Exercise training and mitochondrial remodeling in aging skeletal muscle: A translational systematic review and meta-analysis.

In 30 seconds

This translational systematic review and meta-analysis examined exercise-related mitochondrial and functional changes in aging skeletal muscle, drawing on 28 studies comparing aged exercise groups with sedentary groups. Random-effects analysis found improved VO₂max/VO₂peak after training (SMD = 0.46, p < 0.001; I² = 0%), while pooled changes in citrate synthase and BMI were not significant. Across species, the directional synthesis indicated consistent responsiveness in mitochondrial biogenesis and function, including OXPHOS proteins, mitochondrial volume density, ATPmax, and SIRT1/SIRT3 signaling. Findings varied by protocol and study design.

Key findings

• Exercise training improved VO₂max/VO₂peak (SMD = 0.46, p < 0.001; I² = 0%).
• Pooled changes in citrate synthase (SMD = 0.18, p = 0.450) and BMI (SMD = -0.09, p = 0.557) were not significant.
• Mitochondrial biogenesis and function showed consistent directional responsiveness across species, including OXPHOS proteins, mitochondrial volume density, ATPmax, and SIRT1/SIRT3 signaling.
• Human and rodent studies measured partly different mitophagy and mitochondrial dynamics markers, limiting direct comparison of pathway responses.

Why it matters

The synthesis links exercise in aging muscle with both improved aerobic capacity and changes in mitochondrial biology, providing a broader view than any single biomarker or species can offer. It also highlights that measured responses depend partly on which markers and protocols studies use, so apparent differences between human and animal evidence should not be treated as direct biological contrasts.

What to keep in mind

Heterogeneous outcome measures and study designs, along with partly non-overlapping markers in human and rodent studies, limit cross-study and cross-species comparisons. Indirect comparisons do not establish superiority of any exercise modality.