Intermittent time-restricted feeding improves physical performance and modulates mitochondrial morphology in a muscle...

Sarcopenia, defined as the age-related decline in skeletal muscle mass and function, markedly reduces physical performance, threatens functional independence, and diminishes quality of life in older adults. Although the clinical manifestations of sarcopenia typically emerge later in life, underlying molecular alterations, particularly within the mitochondrial network, occur well before symptom onset. Growing evidence indicates that dietary interventions, including caloric restriction as well as changes in meal timing, composition, and overall intake, play a critical role in attenuating age-associated pathologies. Time-restricted feeding (TRF) is a dietary regimen in which all caloric intake is confined to a defined daily time window and has emerged as a feasible and widely adopted variant of caloric restriction. This study investigates the effects of inactive phase TRF on skeletal muscle health in a middle-aged murine model, with a particular focus on its potential to delay or attenuate the decrease of physical performance only by modifying daily feeding schedules. Our findings demonstrate that inactive phase TRF allows to dissect the impact of mistimed nutrient intake and confers beneficial effects on skeletal muscle, including improved muscle strength and maintenance of basal glycemia during early aging. These effects were accompanied by a tendency to increase succinate dehydrogenase (SDH) expression and significantly reduced lipid droplet accumulation. These effects correlate with muscle type-specific adaptations of the mitochondrial network and sarcoplasmic reticulum-mitochondria interaction in response to TRF. Collectively, these findings support the potential of inactive phase TRF as an easy-to-follow therapeutic intervention during middle age to maintain physical performance in early aging.