Impaired age-associated mitochondrial translation is mitigated by exercise and PGC-1α

Area of Science:

• Muscle physiology
• Mitochondrial biology
• Aging research

Background:

• Sarcopenia, characterized by age-related skeletal muscle mass and function decline, is linked to mitochondrial dysfunction and proteostasis imbalance.
• The precise regulatory link between these mitochondrial processes in muscle aging remains unclear.

Purpose of the Study:

• To investigate the impact of aging on mitochondrial proteostasis in skeletal muscle.
• To elucidate the regulatory mechanisms governing mitochondrial translation during muscle aging.
• To determine the effect of exercise on mitochondrial proteostasis in the context of sarcopenia.

Main Methods:

• Analysis of mitochondrial proteostasis in sarcopenic skeletal muscle models.
• Investigation of regulatory roles for peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) and estrogen-related receptor α (ERRα).
• Assessment of exercise interventions on mitochondrial translation and quality control pathways.

Main Results:

• Sarcopenic muscle exhibits significant impairment in mitochondrial translation.
• PGC-1α and ERRα were identified as key regulators of this mitochondrial translation impairment.
• Exercise training reversed age-related mitochondrial translation deficits and enhanced quality control mechanisms.

Conclusions:

• Mitochondrial proteostasis is critical in skeletal muscle aging and sarcopenia development.
• Dysregulation of PGC-1α and ERRα contributes to impaired mitochondrial function in aging muscle.
• Physical activity effectively restores mitochondrial translation and quality control, underscoring its therapeutic potential against sarcopenia.