P. Schematic model of the mechanism. In young flies highly expressed LAS synthesizes sufficient ALA in ISCs. ALA promotes endosome formation and maturation in ISCs, which in turn maintains the proper activation of autophagy and prevents the over activation of EGFR signaling in ISCs. As a secondary effect, ALA also prevents ISC overproliferation by scavenging excessive ROS. When flies get old, the expression of LAS dramatically reduces, which causes ALA deficiency and endosome reduction in ISCs. Ultimately, this leads to the hyperproliferation of ISCs with age. 