Aging skeletal muscle shows impaired mitochondrial function, altered redox regulation, disrupted fusion-fission balance, and reduced mitochondrial turnover. This translational systematic synthesis and meta-analysis evaluated whether exercise training remodels mitochondrial and functional outcomes in aging muscle. PubMed, EMBASE, and Web of Science were searched to June 26, 2026 following PRISMA 2020. Twenty-eight studies involving aged exercise groups compared to sedentary groups were included. Outcomes covered oxidative stress, mitochondrial dynamics, mitophagy, mitochondrial biogenesis/function, skeletal muscle morphology, and physiological performance. Random-effects meta-analysis showed a significant improvement in VO₂max/VO₂peak after exercise training (SMD = 0.46, p < 0.001; I² = 0%), whereas pooled changes in citrate synthase (SMD = 0.18, p = 0.450) and BMI (SMD = -0.09, p = 0.557) were not significant. The directional synthesis showed that mitochondrial biogenesis and function were consistently responsive across species, particularly for OXPHOS proteins, mitochondrial volume density, ATPmax, and SIRT1/SIRT3 signaling. Human and rodent studies assessed different, only partly overlapping mitophagy and mitochondrial dynamics markers. Therefore, differences in pathway responsiveness across species cannot be separated from differences in which markers were measured. Exercise training and lifelong physical activity were associated with changes in mitochondrial biogenesis, dynamics, mitophagy-related signaling, and muscle function in aging skeletal muscle. The observed patterns varied by training protocol and study design, but indirect comparisons and heterogeneous outcome measures preclude conclusions about the superiority of any modality. Human and rodent findings should therefore be interpreted as complementary evidence rather than equivalent estimates of biological response.
