Does caloric restriction extend life in wild mice?
Does caloric restriction extend life in wild mice?
复制标题
DOI：
10.1111/j.1474-9726.2006.00236.x
复制
发表时间：
2006-12-01
期刊：
影响因子：
7.8
通讯作者：
Austad, Steven N.
中科院分区：
文献类型：
--
作者：
Harper, James M.;Leathers, Charles W.;Austad, Steven N.
为了研究经过多代实验室选择的遗传未改变的小鼠是否表现出与实验室啮齿动物相似的激素和人口统计学反应，我们对遗传异质性雄性小鼠的队列进行了CR，这些雄性小鼠是野生捕获祖先的后代。虽然激素的变化，特别是皮质酮的增加和睾酮的减少，模仿实验室适应的啮齿动物中看到的，我们发现没有差异的平均寿命之间的随意（AL）和CR饮食组，虽然最大似然拟合Gompertz死亡率模型表明一个显着较浅的斜率和较高的截距CR组。这一结果是由于CR动物在生命早期的死亡率较高，但在生命晚期的死亡率较低。一部分动物可能表现出对CR的标准人口统计学反应，因为我们最长寿的8.1%的动物都来自CR组。尽管各组之间缺乏明显的平均寿命差异，但我们确实注意到CR在实验室啮齿动物中观察到的强烈抗癌作用。我们的结果有三种合理的解释：（1）在实验室条件下未选择的动物不显示典型的CR效应;（2）因为野生动物在喂食AL时吃得较少，我们的限制方案太严格而看不到CR效应;或（3）野生种群中存在CR效应的遗传变异;在实验室驯化条件下，不经意地选择了对CR有延长寿命应答的变体。
To investigate whether mice genetically unaltered by many generations of laboratory selection exhibit similar hormonal and demographic responses to caloric restriction (CR) as laboratory rodents, we performed CR on cohorts of genetically heterogeneous male mice which were grandoffspring of wild-caught ancestors. Although hormonal changes, specifically an increase in corticosterone and decrease in testosterone, mimicked those seen in laboratory-adapted rodents, we found no difference in mean longevity between ad libitum (AL) and CR dietary groups, although a maximum likelihood fitted Gompertz mortality model indicated a significantly shallower slope and higher intercept for the CR group. This result was due to higher mortality in CR animals early in life, but lower mortality late in life. A subset of animals may have exhibited the standard demographic response to CR in that the longest-lived 8.1% of our animals were all from the CR group. Despite the lack of a robust mean longevity difference between groups, we did note a strong anticancer effect of CR as seen in laboratory rodents. Three plausible interpretations of our results are the following: (1) animals not selected under laboratory conditions do not show the typical CR effect; (2) because wild-derived animals eat less when fed AL, our restriction regime was too severe to see the CR effect; or (3) there is genetic variation for the CR effect in wild populations; variants that respond to CR with extended life are inadvertently selected for under conditions of laboratory domestication.