Rikke Brad A, Yerg John E, Battaglia Matthew E, Nagy Tim R, Allison David B, Johnson Thomas E
Institute for Behavioral Genetics, University of Colorado at Boulder, USA.
J Gerontol A Biol Sci Med Sci. 2004 Feb;59(2):118-25. doi: 10.1093/gerona/59.2.b118.
Dietary restriction (DR) retards aging and mortality across a variety of taxa. In homeotherms, one of the hallmarks of DR is lower mean body temperature (T(b)), which might be directly responsible for some aspects of DR-mediated life extension. We conducted a quantitative trait locus (QTL) analysis of the response of T(b) to DR in mice using a panel of 22 LSXSS recombinant inbred strains, tested in two cohorts. T(b) in response to DR had a significant genetic component, explaining approximately 35% of the phenotypic variation. We mapped a statistically significant QTL to chromosome 9 and a provisional QTL to chromosome 17, which together accounted for about two thirds of the genetic variation. Such QTLs could be used to critically test whether the response of T(b) to DR also affects the response of life extension. In addition, this study demonstrates the feasibility of trying to map QTLs that affect other physiological responses to DR, including the life extension response. Importantly, the genes underlying such QTLs would be causal factors affecting these responses and could be identified by positional cloning.
饮食限制(DR)可延缓多种生物分类的衰老并降低死亡率。在恒温动物中,饮食限制的一个标志是平均体温(T(b))较低,这可能直接导致了饮食限制介导的寿命延长的某些方面。我们使用一组22个LSXSS重组近交系小鼠,在两个队列中进行测试,对小鼠T(b)对饮食限制的反应进行了数量性状基因座(QTL)分析。T(b)对饮食限制的反应具有显著的遗传成分,约占表型变异的35%。我们将一个具有统计学意义的QTL定位到9号染色体,并将一个临时QTL定位到17号染色体,它们共同占遗传变异的约三分之二。此类QTL可用于严格检验T(b)对饮食限制的反应是否也会影响寿命延长的反应。此外,本研究证明了尝试定位影响对饮食限制的其他生理反应(包括寿命延长反应)的QTL的可行性。重要的是,此类QTL背后的基因将是影响这些反应的因果因素,可通过定位克隆来识别。