Short-term treatment of Tat-Beclin1 and endurance exercise enhances autophagy and increases grip strength in old male mice but not in female

Abstract

Sarcopenia is a geriatric disease causing loss of muscle mass and function, ultimately declining quality of life and causing death. Despite substantial efforts to prevent sarcopenia, there are no approved drugs for treating this muscle disease. Autophagy, a critical process for maintaining muscle health, offers potential avenues for intervention. However, an integrative therapy comprised of an autophagic-specific compound and endurance exercise in old animals has yet to be tested. We hypothesize that combining Tat-Beclin1 (a potent autophagy-specific inducer) and endurance exercise improves muscle force and autophagy in both male and female old mice. Female and male mice at 23 months of age were divided into four groups: Control, Tat-Beclin1 (TB), endurance exercise (Exe), and TB+Exe. Short-term combined treatment underwent for one month. Exercise training at moderate intensity (70% of running peak test) was performed on Mondays, Wednesdays, and Fridays. Tat-Beclin1 administration (15 mg/kg/day) was conducted on Tuesdays and Thursdays. We assessed muscle function through forelimb grip strength and muscle autophagic markers by western blotting. There was no difference in grip strength in female groups. In contrast, there was an increase in grip strength in treated male mice (p<0.05; TB, Exe, and TB+Exe vs. Control group). Notably, the combination treatment in the TB+Exe group outperformed the individual treatments (TB and Exe groups) in enhancing grip strength (p=0.05). Beclin1 and GLIPR2 (a novel autophagic suppressor) were unchanged in both male and female mice. Sequestosome/p62 was decreased in males only, indicating autophagy cargo degradation. Our findings demonstrate that a short-term treatment of Tat-Beclin1 combined with endurance exercise improves grip strength (muscle force) and autophagy in old male mice. Notably, female mice did not exhibit a similar response to the short-term treatment, suggesting that a more extended therapy duration may be necessary to explore potential benefits for female mice. This synergy of an autophagic-specific agonist with endurance exercise may represent a novel strategy to tackle sarcopenia. Camden Health Research Initiative - Startup fundings. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.