Longevity & AgingPeroxisome Decline in Muscle Drives Accelerated Aging and Weakness
Researchers generated a muscle-specific mouse model lacking Pex5, a key peroxisomal import receptor, to investigate peroxisome function in skeletal muscle. Loss of Pex5 caused impaired lipid metabolism, reduced muscle force, and poor exercise performance. Mitochondrial structure, content, and function deteriorated progressively, accompanied by sarcomere disorganization, neuromuscular junction degeneration, protein aggregate accumulation, and muscle atrophy. These changes mirrored accelerated aging phenotypes. Critically, natural aging in control mice also showed declining peroxisomal content in muscle, suggesting peroxisomal decline is a genuine feature of normal aging. The findings establish a previously underappreciated role for peroxisomes and their crosstalk with mitochondria in maintaining skeletal muscle health.
