Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
Sci Transl Med. 2014 Dec 24;6(268):268ra179. doi: 10.1126/scitranslmed.3009892.
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.
哺乳动物雷帕霉素靶蛋白（mTOR）通路的抑制作用延长了迄今为止所有研究物种的寿命，并可延缓与年龄相关的疾病和合并症的发生。然而，尚不清楚 mTOR 抑制是否会影响人类的衰老或衰老的后果。为了开始评估 mTOR 抑制对人类与衰老相关条件的影响，我们评估了 mTOR 抑制剂 RAD001 是否可以改善老年志愿者的免疫衰老（即衰老过程中免疫功能的下降），方法是评估他们对流感疫苗的反应。RAD001 在相对耐受的剂量下使流感疫苗的反应增强了约 20%。RAD001 还降低了表达程序性死亡-1（PD-1）受体的 CD4 和 CD8 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表达更高。这些结果提出了这样一种可能性，即 mTOR 抑制可能对老年人的免疫衰老具有有益的影响。
