Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Rep. 2013 Sep 12;4(5):913-20. doi: 10.1016/j.celrep.2013.07.030. Epub 2013 Aug 29.
We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR(Δ/Δ)) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While mTOR(Δ/Δ) mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTOR(Δ/Δ) mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR(Δ/Δ) mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.
我们使用雷帕霉素靶蛋白（mTOR）功能减弱的小鼠模型来分析衰老参数。具有两个功能减弱（mTOR（Δ/Δ））等位基因的小鼠是有活力的，但表达的 mTOR 约为野生型水平的 25%。这些动物表现出 mTORC1 和 mTORC2 活性降低，中位生存期延长约 20%。虽然 mTOR（Δ/Δ）小鼠比野生型小鼠小，但这些动物的标准化食物摄入量、葡萄糖稳态或代谢率没有任何改变。与它们的寿命延长一致，mTOR（Δ/Δ）小鼠表现出许多衰老组织生物标志物的减少。功能评估表明，随着 mTOR（Δ/Δ）小鼠衰老，它们在许多（但不是全部）器官系统中表现出明显的功能保存。因此，在哺乳动物模型中，尽管降低 mTOR 的表达显著增加了整体寿命，但它以节段性的方式影响组织和器官功能随年龄的下降。
