Fig. 9

Proposed mechanism for how IGF-1 knockdown protects aged BM-MSCs against hypoxic injury. In young BM-MSCs, the appropriate amount of IGF-1 bound to its receptor promotes mTOR and Akt phosphorylation (activation of mTOR/Akt), thereby activating S6K and 4EBP1, which leads to the maintenance of basal autophagy. Basal autophagy maintains cell survival and thus protects the heart. In aged BM-MSCs, there is excessive IGF-1 bound to its receptor, which leads to the overactivation of mTOR/Akt, S6K, and 4EBP1; therefore, the inhibition of basal autophagy is overly promoted, which accelerates apoptosis in aged BM-MSCs. As a result, insufficient autophagy can maintain neither cell functional survival nor protect the heart