Aging Medicine (Milton (N.S.W)) · May 25, 2026

The Effect of Resistance Training and Ursolic Acid on the PI3K-AKT-mTOR Pathway in Aged Diabetic Rats: A Comparative Study

By Sadeghi A, Alizade S, Faramarzi M et al.

OBJECTIVES: Sarcopenia, characterized by age-related muscle loss, worsens in diabetes due to anabolic resistance. Ursolic acid (UA), a natural compound with anabolic and anti-catabolic effects, may mitigate sarcopenia by enhancing anabolic pathways. This study examined the effects of 8 weeks of resistance training and UA supplementation on PI3K-AKT-mTORC1 pathway proteins in muscle tissue of aged diabetic rats. METHODS: Fifty 21-month-old Wistar rats were divided into five groups: healthy control, diabetic control, diabetic + resistance training, diabetic + UA, and diabetic + resistance training + UA. Type 2 diabetes was induced using a high-fat diet and low-dose STZ. Resistance training consisted of 8 weeks of ladder climbing at 60% MVCC, 5 days per week. UA was administered daily to the UA and combination groups. Protein expression was analyzed using Western blot. RESULTS: AKT and mTORC1 or phosphorylated AKT levels did not differ significantly across groups. However, dephosphorylated PI3K (p = 0.011) and phosphorylated mTORC1 (p = 0.026) showed significant changes. PI3K expression decreased in diabetic, resistance training, and UA groups compared to controls, but not in the combination group. Phosphorylated mTORC1 was reduced in diabetic controls but maintained in the training, UA, and combination groups. CONCLUSION: Diabetes reduces PI3K and mTORC1 protein expression. Resistance training or UA alone improved mTORC1 expression, while their combination enhanced both PI3K and mTORC1, suggesting synergistic anabolic benefits. Combining UA with resistance training may counteract diabetes-induced muscle loss.

doi.org/10.1002/agm2.70071 Open access PubMed 42428682 Interventions