Transgenerational impacts on senescence: quantitative genetics of cellular and organismal ageing in the wild

人们早就知道，环境因素，如不良的饮食习惯，会对一个人的衰老速度产生相当大的影响，然而，这些影响可能会传递给下一代，对后代甚至后代的衰老产生心理影响，直到最近才有人提出。相同实足年龄的个体在生物学上衰老的速度有很大差异。然而，令人惊讶的是，我们对生物衰老的速度有多遗传知之甚少，也不知道父母的状态如何“延续”来影响后代的衰老--甚至在几代人之间积累起来，降低种群的适应性和适应潜力。最近的研究表明，“父母的影响”是常见的，可以是实质性的，但他们对衰老的影响还没有被探讨。我们建议在生态环境中整合细胞生物学和定量遗传学的方法，以研究跨代效应对细胞衰老（生物体细胞的生物学条件）的强度和影响，以及这种影响对个体衰老和野外健身的后果。在此范围内，我们将研究影响父母状态的关键因素（如年龄，遗传多样性，领土质量，疟疾感染）如何促成这种跨代效应。线粒体数量和端粒长度将被测量，以评估生物老化的个体间和个体内的差异。端粒和线粒体的丢失与细胞和有机体衰老的增加以及预期寿命的减少有关。重要的是，线粒体基因具有高突变率，随着年龄的增长和对氧化应激的反应而增加。由于它们也是非重组的和母系遗传的，它们很容易受到跨代突变积累的影响。相比之下，端粒遗传是核遗传和双亲遗传，有趣的是，精子中的端粒长度可能会随着父亲年龄的增长而增加。这些因素的不同遗传造成的可能性，遗传和父母的影响可能不同，通过男性和女性线，并为我们提供了评估这种性别特异性的影响的能力。这项研究将测量生物衰老率的变化有多少是由“遗传质量”和“亲本状态”解释的，并调查选择如何在野外多代中对这些性状起作用。这种纵向研究以前不可能在自由生活的脊椎动物中进行，因为它们的寿命很长，而且缺乏研究细胞衰老的技术。然而，长期研究的整个，孤立的，人口塞舌尔莺现在提供了一个很好的机会，因为这样做;1。我们有一个强大的，经过基因验证的，多代血统的人口2。在鸟类的整个生命周期中重复采集血液样本，以测量端粒和线粒体变化的个体速率（约100）。3，500个样本）。3.生存，繁殖力和年龄数据是不混淆的扩散，这是非常罕见的自然系统4。成虫缺乏天敌，因此可以研究衰老过程，而不会有过多的外在死亡率，从而减少样本量和混淆结果5。我们有关于遗传和环境因素的广泛详细的个人信息，使我们能够分离出父母效应的驱动因素这项新研究的研究结果将有助于确定父母在衰老模式方面对后代生活的影响。它们还将帮助我们了解自然界中物种之间和物种内部观察到的长寿和衰老的非凡变化，使我们能够了解塑造衰老进化的基本因素。

It has long been known that environmental factors, such as poor diet, can have considerable impact on an individuals' rate of ageing, however the possibility that these effects could be transmitted to the next generation, detrimentally impacting on ageing in offspring, or even grand offspring, has only recently been suggested.Individuals of the same chronological age vary greatly in the rate at which they age biologically. Yet surprisingly we know little about how heritable the rate of biological ageing is, or how parental state can "carry-over" to influence offspring ageing - and even accumulate over generations to reduce population fitness and adaptive potential. Recent studies show that 'parental effects' are common and can be substantial, but the impact they have on senescence has not been explored. We propose to integrate approaches from cellular biology and quantitative genetics, in an ecological setting, to investigate the strength and impact of trans-generational effects on cellular senescence (the biological condition of an organisms cells) - and the consequences of this for individual ageing and fitness in the wild. Within this we will investigate how key factors effecting parental state (e.g. age, genetic diversity, territory quality, malarial infection) contribute towards such trans-generational effects.Mitochondria number and telomere length will be measured to assess inter and intra-individual variation in biological ageing. The loss of both telomeres and mitochondria is related to an increase in cellular and organismal senescence and a reduction in life expectancy. Importantly, mitochondrial genes have high mutation rates, which increase with age and in response to oxidative stress. As they are also non-recombinant and maternally inherited, they are vulnerable to the accumulation of mutations across generations. In contrast, telomere inheritance is nuclear and bi-parentally inherited and, intriguingly, telomeres may increase in length, in sperm, with paternal age. The different inheritance of these factors creates the possibility that genetic and parental effects may differ through the male and female line, and provides us with the ability to assess such sex-specific effects. This study will measure how much variation in biological ageing rate is explained by "genetic quality" and "parental state" - and investigate how selection acts upon these traits over multiple generations in the wild. Such longitudinal studies have not previously been possible in free-living vertebrates, given their long life-spans and the lack of techniques with which to investigate cellular senescence. However, the long-term study of an entire, isolated, population of Seychelles warblers now provides an excellent opportunity to do so because;1. We have a powerful, genetically verified, multi-generational pedigree for this population2. Repeat blood samples taken throughout the birds' lives allow for individual rates of telomere and mitochondrial change to be measured (ca. 3,500 samples).3. Survival, fecundity and age data are unconfounded by dispersal, which is extremely rare in natural systems4. Adults lack natural predators, thus ageing processes can be studied without excessive extrinsic mortality reducing sample size and confounding results5. We have extensive detailed individual information on genetic and environmental factors, allowing us to isolate drivers of parental effectsThe research outcomes from this novel study will help identify the effect parents have, in terms of senescence patterns, on the lives of their offspring. They will also help us understand the extraordinary variation in longevity and senescence observed between and within species in nature allowing us to understand the fundamental factors shaping the evolution of senescence.