Understanding determinants of individual variation in senescence in a natural population

随着个人年龄的增长，他们的身体会退化--从细胞到全身--这一过程被称为衰老。很明显，每个人在开始衰老的年龄以及随后恶化的速度上存在很大的差异。例如，一项对38岁人类的研究报告了从28岁到61岁的生物年龄(即对个人内在条件/健康的衡量，而不是他们活了多长时间)。然而，为什么每个人的衰老差异如此之大，仍然没有答案。事实上，这是进化生物学中最大的悬而未决的问题之一。这对健康和(我们的老龄化)社会产生了巨大的影响，因为个人/人口可以减少对衰老产生负面影响的因素的暴露，从而使个人能够活得更健康，更不用说对动物繁殖和保护的相关影响(见学术受益者部分)。人们对衰老的个体差异的关注有限，没有足够的适当数据来衡量衰老的遗传成分，以及在自然种群中缺乏综合研究，在自然种群中，环境因素不同，自然选择和性别选择发挥作用，这阻碍了人们理解衰老的个体差异。这几点很重要。不同的特征(例如生殖能力、免疫防御、身体状况)可能会以不同的方式衰老，而个体基因构成的差异可能会支持不同的个体反应。一个人出生时父母的年龄也可能影响个人的衰老，或者生命早期的生育可能会影响晚年的生育能力。至关重要的是，在自然种群中，环境和社会效应将共同决定个体遭受的压力，影响遗传变异的表达，并最终影响个体的退化。在我们能够减轻有害因素的影响之前，我们需要了解这些因素对衰老的相对贡献。我们的目标是通过研究自然种群中个体衰老模式的相互作用的环境、社会、(非遗传)跨代和遗传决定因素来帮助弥补这些缺陷。我们现在才能做到这一点，因为我们从对合作繁殖的塞舌尔林莺种群的详细研究中获得了独特的长期数据来源。至关重要的是，这是一个与世隔绝的岛屿种群，这使得我们能够在他们的一生中跟踪所有个人(跨越多代人)，收集血液样本(从而允许测量个人的遗传特征和内在生物标记物)，并测量同时存在的环境条件、社会经历和个人特征。我们将使用这些数据以无与伦比的准确性测量个体在衰老开始和速度方面的差异。我们将量化整个基因组中的环境、社会、跨代(即父母年龄)和遗传因素对个体随年龄退化的时间和速度的影响。我们将确定不同个体特征之间和/或个体生命不同部分之间的权衡是否决定了衰老的模式，以及是否有遗传基础。我们将量化选择对衰老的影响程度。最后，我们将确定环境、社会、跨代和遗传效应对个体衰老的总体相对影响。这项研究不仅将检验许多关键预测，这些预测将揭示个体衰老变异的直接原因，还将揭示衰老进化背后的根本原因。了解哪些因素会加剧衰老意味着我们可以潜在地避免这些因素或条件，这将对人类/兽医、社会和保护直接有用。

As individuals reach older ages their bodies deteriorate - at the cellular to whole body level - a process known as senescence. It is clear that individuals differ greatly in the age at which they start to senesce, and how quickly they then deteriorate. For example, a study of 38-year-old humans reported biological ages (i.e. a measure of the intrinsic condition / health of the individual rather than how long they have been alive) that varied from 28 to 61 years. However, why individuals senesce so differently remains unresolved. Indeed, this is one of the biggest unanswered questions in evolutionary biology. This has massive ramifications for health and (our ageing) society, as individuals/populations could reduce exposure to factors that negatively impact senescence so that individuals can live longer healthier lives, not to mention associated implications for animal breeding and conservation (see academic beneficiaries section).Understanding individual variation in senescence has been hampered by a focus on a limited number of characteristics, insufficient appropriate data to measure the genetic component of senescence, and a paucity of integrated studies in natural populations where environmental factors vary and natural and sexual selection act out. These points are important. Different characteristics (e.g. reproductive ability, immunological defences, physical condition) may senesce differently, and variation in the genetic makeup of individuals may underpin different individual responses. The age of an individual's parents when it was born may also impact upon individual senescence, or reproduction early in life may affect ability to reproduce later in life. Crucially, in natural populations, environmental and social effects will combine to determine the stresses that individuals suffer, influence the expression of genetic variation, and ultimately impact on individual deterioration. Before we can mitigate the effect of deleterious factors we need to understand the relative contribution of these factors on senescence.We aim to help remedy these shortcomings by investigating the interacting environmental, social, (non-genetic) transgenerational and genetic determinants of individual patterns of senescence in a natural population. We can only now do this because we have a unique long-term data resource from a detailed study of a population of cooperatively breeding Seychelles warblers, Acrocephalus sechellensis. Crucially, this is an isolated island population, which has allowed us to follow all individuals (over many generations) throughout their lives, collect blood samples (thus allowing individual genetic characteristics and intrinsic biomarkers to be measured) and measure concurrent environmental conditions, social experiences and individual characteristics.We will use these data to measure individual variation in the onset and rate of senescence with unparalleled accuracy. We will quantify the impact of environmental, social, transgenerational (i.e. parental age) and genetic factors, across the genome, on when and how quickly individuals deteriorate with age. We will establish if trade-offs between different individual characteristics, and/or across different parts of an individual's life, determine patterns of senescence and whether there is a genetic basis to this. We will quantify the strength of selection on senescence. Finally, we will determine the overall relative impact that environmental, social, transgenerational and genetic effects have on individual senescence.This study will not only test many key predictions that will reveal the immediate causes of individual variation in senescence, it will also shed light on the ultimate reasons behind the evolution of senescence. Understanding which factors exacerbate senescence means we can potentially avoid such factors or conditions, which will be directly useful to human/veterinary medicine, society and conservation.