The underlying cause for overactivation of mTOR in the HSCs from the aging mice remains to be resolved. PTEN (phosphatase and tensin homolog deleted from chromosome 10) dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate (25), indirectly repressing AKT phosphorylation and thereby decreasing mTOR activity(26), and previous studies have shown that HSCs lacking PTEN show mTOR-dependent functional defects (27, 28). However, our data show that the amount of phosphorylated AKT in HSCs from young mice and that from old mice are substantially the same. Therefore, it is unlikely that overactivation of AKT is responsible for mTOR-dependent HSC aging.