Aerobic Exercise Improves Mitochondrial Function in Sarcopenia Mice Through Sestrin2 in an AMPKα2-Dependent Manner

Area of Science:

• Gerontology and Exercise Physiology
• Molecular Biology and Cellular Metabolism

Background:

• Sarcopenia, an age-related decline in muscle, increases health risks in older adults.
• The molecular mechanisms underlying sarcopenia and exercise's benefits remain incompletely understood.

Purpose of the Study:

• To investigate the molecular pathways through which exercise mitigates sarcopenia.
• To elucidate the role of Sestrin2 (Sesn2) and AMP-activated protein kinase α2 (AMPKα2) in exercise-induced muscle adaptation.

Main Methods:

• Utilized knockout/silencing models of Sesn2 in vitro and in vivo.
• Assessed mitochondrial dynamics, biogenesis, and mitophagy.
• Examined the effects of aerobic exercise and Sesn2 overexpression.
• Investigated the dependency of Sesn2's effects on AMPKα2.

Main Results:

• Sarcopenia-induced muscle deficits were reversed by exercise.
• Sesn2 deficiency disrupted mitochondrial homeostasis, which was rescued by exercise or Sesn2 re-expression.
• Sesn2's impact on mitochondrial function was mediated by AMPKα2.

Conclusions:

• Aerobic exercise ameliorates sarcopenia by activating the Sesn2/AMPKα2 signaling pathway.
• This pathway is crucial for maintaining mitochondrial quality control and function during aging.
• The Sesn2/AMPKα2 axis offers a novel molecular target for sarcopenia interventions.