Endurance Training Restores Ageing-Impaired Lysosomal Biogenesis Factors in Rest and Response to Acute Exercise in Rat Skeletal Muscle

PURPOSE: Lysosomes, crucial for autophagy, play a pivotal role in cellular processes influenced by exercise. This study investigates the impact of ageing on lysosomal function, focusing on Transcription Factor E3 and its regulators, mTORC1 and Calcineurin, emphasizing their response and adaptation to endurance training METHODS: Twenty-five male Sprague-Dawley rats were categorised into Young (2 months), Aged sedentary and Aged sedentary single session (18 months), Aged long-term trained, and Aged trained-single session (17 months). Changes in variables were explored concerning sarcopenia by Soleus muscle fibre diameter and number measured via Eosin & Hematoxylin, phosphorylated and total TFE3 protein levels via western blot, mTORC1 and Calcineurin mRNA levels via real-time PCR. RESULTS: Ageing occurred with increased pTFE3/TFE3total protein (BF=579), declined mTORC1 mRNA (BF=3.99), and muscle diameter (BF=87), signifying sarcopenia and potential contributors. Conversely, Calcineurin mRNA (BF=0.67) and muscle fibre number (BF=0.31) remained unaltered during ageing. Exercise elicited acute responses, reducing pTFE3/TFE3total protein (BF=306), elevating mTORC1 (BF=1.57) and Calcineurin mRNA levels (BF=3.19). Three weeks of endurance training further decreased resting pTFE3/TFE3total protein (BF=174) while increasing Calcineurin mRNA (BF=12) and muscle fibre diameter (BF=126), with no changes in mTORC1 mRNA levels (BF=0.46) and muscle fibre number. Post-exercise, trained rats sustained decreased pTFE3/TFE3total protein (BF=56) and elevated mTORC1 mRNA (BF=1.16). CONCLUSION: This study underscores the involvement of TFE3, MTORC1, and Calcineurin in sarcopenia, proposing endurance training as an effective strategy to mitigate age-related changes and enhance muscle function in aged rats. Additionally, it suggests impairments in TFE3 possibly contribute to sarcopenia.