Targeting mitochondrial quality control for treating sarcopenia: lessons from physical exercise

ABSTRACT

Introduction: Mitochondrial dysfunction is a hallmark of aging and hence is a candidate target for intervention. Sarcopenia of aging is a prevalent condition and is associated with numerous negative health outcomes. Alterations in mitochondrial homeostasis have been reported in sarcopenic muscle.

Area covered: We discuss the evidence that points to mitochondrial dysfunction having a causative role in sarcopenia and the mechanisms involved in the accumulation of damaged mitochondria in the aged muscle. We also discuss the effects of physical exercise on mitochondrial quality control and muscle health in advanced age.

Expert opinion: In the aged muscle, the mitochondrial quality control axis is altered at several levels, including proteostasis, biogenesis, dynamics, and autophagy. Mitochondrial dysfunction arising from impaired quality control is thought to play a major role in the pathogenesis of sarcopenia. Physical exercise is the most effective strategy for the management of sarcopenia. Improvements in mitochondrial health and plasticity may mediate several beneficial effects of exercise in muscle. A greater understanding of the molecular changes that occur in the aged muscle following exercise and how they impact mitochondrial homeostasis is necessary for the exploration of potential targets that are amenable for interventions.

KEYWORDS:

• autophagy
• mitochondrial dynamics
• mitochondrial biogenesis
• mitochondrial proteostasis
• mitophagy
• physical activity
• physical exercise
• resistance training

Article Highlights

• Sarcopenia is the age-related loss of muscle mass and strength/function and is associated with several negative health-related events.

• A set of interrelated processes referred to as mitochondrial quality control (MQC) (proteostasis, biogenesis, dynamics, and mitophagy) is in place to ensure muscle cell homeostasis.

• Mitochondrial dysfunction amplified by failing quality control mechanisms, is considered to be a relevant player in the pathophysiology of sarcopenia.

• Preclinical and clinical evidence suggests that physical exercise modulates MQC in muscle.

• Current unknowns include the optimal window of exercise training interventions (timing and intensity) able to improve MQC function to prevent/combat sarcopenia.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Fondazione Roma [Non-Communicable Diseases call for proposals 2013], Innovative Medicine Initiative-Joint Undertaking [IMI-JU #115621], Intramural Research Grants from the Università Cattolica del Sacro Cuore [D3.2 2013 and D3.2 2015], the nonprofit research foundation ‘Centro Studi Achille e Linda Lorenzon’, and the National Institute on Aging [R01AG17994].