The ageing neuromuscular system and sarcopenia: a mitochondrial perspective.

ABSTRACT

Skeletal muscles undergo structural and functional decline with ageing, culminating in sarcopenia. The underlying neuromuscular mechanisms have been the subject of intense investigation, revealing mitochondrial abnormalities as potential culprits within both nerve and muscle cells. Implicated mechanisms involve impaired mitochondrial dynamics, reduced organelle biogenesis and quality control via mitophagy, accumulation of mitochondrial DNA (mtDNA) damage and respiratory chain defect, metabolic disturbance, pro-apoptotic signalling, and oxidative stress. This article provides an overview of the cellular mechanisms whereby mitochondria may promote maladaptive changes within motor neurons, the neuromuscular junction (NMJ) and muscle fibres. Lifelong physical activity, which promotes mitochondrial health across tissues, is emerging as an effective countermeasure for sarcopenia.