Adding Tat-Beclin1 to an endurance training program promotes additive improvements in physical function in aged male mice.

Autophagy is a hallmark of aging, but it has not been exclusively targeted to attenuate aging-related physical dysfunction. Here, we combined Tat-Beclin1 and endurance training to determine its effect on physical function domains in aged male mice. Mice were randomly divided into Control (N = 5), Tat-Beclin1 (TB, 15 mg/kg, 2×/week, N = 9), Exercise (Exe, 70%-maximal-running-speed, 3×/week, N = 9), and TB+Exe (N = 8) for 1 month in 23-month-old male C57BL/6J mice. Animals were assessed for grip strength (GS), endurance capacity (EC) on a treadmill, and balance and coordination on a rotarod. Gastrocnemius/plantaris (G/P) and tibialis anterior muscles were harvested for western blotting, myofiber typing, and proteomic profiling (G/P only). Although no significant interaction was observed, the TB+Exe group showed improvements in GS, EC, and balance and coordination performance, an outcome comparable with additive effects of both therapies. Limited changes were observed in myofiber typing and autophagy markers among groups. A proteomic analysis revealed that TB upregulated biological processes involved in muscle contraction, whereas TB+Exe surprisingly upregulated acute inflammatory responses, including proteins such as haptoglobin and orosomucoid-1. Altogether, combining TB and endurance training elicits additive effects on physical functions of aged male mice and may represent a new approach to attenuate aging-related physical dysfunction.