Exercise prevents the negative impact of prolonged inactivity in Drosophila

Prolonged inactivity due to medical conditions can cause chronic muscle disuse and lead to physical incapacity and poor quality of life. Here, we developed a Drosophila model of confinement inactivity (CI) to observe its effects on lifespan and muscle function. We found that CI substantially impacted longevity and function; confined flies had impaired mobility, shorter lifespan, and reduced muscle integrity compared to their freely mobile siblings. Furthermore, we found that temporarily alleviating CI with physical exercise ameliorated negative effects, in part by improving muscle homeostasis. Finally, we tested whether muscle overexpression of 3 exercise-responsive genes, dPGC-1⍺, dFNDC5, or dSesn, could prevent the negative impact of CI on fly aging, even without physical exercise. We found that when overexpressed in muscle, dSesn prevented premature declines in endurance, and dFNDC5 protected speed and endurance.