Male ageing and the ejaculate: composition, competition and conflict

父母正在变老。在英国、美国和其他发达国家，人们晚育是一种趋势，随之而来的是一系列潜在的困难。对妇女来说，许多困难相对来说是众所周知的：更年期有时间限制，生育能力随着年龄的增长而下降，大龄母亲的孩子患遗传疾病的机会增加。但鲜为人知的是，男性也有“生物钟”；精子质量和生育能力随着年龄的增长而下降，老年男子的子女患某些遗传疾病的可能性也会增加。衰老的这些影响不仅适用于人类，而且可能在动物王国中无处不在。目前有大量的研究，在模式生物，如苍蝇和老鼠，帮助我们了解衰老的基本生物学和进化，导致它的基因和分子，以及我们如何开发干预措施，以减缓衰老和促进健康的人。伴随这类研究而来的是对女性生殖衰老的见解。这是因为女性的生殖老化是显而易见的：随着年龄的增长，女性通常会生育更少的后代，这很容易量化。然而，男性的生殖老化则更为神秘。雄性后代是通过雌性繁殖的，因此在实验上更难测量。此外，有几个原因可以解释为什么雄性动物繁殖失败。例如，这可能是因为它们不交配，因为它们不能产生有效的精子或精液，或者因为它们即使交配也不能将射精输送给雌性。然而，利用果蝇（Drosophila melanogaster），现在有可能测量精液的许多方面，新的“蛋白质组学”技术意味着我们可以量化男性射精的整体成分。现在是利用这些技术的理想时机，以及我们对这个物种衰老生物学的广泛和不断增长的知识，来测试衰老是如何影响男性射精的，并探索射精老化的后果。这就是我项目的目标。在第一部分中，我将描述射精是如何随着男性年龄的增长而变化的。随着年龄的增长，男性产生的精子或精液会减少吗？精液的成分会改变吗？有多少会转移到雌性身上？我将研究各种重要因素如何影响老年男性射精，如营养、健康和交配活动。我还将测试延长寿命的干预措施，如饮食限制（在不挨饿的情况下减少食物摄入），或操纵参与营养感应途径的基因，是否能让衰老的男性更健康地射精。结合从这些实验中收集到的信息和进化理论，我将预测男性射精老化将如何影响女性的生育能力和生殖成功，以及男性之间精子竞争的结果。在项目的第二部分，我将测试进化理论，告诉我们男性衰老如何影响男性和女性的适应性生殖决策。例如，女性更适合与年轻男性还是年长男性交配？男性的精子竞争能力会随着年龄的增长而改变吗？通过基因操纵男性生殖蛋白，我将能够发现导致这种与年龄相关的变化的基因。该项目的目标是揭示与射精年龄相关的变化的重要性，是否可以做些什么来改善射精老化的负面影响，并帮助解释年龄介导的男性和女性做出的生殖决定。

Parents are becoming older. In the UK, the US and other developed countries, there is a trend for people to have children later, and with this trend comes a suite of potential difficulties. For women, many of these difficulties are relatively well known: there is a time limit imposed by the menopause, fertility declines with age and there are increased chances of genetic disorders in the children of older mothers. But less well known is that males also have a "biological clock"; sperm quality and fertility declines with age and the probability of certain genetic disorders in children of older men is also increased. These impacts of ageing don't just apply to humans but are likely ubiquitous across the animal kingdom. There is currently lots of research, in model organisms such as flies and mice, to help us understand the basic biology and evolution of ageing, the genes and molecules that cause it, and how we might develop interventions to slow ageing and promote health in people. Along with this type of research often comes insights into female reproductive ageing. This is because reproductive ageing in females is obvious: females often produce fewer offspring as they age and this is easy to quantify. Male reproductive ageing is, however, more cryptic. Male offspring-production occurs via females, so it is experimentally more challenging to measure. Moreover, there are several reasons why males might fail reproductively. For example, it could be because they don't mate, because they don't make effective sperm or seminal fluids, or because they fail to transfer ejaculates to females if they do mate. However, using the fruit fly, Drosophila melanogaster, it is now possible to measure many aspects of the semen, and new "proteomic" techniques mean that we can quantify the overall composition of the male ejaculate. Now is the ideal time to utilise these techniques, and our extensive and increasing knowledge about the biology of ageing in this species, to test how ageing impacts the male ejaculate and to explore the consequences of ejaculate ageing. This is what my project aims to do. In the first part, I will characterise how the ejaculate changes as males age. Do males produce fewer sperm or less seminal fluid, as they get older? Does the composition of the semen change? How much do they transfer to females? I will investigate how various important factors influence ejaculates in ageing males, such as nutrition, health and mating activity. I will also test whether interventions that increase lifespan, such as dietary restriction (a reduction in food intake without starvation), or the manipulation of genes involved in nutrient-sensing pathways, can lead to healthier ejaculates in ageing males. Combining the information gleaned from these experiments with evolutionary theory I will make predictions about how male ejaculate ageing should affect female fertility and reproductive success, and the outcome of sperm competition between males. In the second part of the project I will test evolutionary theories, to tell us how male ageing affects the adaptive reproductive decisions of males and females. For example, are females better off mating with young or old males? Does the sperm-competitive ability of males change as they age? By genetically manipulating male reproductive proteins I will be able to uncover the genes that causes such age-related changes. The goal of the project is to reveal the importance of age-related changes in the ejaculate, whether anything can be done to ameliorate negative effects of ejaculate ageing, and to help explain the age-mediated reproductive decisions that males and female make.