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

人们早就知道，环境因素，如不良饮食，会对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不利影响，这种可能性直到最近才被提出。生理年龄相同的个体在衰老速度上差异很大。然而，令人惊讶的是，我们对生物衰老的可遗传率知之甚少，也不知道父母的状态如何“延续”影响后代的衰老，甚至在几代人身上积累，从而降低种群的适应性和适应潜力。最近的研究表明，“亲代效应”很常见，而且可能是实质性的，但它们对衰老的影响尚未被探索。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，研究跨代效应对细胞衰老（生物体细胞的生物学状况）的强度和影响，以及这种影响对野外个体衰老和健康的影响。在此，我们将调查影响父母状态的关键因素（例如年龄，遗传多样性，领土质量，疟疾感染）如何促成这种跨代影响。将测量线粒体数量和端粒长度，以评估生物衰老过程中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缩短有关。重要的是，线粒体基因具有高突变率，随年龄增长和氧化应激反应而增加。由于它们也是非重组和母系遗传的，它们很容易受到世代突变积累的影响。相反，端粒遗传是核遗传和双亲遗传，有趣的是，端粒在精子中可能随着父亲年龄的增长而增加。这些因素的不同遗传创造了遗传和亲代影响在雄性和雌性谱系中可能不同的可能性，并为我们提供了评估这种性别特异性影响的能力。这项研究将测量生物老化速率的变化有多少可以用“遗传质量”和“亲代状态”来解释，并调查在野外的多代中选择是如何作用于这些特征的。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，对整个孤立的塞舌尔林莺种群的长期研究现在提供了一个极好的机会，因为；我们有这个种群强大的、经过基因验证的多代血统。在鸟类的一生中重复采集血液样本，可以测量端粒和线粒体的个体变化率（大约3500个样本）。生存、繁殖力和年龄数据不受分散影响，这在自然系统中极为罕见。成年人缺乏天敌，因此衰老过程可以在没有过多的外在死亡率的情况下进行研究，从而减少样本量和混淆结果。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影响的驱动因素。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。它们还将帮助我们理解在自然界中观察到的物种之间和物种内部在寿命和衰老方面的巨大差异，使我们能够理解形成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.