Inorganic phosphate (Pi) has been implicated in the pathogenesis of accelerated aging; however, the underlying mechanisms remain elusive. Herein, we demonstrated in cultured cells and in vivo that increased levels of extracellular Pi activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway by suppressing membrane-bound phosphatase and tensin homolog (PTEN) levels in a manner requiring the sodium-dependent Pi transporter PiT-1. High levels of extracellular Pi also led to phosphorylation of Ser/Thr clusters in the C-terminal tail of PTEN, which has been shown to dissociate PTEN from the membrane. Notably, blockade of mTORC1 activity by rapamycin treatment prolonged the life span of hyperphosphatemic α-Klotho–deficient (Kl^–/–) mice. Dietary correction of hyperphosphatemia or treatment with rapamycin also rescued the brown adipose tissue dysfunction and oxidative damage observed in Kl^–/– mice. Furthermore, rapamycin treatment partially rescued these effects and extended the life span when Kl^–/– mice were maintained on a high-phosphate diet. Finally, rapamycin reduced circulating Pi levels in Kl^–/– mice, apparently by decreasing the localization of sodium-dependent Pi transport protein 2a at the renal brush border membrane. Therefore, the activation of mTORC1 may create a vicious loop that exacerbates the retention of Pi, which in turn may enhance oxidative damage and ultimately shorten the life span of Kl^–/– mice. These results demonstrate that Pi has important roles in the aging process, and the blockade of mTORC1 may have therapeutic potential for premature aging-like symptoms associated with hyperphosphatemia.