MUSCULAR AND METABOLIC CONSEQUENCES OF PROLONGED PHYSICAL INACTIVITY AND SUBSEQUENT RETRAINING

Physical inactivity, ranging from modest reductions in daily activity to severe disuse models such as bed rest, induces rapid and profound impairments in cardiovascular, muscular, and metabolic function. This thesis investigated the integrative effects of inactivity on skeletal muscle oxidative capacity, oxygen transport, and metabolic regulation, further exploring the potential of exercise training to restore these functions. Using horizontal bed rest study design, we assessed the effect of 21 days (BR21) and 10 days (BR10) of severe disuse in young (n=9; 23±4 yrs) and elderly (n=10; 69±3 yrs) participants respectively, followed by 3 weeks of endurance re-training period (rTR). We assessed non-invasively the vastus lateralis oxidative capacity and sensitivity to oxygen diffusion during experimental sessions trough Near Infrared Spectroscopy (NIRS). Young participants demonstrated a significant reduction in oxidative capacity (k; p = 0.006), while elderly participants showed a non-significant trend toward decline (p = 0.186) . Interestingly, both groups recovered baseline levels of oxidative capacity after endurance re-training (both p > 0.05 when compared to baseline), with elderly participants exhibiting greater relative improvements, possibly reflecting a higher proportion of oxidative fibers and lower baseline mitochondrial capacity. In parallel, quadriceps cross-sectional area decreased markedly in both groups, indicating structural atrophy. Sensitivity to oxygen diffusion was significantly above zero at baseline in young participants and decreased to zero following bed rest in both groups, suggesting a shift in limitation from diffusive transport toward intracellular oxidative metabolism. These findings highlight that muscle mass and oxidative function are differentially affected during disuse and that recovery potential may vary with age. Then, using a step-reduction study, we investigated mild disuse, reproducing real-world scenario of sedentary lifestyle. Young adults (n= 32; 15 M; 23 ± 3 yrs) reduced daily steps (SR) from ~8,000 to ~1,500 for 14 days and then were randomly assigned to endurance, strength or return to habitual life re-training period, for the duration of 3 weeks. Mild inactivity impaired peak oxygen uptake, cardiac output, and muscle oxidative function (all p < 0.05), while promoting insulin resistance despite stable diet and body weight. During recovery, endurance training fully restored aerobic capacity and oxidative function (both p < 0.05), whereas strength training and resumption of habitual activity provided only partial benefits. However, insulin resistance persisted after retraining (p < 0.05 compared to baseline), suggesting longer or more targeted interventions are required to restore metabolic health. These results confirm that even short-term reductions in activity compromise both central and peripheral determinants of oxygen transport and disrupt glucose homeostasis. During the recovery phase, endurance training effectively restored several of these impairments, whereas strength training or return to habitual life provided only limited benefits. Together, these studies demonstrate that physical inactivity rapidly impairs central and peripheral component of oxygen cascade, and metabolic regulation, with endurance training showing the greatest benefits. The findings emphasize the central role of skeletal muscle plasticity during muscle disuse highlighting the importance of continuous physical activity in mitigating the health risks associated with sedentary behaviour.