Dietary restriction and the pursuit of effective mimetics
Dietary restriction and the pursuit of effective mimetics
复制标题
饮食限制和追求有效的模仿
DOI：
10.1017/s0029665113003832
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发表时间：
2014
影响因子：
7
通讯作者：
Selman C
中科院分区：
文献类型：
--
作者：
Selman C
饮食限制 (DR) 已被证明可以延长一系列动物的中位寿命和最大寿命，尽管最近的研究结果表明，并非所有动物都普遍享有这些效果。特别是，小鼠 DR 后的寿命影响具有高度品系特异性，目前几乎没有证据表明 DR 对非人类灵长类动物的全因死亡率产生积极影响。然而，DR 对健康的积极影响似乎在绝大多数物种（包括人类受试者）中高度保守。尽管对健康有这些影响，但考虑到所需的克制程度，DR 不太可能成为大多数人类受试者现实或流行的生活选择。因此，重要的研究重点是确定能够带来 DR 益处的化合物，而无需严格减少每日食物摄入量。几种此类化合物，包括雷帕霉素、二甲双胍和白藜芦醇，已被确定为潜在的 DR 模拟物。尽管这些化合物显示出巨大的前景，但仍需要正确理解这些药物的作用机制。本综述将讨论了解遗传背景和异质性在调节 DR 的寿命和健康寿命影响中所起的作用的重要性。它还将概述当前最有前途的 DR 模拟物及其对健康寿命的影响。
Dietary restriction (DR) has been shown to extend both median and maximum lifespan in a range of animals, although recent findings suggest that these effects are not universally enjoyed across all animals. In particular, the lifespan effect following DR in mice is highly strain-specific and there is little current evidence that DR induces a positive effect on all-cause mortality in non-human primates. However, the positive effects of DR on health appear to be highly conserved across the vast majority of species, including human subjects. Despite these effects on health, it is highly unlikely that DR will become a realistic or popular life choice for most human subjects given the level of restraint required. Consequently significant research is focusing on identifying compounds that will bestow the benefits of DR without the obligation to adhere to stringent reductions in daily food intake. Several such compounds, including rapamycin, metformin and resveratrol, have been identified as potential DR mimetics. Although these compounds show significant promise, there is a need to properly understand the mechanisms through which these drugs act. This review will discuss the importance in understanding the role that genetic background and heterogeneity play in mediating the lifespan and healthspan effects of DR. It will also provide an overview of the most promising current DR mimetics and their effects on healthy lifespan.