Understanding determinants of individual variation in senescence in a natural population

了解自然群体中衰老个体差异的决定因素

基本信息

批准号：
NE/P011284/1
负责人：
Amanda Bretman
金额：
$ 64.24万
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FP011284%2F1
关键词：
Understanding determinants individual variation senescence

项目摘要

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.

随着个体年龄的增长，身体的年龄会恶化 - 在细胞到整个身体水平上 - 一种称为衰老的过程。很明显，个人在开始参议院的年龄以及随后变速后的速度有多差异。例如，一项对38岁人类的研究报告了生物学年龄（即对个体的内在状况 /健康，而不是他们活着的时间的衡量），范围从28到61岁不等。但是，为什么个人如此不同地持有分歧。确实，这是进化生物学中最大的未解决问题之一。这对健康和（我们的老龄化）社会产生了巨大影响，因为个人/人口可以减少对衰老产生负面影响的因素，从而使个人生活更长的健康生活，更不用说对动物育种和保护的相关影响（请参阅学术受益人部分）。理解衰老的个体变化受到关注有限的特征，不足的数据来衡量衰老的遗传成分以及在自然种群中的综合研究很少，在这种自然群体中，环境因素改变与自然和性选择性。出去。这些要点很重要。不同的特征（例如生殖能力，免疫防御能力，身体状况）可能会有所不同，并且个体的遗传组成的变化可能会支持不同的个体反应。一个人的父母出生时的年龄也可能会对个体衰老或生命早期繁殖影响，可能会影响以后再现的能力。至关重要的是，在自然人群中，环境和社会影响将结合起来，以确定个人遭受的压力，影响遗传变异的表达，并最终影响个人恶化。在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。我们的目的是通过研究相互作用的环境，社会，（非基因）跨代和遗传决定因素来帮助解决这些缺点。自然人口的衰老。我们之所以能够这样做，是因为我们从详细的研究中获得了独特的长期数据资源，该研究对合作繁殖的塞舌尔莺（Acrocephalus sechellensis）进行了详细研究。至关重要的是，这是一个孤立的岛屿人口，它使我们能够一生跟随所有个人（几代人），收集血样（从而允许衡量个体的遗传特征和内在的生物标志物）并衡量并发的环境条件，社会经验我们将使用这些数据以无与伦比的精度来衡量衰老的发作和衰老率的个体变化。我们将量化环境，社会，跨代（即父母年龄）和遗传因素，基因组，何时何时何地随着年龄的年龄恶化的速度，对环境，社会，跨代年龄（即父母年龄）和遗传因素的影响。我们将确定在不同的个人特征和/或个人生活的不同部分之间的权衡，决定了衰老的模式以及是否存在遗传基础。我们将量化衰老时选择的强度。最后，我们将确定环境，社会，跨代和遗传效应对个别衰老的总体相对影响。这项研究不仅会检验许多关键预测，这些预测将揭示出衰老中个体变化的直接原因，还将阐明它。衰老演变的最终原因。了解哪些因素加剧了衰老，这意味着我们可以避免这种因素或条件，这将直接对人类/兽医医学，社会和保护直接有用。