Combined Effects of 8 Weeks of Endurance Training and MitoQ Antioxidant Supplementation on PGC-1α and PDK4 Gene Expression in Skeletal Muscle of Young and Aged Male Wistar Rats

Aging-associated mitochondrial dysfunction has been linked to suppressed expression of PGC-1α and PDK4 in skeletal muscle. This study examined the effects of 8 weeks of endurance training and MitoQ supplementation, alone and combined, on PGC-1α and PDK4 mRNA expression and systemic oxidative stress markers in aged (20–24 months) and young (8-week-old) male Wistar rats. Sixty-four animals were initially enrolled (n = 8/group per age cohort: Control [CON], Training [TR], Supplement [SUP], Training+Supplement [TR + SUP]); final analyzed sample sizes were n = 8 for all young groups and the aged TR group, and n = 7 for the aged CON, SUP, and TR + SUP groups. Training was performed five days per week at progressively increasing intensity (50–70% of estimated VO₂max); MitoQ was administered at 250 µM in drinking water. Gene expression was quantified by RT-qPCR using 18S rRNA as the reference gene. Both genes showed significant age × intervention interactions (PGC-1α, P < 0.001; PDK4, P = 0.006). In young rats, TR + SUP produced the largest response for both genes (PGC-1α, 4.25-fold; PDK4, 2.23-fold, vs CON); a training × supplement interaction test confirmed true synergy for PGC-1α (P = 0.003) but not for PDK4 (P = 0.14) in young muscle. Aged muscle retained a partial, MitoQ-associated PGC-1α response — SUP and TR + SUP were significantly elevated versus aged CON (both P < 0.05) — although absolute expression remained far below young muscle at every intervention level. For PDK4, neither training nor MitoQ alone significantly altered expression in aged muscle, but their combination did, exceeding both single interventions (TR + SUP vs TR, P = 0.001; vs SUP, P = 0.015) and reflecting a training × supplement interaction specific to aged muscle (P = 0.002). Serum MDA was higher in aged than young rats (P < 0.001), and SOD activity was modestly elevated in aged trained/supplemented groups (P = 0.015); GPX did not differ across groups. These findings indicate that the combination of endurance training and MitoQ can produce genuine synergistic transcriptional effects, but that the specific gene and age context determines whether synergy, additivity, or blunted responsiveness predominates.