A model for antagonistic pleiotropic gene action for mortality and advanced age.
A model for antagonistic pleiotropic gene action for mortality and advanced age.
复制标题
对抗性多效性基因对死亡率和高龄作用的模型。
DOI：
--
复制
发表时间：
1998
影响因子：
9.8
通讯作者：
François Schächter
中科院分区：
文献类型：
--
作者：
Bruno Toupance;Bernard Godelle;Bernard Godelle;P. Gouyon;François Schächter
涉及控制和长寿人群的关联或连锁研究提供了影响长寿的基因信息。然而，存活率的等位基因特异性差异与衰老队列的遗传结构之间的关系仍不清楚。我们建立了一个异质性队列模型，该队列包括几种不同年龄特异性死亡率的基因型。在其最一般的形式，没有任何具体的假设，关于死亡率曲线的形状，该模型允许推导出一个基本属性的突然年龄相关的变化，在一个队列的组成。该模型适用于特定性别的生存曲线，从周期生命表，Gompertz-Makeham死亡率系数计算法国人口。然后，根据Gompertz-Makeham死亡率函数进行调整，组成一个异质性队列的三种基因型，约束下拟合得到的死亡率的真实的法国人口死亡率从生命表。第八个十年后的多峰曲线和发散出现的频率轨迹的经常性特征。最后，一个适合以前获得的数据在血管紧张素转换酶位点实现，解释了什么似乎是矛盾的结果，即，基因型的频率被称为心血管疾病的危险因素是在百岁老人增加。我们的研究结果有助于解释有据可查的偏离Gompertz-Makeham死亡率动力学在老年。我们的模型的影响进行了讨论的背景下，已知的遗传效应对人类寿命和年龄相关的病理。由于早期和晚期生存之间的拮抗多效性作为一般规则出现，因此将特定年龄组中的基因测量的影响外推到其他年龄可能会产生误导。
Association or linkage studies involving control and long-lived populations provide information on genes that influence longevity. However, the relationship between allele-specific differences in survival and the genetic structure of aging cohorts remains unclear. We model a heterogeneous cohort comprising several genotypes differing in age-specific mortality. In its most general form, without any specific assumption regarding the shape of mortality curves, the model permits derivation of a fundamental property underlying abrupt age-related changes in the composition of a cohort. The model is applied to sex-specific survival curves taken from period life tables, and Gompertz-Makeham mortality coefficients are calculated for the French population. Then, adjustments are performed under Gompertz-Makeham mortality functions for three genotypes composing a heterogeneous cohort, under the constraint of fitting the resultant mortality to the real French population mortality obtained from life tables. Multimodal curves and divergence after the 8th decade appear as recurrent features of the frequency trajectories. Finally, a fit to data previously obtained at the angiotensin-converting-enzyme locus is realized, explaining what had seemed to be paradoxical results-namely, that the frequency of a genotype known as a cardiovascular risk factor was increased in centenarians. Our results help explain the well-documented departure from Gompertz-Makeham mortality kinetics at older ages. The implications of our model are discussed in the context of known genetic effects on human longevity and age-related pathologies. Since antagonistic pleiotropy between early and late survival emerges as a general rule, extrapolating the effects measured for a gene in a particular age class to other ages could be misleading.
登录
查看更多内容
影响因子：
56.9
作者：
JOHNSON, TE
通讯作者：
JOHNSON, TE
地中海果蝇死亡率的组成解释。
DOI：
10.1126/science.8503016
发表时间：
1993
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Vaupel,JW;Carey,JR
通讯作者：
Carey,JR
影响因子：
56.9
作者：
CURTSINGER, JW;FUKUI, HH;VAUPEL, JW
通讯作者：
VAUPEL, JW
影响因子：
56.9
作者：
CAREY, JR;LIEDO, P;VAUPEL, JW
通讯作者：
VAUPEL, JW