Impacts of Combining Tat-Beclin1 and Endurance Exercise on Myofiber Characteristics in Aged Mice

Sarcopenia is an aging-associated muscle deterioration characterized by myofiber atrophy and dysfunction that preferentially affects type II fibers, resulting in the fast-to-slow fiber-type shifting that ultimately reduce muscle strength. There is no effective drugs that, when combined with exercise prevent sarcopenia maladaptation in myofibers. The goal of this study is to determine whether combining Tat-Beclin1 (TB), a small peptide compound that induces autophagy, and endurance exercise (Exe) increases type II myofibers in aged male and females. We hypothesized that combining TB with Exe would increase type II myofibers size and proportion. For one month, 22-23-month-old male and female mice were treated with TB (15 mg/kg/day) every Tuesday and Thursday, and performed Exe every Monday, Wednesday, and Friday. We stained the tibialis anterior muscle for laminin, type IIA and type IIB myofibers, and quantified the cross-sectional area (CSA), the indicator of myofiber size, and analyzed the distribution pattern of myofibers. Our results revealed that there was no significant change in the CSA of myofiber in male and female animals in response to the treatment. Notably, analysis of myofiber distribution pattern showed that only female animals subjected to the integrative treatment exhibited a significant increase in the percentage of the fastest and most glycolytic type IIB myofibers, which ranged from 1500 square micrometers (μm2) to 2000 μm2, and a corresponding decrease in the more oxidative and less glycolytic type IIA myofibers ranged from 1000 μm2 to 1500 μm2, indicating a shift towards power. Given that the fast-to-slow fiber-type transition is a critical sarcopenic phenotype, our findings suggest the potential therapeutic effect of integrating exercise training and Tat-Beclin1 treatment on attenuating sarcopenia via preserving, or increasing the type IIB myofibers in females, but not males. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.