Bed rest and endurance retraining alter persistent inward current estimates in young and older males.

Introduction: Prolonged physical inactivity induces rapid neuromuscular deconditioning, with aging influencing both the rate, recovery and nature of these changes. However, its effects on the modulation of motoneuron excitability across age groups remain unclear. This study examined how bed rest and subsequent endurance retraining influence persistent inward current (PIC)-related estimates, motor-unit (MU) discharge behavior, and circulating tryptophan (TRP) and kynurenine (KYN) biomarkers in healthy young and older males. Methods: Nine young (22 ± 4 yr) and ten older (69 ± 3 yr) males completed 21 and 10 days of horizontal bed rest, respectively, followed by 21-day endurance retraining. High-density surface EMG decomposition of vastus lateralis was used to estimate PIC-related indices derived from paired MU analysis (ΔF) and geometric discharge metrics, namely brace height (BH), acceleration (ACC), and attenuation (ATT), as well as MU discharge properties, including peak discharge rate and discharge-rate ranges. Plasma TRP, KYN, and their concentration ratio were also quantified. Results: Bed rest reduced ΔF in YA after 21 days (-26.1%, p<0.001) and in OA after 10 days (-15.3%, p=0.029). After retraining, ΔF was no longer different from baseline in YA, whereas in OA values at RT did not differ from either baseline or bed rest. In YA, ACC (-25.1%, p=0.002) and ATT (-27.7%, p=0.023), but not BH, decreased after bed rest and were no longer different from baseline after retraining; in OA, BH, ACC, and ATT were unchanged. Peak discharge rate and discharge-rate range decreased after bed rest in both groups and showed partial recovery after retraining. Plasma tryptophan, kynurenine, and their ratio did not change. Discussion: These findings indicate that motoneuron-related indices are sensitive to prolonged physical inactivity and remain modifiable during post-disuse retraining. Although older adults were exposed to a shorter bed rest duration, ΔF adaptations to disuse and retraining were also present in an older population. The non-uniform behavior of ΔF and geometric discharge metrics suggests that different aspects of motoneuron output may adapt through partly distinct mechanisms, potentially with age-dependent features.