and muscle proteome dynamics in an aging population subjected to prolonged muscle disuse.

Methods We therefore sought to verify how a mixed exercise program affects muscle health and performances in active older adults aged 55 to 65 (n=20, 9 men and 11 women) subjected to 14 days of continuous head-down tilt bedrest. Half of the participants engaged in a daily mixed exercise program for an hour in addition to receiving passive mobilizations, while the other half received only passive mobilizations. Total muscle mass was estimated with DXA, and muscle volume and fat infiltration were measured with MRI. Knee extensor strength was measured isometrically with Biodex system at a 90° angle. To better understand the mechanisms at play, muscle biopsies were taken on the outer part of the quadriceps muscle on day 1, 3, 8 and 14 of bedrest and muscle proteomics analyses were done by tandem mass spectrometry. Finally, inflammatory markers (TNF-α, IL-6, IL-8), myostatin, and heat-shock protein 27 and 72 were measured in plasma before and after bedrest. Follow-up measurements were repeated after 4 weeks and 4 months. The effect of time and group, and their interaction was verified with mixed-effect models.

Preliminary results 14 days of continuous head-down bedrest induced changes in knee extensor strength in both group (p<0.001) without a group-by-time interaction (p=0.37). Total lean mass estimated with DXA decreased after bedrest (p=0.004) and returned to normal after 4 weeks without a group effect (p=0.93). MRI however showed a group-by-time interaction for changes in quadriceps muscle volume (Change from baseline to end of bedrest: Control: -6.2% CI [-8.3, -4.0%]; Exercise: -0.8% CI [-2.5, 0.9%],  p<0.01), with exercise mitigating the impact of bedrest. So far, the changes in protein abundance between day 1 and 14 of bedrest are related to biological processes of innate immunity and inflammation. These changes in protein abundance were however not reflected in systemic inflammation as there was no change from baseline in IL-6, IL-8 or TNF-α throughout the duration of the study (p≥0.2 for all).

Conclusion Altogether, our preliminary analyses show that engaging in an hour of mixed exercise everyday mitigated the effect of 14 days of head-down bedrest on quadriceps muscle volume. It did not, however, counter the loss of strength. Additional analyses will be done in muscle biopsies and in plasma to better understand the mechanisms at play and full data will be presented at the Physiological Society Conference.

Ethical statement Participants gave their informed and written consent before participating in this study.