BACKGROUND: mitophagy, a process that is responsible for eliminating damaged mitochondria, gradually declines during aging. This decline, particularly prominent in aging skeletal muscle, correlates with compromised mitochondrial function, impacting mobility and muscle strength in older individuals. Previous research demonstrates that after 6 hours of acute exercise, young mice exhibit heightened mitophagy compared to their sedentary counterparts. However, many studies revealed that the accumulation of damaged mitochondria due to oxidative stress, DNA mutations and dysfunctional lysosome can overwhelm the mitophagy process, reducing its efficiency in removing dysfunctional mitochondria in aged skeletal muscle. Therefore, our hypothesis is exercise-induced mitophagy in skeletal muscle is impaired with aging. METHODS: We transfected pMito-timer into Flexor digitorum brevis (FDB) muscle of 3 (young) and 25 (old) month old mice. After 10 days recovery, mice were familiarized to treadmill running for three days (10 min at 10m/min). On the fourth day, mice performed 90 minutes treadmill running exercise. Young mice ran 10 min at 13m/min, 10 minutes at speed 16m/min, 50 minutes at 19m/min, and finally 20 minutes at 21m/min. Based on the NMR data, the old mice have higher body fat mass and lower muscle mass in compare with young group. Therefore, old mice cannot have same performance as young group. In this regard, we normalized and adjusted the running protocol for workload equality. We calculated the work performance based on body weight by using the equation (Body weight (kg)*distance (m)*time (m)* 0.05 incline). Also, we monitored blood lactate before and after exercise to monitor relative exercise intensity. After 6 hours, we harvested FDB to observe mitophagy by confocal microscopy.RESULTS: Young mice had significantly higher mitophagy following exercise, as seen previously. However, mitophagy was significantly elevated in sedentary old mice compared to either young group. Furthermore, there was no effect of exercise in old mice to further elevate mitophagy above sedentary, age-matched counterparts.CONCLUSION: Our study shows age-related differences in skeletal muscle mitophagy and the mitophagy response to acute exercise. To better comprehend our findings, we need to investigate how metabolic preferences during acute exercise differ between young and old mice and how these variances impact mitophagy.

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