Heritability of the rate of ageing: novel statistics and models to quantify ageing

生物体为什么以及如何衰老并最终死亡？这是生物学中尚未解决的大问题之一，也是人类关注的医学圣杯。传统上，衰老是在生理学和医学领域内研究的;由于鸟类和哺乳动物野生种群中令人信服的衰老证据，衰老已被纳入生态学和进化。此外，在野外，生理性能随着年龄的增长而下降（生殖和父母照顾减少），端粒缩短（衰老的生物标志物），存活率随着年龄的增长而下降。为了让我们现在了解衰老的演变及其潜在的生理机制，我们必须将衰老过程中的环境效应和遗传效应分开。此外，死亡率的人口统计学分析可以使用统计学划分潜在的生理机制。死亡记录的人口统计学尽可能接近实际死亡的生物学特征，并揭示了两个主要组成部分：随着年龄增长而增加的死亡风险-老龄化率-和脆弱性-易因老龄化相关原因死亡。该提案旨在开发一种新的统计方法来估计这两个人口统计特性的环境和遗传效应。我们的团队还研究了理想的种群，以随后测试环境和遗传对衰老率和脆弱性的影响：我们已经监测了14年以上的伦迪岛上的家雀种群，我们已经使用DNA指纹分析得出了完整的谱系（谁与谁有关）。此外，我们的目标是测试我们开发的第一个理论模型的环境对脆弱性的影响，与当前的衰老理论模型不可调和，以进一步增加我们对导致衰老的机制以及如何减缓衰老的理解。这要归功于我们提议的国际合作伙伴Marc Tatar教授（美国布朗大学）的开创性工作。Tatar进行了第一个也是唯一一个估计衰老率和脆弱性（都在昆虫中）遗传性的研究，开创了统计学来解开这些因素，他的实验室拥有独特的技能和工具来评估测试拟议的脆弱理论模型所需的详细人口统计学。

Why and how do organisms age and ultimately die? This is one of the big unsolved questions in biology, and when humans are concerned the Holy Grail of medical science. Traditionally ageing has been studied within the realm of physiology and medicine; senescence has been incorporated into ecology and evolution due to compelling evidence of ageing in wild populations of birds and mammals. Also, in the wild, physiological performance reduces with age (reproduction and parental care reduce), telomeres shorten (a biomarker of aging) and survival decreases with age. For us to now understand the evolution of ageing and its underlying physiological mechanisms we must separate environmental effect and genetic effects on the ageing process. In addition, demographic analysis of mortality can partition the underlying physiological mechanisms using statistics. Demography of death records is as close to the biology of actual death as possible and reveals two main components: the increasing risk of death with age - ageing rate - and frailty - the vulnerability to death from ageing-related causes. This proposal seeks to develop a novel statistical approach to estimate environmental and genetic effects in these two demographic properties. Our group also studies the ideal population to subsequently test for environmental and genetic effects on ageing rate and frailty: the house sparrow population on Lundy island which we have monitored for over 14 years and for which we have worked out the complete pedigree (who-is-related to whom) using DNA fingerprinting. In addition we aim to test the first theoretical model we developed of environmental effects on frailty, irreconcilable with current theoretical models of ageing to further increase our understanding of the mechanisms that cause ageing and how we could slow it down. This is possible thanks to the pioneering work of our proposed international partner, Prof Marc Tatar (Brown University, USA). Tatar conducted the first and only studies that have estimated the heritability of ageing rate and frailty (both in insects), has pioneered the statistics to disentangle these factors, and his lab has the unique skills and tools in place to assess the detailed demography needed to test the proposed theoretical model of frailty.