Qi Haiyan, Su Feng-Yun, Wan Shan, Chen Yongjie, Cheng Yan-Qiong, Liu Ai-Jun
Springcell Corporation, Dayton, NJ, USA.
CNS Neurosci Ther. 2014 Nov;20(11):991-8. doi: 10.1111/cns.12338.
The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC1 inhibition that inhibits cell proliferation and increases autophagy. However, rapamycin also exhibits a number of harmful adverse effects. Whether rapamycin can be developed into an antiaging agent remains unclear.
We demonstrated that rapamycin at micro-doses (below the TORC1 inhibiting concentration) exhibits a cell-protective activity: (1) It protects cultured neurons against neurotoxin MPP(+) and H2O2. (2) It increases survival time of neuron in culture. (3) It maintains the nonproliferative state of cultured senescent human fibroblasts and prevents cell death induced by telomere dysfunction. (4) In animal models, it decreased the cerebral infarct sizes induced by acute ischemia and dramatically extended the life span of stroke prone spontaneously hypertensive rats (SHR-SPs).
We propose that rapamycin at micro-dose can be developed into an antiaging agent with a novel mechanism.
免疫抑制剂雷帕霉素据报道具有抗衰老活性，这归因于其对TORC1的抑制作用，该抑制作用可抑制细胞增殖并增强自噬。然而，雷帕霉素也表现出许多有害的副作用。雷帕霉素是否能够被开发成为一种抗衰老药物仍不明确。
我们证明，微剂量的雷帕霉素（低于TORC1抑制浓度）具有细胞保护活性：（1）它保护培养的神经元免受神经毒素MPP(+)和H2O2的损伤。（2）它延长了培养神经元的存活时间。（3）它维持培养的衰老人类成纤维细胞的非增殖状态，并防止端粒功能障碍诱导的细胞死亡。（4）在动物模型中，它减小了急性缺血诱导的脑梗死面积，并显著延长了易中风自发性高血压大鼠（SHR-SPs）的寿命。
我们提出，微剂量的雷帕霉素可以被开发成为一种具有新机制的抗衰老药物。
