Early-life environmental effects on ageing in an evolutionary context

进化背景下生命早期环境对衰老的影响

• 批准号: BB/H021868/1
• 负责人: Daniel Nussey
• 金额: $ 133万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH021868%2F1
• 关键词: Early; life; environmental; effects; ageing

There are currently more people aged over 65 than aged under 16 living in the UK. As the elderly compose an increasing proportion of our society, understanding the basic biology of ageing becomes an urgent priority. There is astonishing variation between individuals in both ageing rates and lifespan. Understanding the causes of this variation is central to long-standing hopes of alleviating or postponing the ageing process and meeting the challenges associated with an ageing population. In humans and other long-lived mammals, environmental conditions experienced during early life play an important role in determining health and mortality risk in adulthood. Epidemiological studies in humans show that individuals experiencing poor nutrition or infection during development or infancy have increased risk of ill health (e.g. heart disease, diabetes) and shortened life expectancy. Many researchers have suggested that these early-life environmental effects reflect developmental responses that evolved in our distant ancestors to allow individuals to grow up to 'match' their expected environment. Recently, there have been major advances in our understanding of the proximate physiological mechanisms linking a poor start in life with later health. However, understanding of the ultimate evolutionary mechanisms that have shaped developmental responses to the environment and their consequences for the ageing process in long-lived vertebrates has remained very limited. This is largely because modern humans and domestic and laboratory animals experience benign and protected environments that are not representative of the conditions in which life histories and ageing actually evolved. I will address this crucial gap in our knowledge by testing how natural selection has shaped individual responses to early-life environmental conditions in mammals, using a long-term study of wild Soay sheep on St Kilda. This study population represents a unique system in which to understand the evolution of ageing in nature. Individuals in this population experience a highly variable environment and have been the subject of extremely detailed individual-based monitoring since 1985. Repeated records on individual reproductive performance, body mass and parasite burden have already been collected over the lives of more than 5,000 animals. Blood samples collected at capture as part of the study provide a remarkable, but as yet untapped, resource to assay relevant biochemical and immunological markers associated with ageing. My overarching aim is to test and integrate evolutionary and physiological explanations for how and why early environmental conditions drive variation in ageing rates in the Soay sheep population. I will combine existing longitudinal data on environment and life history with new laboratory work using blood samples to measure immune responses and levels of cellular damage across the lifetimes of thousands of individual sheep I will use this data to address the hypothesis that developmental responses to poor nutrition or infection in early life represent 'predictive adaptive responses' that allow individuals to match their expected adult environment. I will also determine how natural selection acts on the physiological trade-offs between growth, reproduction, immune responses and physiological damage in a complex and variable natural environment. Ultimately, I will quantify how, when and why natural selection favours particular developmental and life history strategies and how this influences ageing rates and lifespan. The completed project will represent one of the most detailed longitudinal studies of the evolutionary and environmental causes of ageing ever undertaken outside of the laboratory. It will provide novel and timely tests of evolutionary predictions that could explain the effects of developmental environment, growth and infection in early life on ageing and health in later adulthood in long-lived mammals.

目前居住在英国的65岁以上的人比16岁以下的人多。随着老年人在我们社会中所占的比例越来越大，了解老龄化的基本生物学成为当务之急。在衰老速度和寿命方面，个体之间存在着惊人的差异。长期以来，人们一直希望缓解或延缓老龄化进程，并应对与人口老龄化相关的挑战，了解这种差异的原因至关重要。在人类和其他长寿哺乳动物中，生命早期经历的环境条件在决定成年期的健康和死亡风险方面发挥着重要作用。人类流行病学研究表明，在发育或婴儿期营养不良或受到感染的人，健康状况不佳（如心脏病、糖尿病）的风险增加，预期寿命缩短。许多研究人员认为，这些早期生活环境的影响反映了我们遥远的祖先进化出来的发育反应，使个体长大后能够“匹配”他们预期的环境。最近，我们对不良开端与后期健康之间联系的近似生理机制的理解取得了重大进展。然而，对于形成对环境的发育反应的最终进化机制及其对长寿脊椎动物衰老过程的影响的理解仍然非常有限。这在很大程度上是因为现代人、家养动物和实验动物所处的环境是良性的、受保护的，这些环境并不代表生活史和衰老实际进化的条件。我将通过对圣基尔达野生索伊羊的长期研究，测试自然选择如何影响哺乳动物对早期环境条件的个体反应，从而解决我们知识中的这一关键空白。这个研究群体代表了一个独特的系统，在这个系统中，我们可以了解自然界中衰老的演变。自1985年以来，这一人群中的个体经历了高度变化的环境，并一直是极其详细的基于个体的监测对象。已经收集了5000多只动物的个体繁殖性能、体重和寄生虫负担的重复记录。作为研究的一部分，捕获时收集的血液样本为测定与衰老相关的生化和免疫标志物提供了一种非凡的、但尚未开发的资源。我的首要目标是测试和整合进化和生理学的解释，以解释早期环境条件如何以及为什么会导致Soay羊种群的衰老率变化。我将把现有的关于环境和生活史的纵向数据与新的实验室工作结合起来，使用血液样本来测量数千只绵羊个体一生中的免疫反应和细胞损伤水平。我将利用这些数据来解决这样一个假设，即早期对营养不良或感染的发育反应代表了“预测性适应性反应”，允许个体匹配其预期的成年环境。我还将确定自然选择如何在复杂多变的自然环境中对生长、繁殖、免疫反应和生理损伤之间的生理权衡起作用。最后，我将量化自然选择如何、何时以及为什么偏爱特定的发育和生活史策略，以及这如何影响老龄化速度和寿命。完成的项目将是在实验室之外对衰老的进化和环境原因进行的最详细的纵向研究之一。它将为进化预测提供新颖和及时的测试，这些预测可以解释早期的发育环境、生长和感染对长寿哺乳动物成年后的衰老和健康的影响。

项目成果

Plasma markers of oxidative stress are uncorrelated in a wild mammal.

• DOI: 10.1002/ece3.1771
• 发表时间: 2015-11
• 期刊: Ecology and evolution
• 影响因子: 2.6
• 作者: Christensen LL;Selman C;Blount JD;Pilkington JG;Watt KA;Pemberton JM;Reid JM;Nussey DH
• 通讯作者: Nussey DH

Lifelong leukocyte telomere dynamics and survival in a free-living mammal.

终生的白细胞端粒动力学和自由哺乳动物中的生存。

• DOI: 10.1111/acel.12417
• 发表时间: 2016-02
• 期刊: Aging cell
• 影响因子: 7.8
• 作者: Fairlie J;Holland R;Pilkington JG;Pemberton JM;Harrington L;Nussey DH
• 通讯作者: Nussey DH

Contrasting drivers of reproductive ageing in albatrosses.

• DOI: 10.1111/1365-2656.12712
• 发表时间: 2017-09
• 期刊: The Journal of animal ecology
• 作者: Froy H;Lewis S;Nussey DH;Wood AG;Phillips RA
• 通讯作者: Phillips RA

Marker-dependent associations among oxidative stress, growth and survival during early life in a wild mammal.

• DOI: 10.1098/rspb.2016.1407
• 发表时间: 2016-10-12
• 期刊: Proceedings. Biological sciences
• 作者: Christensen LL;Selman C;Blount JD;Pilkington JG;Watt KA;Pemberton JM;Reid JM;Nussey DH
• 通讯作者: Nussey DH

Age-related variation in foraging behaviour in the wandering albatross at South Georgia: no evidence for senescence.

• DOI: 10.1371/journal.pone.0116415
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Froy H;Lewis S;Catry P;Bishop CM;Forster IP;Fukuda A;Higuchi H;Phalan B;Xavier JC;Nussey DH;Phillips RA
• 通讯作者: Phillips RA