Longer life spans and delayed maturation in wild-derived mice
Longer life spans and delayed maturation in wild-derived mice
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DOI：
10.1177/153537020222700715
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发表时间：
2002-07-01
影响因子：
3.2
通讯作者：
Austad, SN
中科院分区：
文献类型：
--
作者：
Miller, RA;Harper, JM;Austad, SN
几乎所有用于衰老研究的实验小鼠都来自经过多代选择以适应实验室饲养条件的谱系，随后进行近交。为了了解近亲繁殖和实验室适应是否改变了影响寿命的基因频率，我们从野生捕获的祖先中培育了三个品系的小鼠（爱达荷州[Id]、波恩佩[Po]和马朱罗[Ma]），并将它们与代表实验室适应基因库的遗传异质性小鼠种群（DC）进行了比较。平均寿命的Id股票超过了DC股票的24%（P < 0.00002），最大寿命，估计为平均寿命最长的10%的小鼠，也增加了16%（P < 0.003）。Ma原种小鼠的最长寿命也显著长于DC小鼠（9%，P = 0.04）。最长寿的Id小鼠在1450天时死亡，这似乎超过了之前完全喂养的非突变小鼠的寿命记录。Po小鼠的生命表与DC对照组相似。Ma和Id小鼠在几个方面与DC小鼠不同：两者都更短，更轻，两种种群的雌性，特别是Id，达到性成熟要慢得多。作为年轻的成年人，与DC对照组相比，Id小鼠具有较低水平的胰岛素样生长因子1（IGF-I）、瘦素和糖化血红蛋白，这暗示了几种生化途径是潜在的长寿介质。这些结果支持了这样一种观点，即在实验室小鼠的普通种群适应过程中，对快速成熟和大体型的无意选择可能迫使延迟衰老过程的天然等位基因的丢失。Id和Ma库存中存在的基因可能是有价值的工具，用于分析小鼠衰老的生理和生物化学。
Nearly all the experimental mice used in aging research are derived from lineages that have been selected for many generations for adaptation to laboratory breeding conditions and are subsequently inbred. To see if inbreeding and laboratory adaptation might have altered the frequencies of genes that influence life span, we have developed three lines of mice (Idaho [Id], Pohnpei [Po], and Majuro [Ma]) from wild-trapped progenitors, and have compared them with a genetically heterogeneous mouse stock (DC) representative of the laboratory-adapted gene pool. Mean life span of the Id stock exceeded that of the DC stock by 24% (P < 0.00002), and maximal life span, estimated as mean longevity of the longest-lived 10% of the mice, was also increased by 16% (P < 0.003). Mice of the Ma stock also had a significantly longer maximal longevity than DC mice (9%, P = 0.04). The longest-lived Id mouse died at the age of 1450 days, which appears to exceed the previous longevity record for fully fed, non-mutant mice. The life table of the Po mice resembled that of the DC controls. Ma and Id mice differ from DC mice in several respects: both are shorter and lighter, and females of both stocks, particularly Id, are much slower to reach sexual maturity. As young adults, Id mice have lower levels of insulin-like growth factor 1 (IGF-I), leptin, and glycosylated hemoglobin compared with DC controls, implicating several biochemical pathways as potential longevity mediators. The results support the idea that inadvertent selection for rapid maturation and large body size during the adaptation of the common stocks of laboratory mice may have forced the loss of natural alleles that retard the aging process. Genes present in the Id and Ma stocks may be valuable tools for the analysis of the physiology and biochemistry of aging in mice.