mTOR inhibition improves immune function in the elderly
mTOR inhibition improves immune function in the elderly
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DOI：
10.1126/scitranslmed.3009892
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发表时间：
2014-12-24
影响因子：
17.1
通讯作者：
Klickstein, Lloyd B.
中科院分区：
文献类型：
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作者：
Mannick, Joan B.;Del Giudice, Giuseppe;Klickstein, Lloyd B.
抑制哺乳动物雷帕霉素靶蛋白（mTOR）通路延长了迄今为止研究的所有物种的寿命，并在小鼠中延迟了年龄相关疾病和合并症的发作。然而，目前尚不清楚mTOR抑制是否会影响人类的衰老或其后果。为了开始评估mTOR抑制对人类衰老相关疾病的影响，我们评估了mTOR抑制剂RAD 001是否改善了老年志愿者的免疫衰老（衰老期间免疫功能的下降），通过他们对流感疫苗接种的反应进行评估。在耐受性相对较好的剂量下，RAD 001将对流感疫苗的反应增强了约20%。RAD 001还降低了表达程序性死亡-1（PD-1）受体的CD 4和CD 8 T淋巴细胞的百分比，该受体抑制T细胞信号传导，并且随着年龄的增长而更高地表达。这些结果提高了mTOR抑制可能对老年人的免疫衰老具有有益影响的可能性。
Inhibition of the mammalian target of rapamycin (mTOR) pathway extends life span in all species studied to date, and in mice delays the onset of age-related diseases and comorbidities. However, it is unknown if mTOR inhibition affects aging or its consequences in humans. To begin to assess the effects of mTOR inhibition on human aging-related conditions, we evaluated whether the mTOR inhibitor RAD001 ameliorated immunosenescence (the decline in immune function during aging) in elderly volunteers, as assessed by their response to influenza vaccination. RAD001 enhanced the response to the influenza vaccine by about 20% at doses that were relatively well tolerated. RAD001 also reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. These results raise the possibility that mTOR inhibition may have beneficial effects on immunosenescence in the elderly.