Dietary restriction of rodents decreases aging rate without affecting initial mortality rate a meta-analysis
Dietary restriction of rodents decreases aging rate without affecting initial mortality rate a meta-analysis
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DOI：
10.1111/acel.12061
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发表时间：
2013-06-01
期刊：
影响因子：
7.8
通讯作者：
Verhulst, Simon
中科院分区：
文献类型：
--
作者：
Simons, Mirre J. P.;Koch, Wouter;Verhulst, Simon
饮食限制（DR）延长了来自不同分类群的多个物种的寿命。这种影响可以通过两种不同但不相互排斥的方式产生：衰老率的变化和/或对衰老过程的脆弱性（即初始死亡率）。当DR影响脆弱性时，这会立即降低死亡率，而老龄化率的变化将随着时间的推移逐渐降低死亡风险。揭示DR如何延长寿命是有意义的，因为它可以指导理解介导寿命延长的机制，也对DR的应用具有实际意义。我们通过拟合Gompertz和GompertzMakeham模型，重新分析了大鼠和小鼠DR实验中82对生存曲线的已发表生存数据。据报道，增加的Makeham参数，以改善Gompertz参数的估计。这两个模型都将初始死亡率（脆弱性）与死亡率随年龄增长而增加（老龄化率）分开。我们对获得的Gompertz参数进行了荟萃分析。我们发现，DR降低了老化率，而不影响脆弱性。后者与最近对一个大部分重叠的数据集进行分析的结论形成对比，我们展示了早期的发现是如何归因于统计伪影的。我们的分析表明，生物学基础的寿命延长作用的DR在啮齿类动物可能涉及衰减积累的损害，这与急性效应的DR对死亡率的果蝇报道。此外，我们的研究结果表明，经常报告的老龄化率和脆弱性之间的相关性并没有限制不断变化的老龄化率，而不同时影响脆弱性。
Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, whereas a change in aging rate will gradually lower mortality risk over time. Unraveling how DR extends lifespan is of interest because it may guide toward understanding the mechanism(s) mediating lifespan extension and also has practical implications for the application of DR. We reanalyzed published survival data from 82 pairs of survival curves from DR experiments in rats and mice by fitting Gompertz and also GompertzMakeham models. The addition of the Makeham parameter has been reported to improve the estimation of Gompertz parameters. Both models separate initial mortality rate (vulnerability) from an age-dependent increase in mortality (aging rate). We subjected the obtained Gompertz parameters to a meta-analysis. We find that DR reduced aging rate without affecting vulnerability. The latter contrasts with the conclusion of a recent analysis of a largely overlapping data set, and we show how the earlier finding is due to a statistical artifact. Our analysis indicates that the biology underlying the life-extending effect of DR in rodents likely involves attenuated accumulation of damage, which contrasts with the acute effect of DR on mortality reported for Drosophila. Moreover, our findings show that the often-reported correlation between aging rate and vulnerability does not constrain changing aging rate without affecting vulnerability simultaneously.