How are life history and reproductive behaviour coordinated?

我们为什么会变老？人类和大多数动物一样，随着年龄的增长，保持健康身体、生育后代和抵抗疾病的能力都会下降。这是一个令人困惑的现象。一种能够永远进行交配和繁殖的动物将处于进化优势，因为它将最大限度地提高基因对下一代的贡献。然而，绝大多数动物都做不到这一点。自然界告诉我们，在其他条件相同的情况下，长寿和繁殖之间通常存在负相关关系：动物往往要么是快速繁殖者，要么是长寿者。这被认为是因为资源是有限的，动物可以将可用的资源投入到维持身体的长寿中，也可以将其投入到大量的交配和后代生产中-但不能两者兼而有之。或者，交配和生育后代的努力可能会对身体造成不可逆转的损害，最终导致其衰退。无论如何，进化论预测永生和高生育率是不可能的，因此最近关于基因操纵的报道引起了人们的极大兴趣，这些基因操纵可以延长寿命而不减少生育。这项在线虫和果蝇等无脊椎生物中进行的研究表明，不同的过程可能控制寿命和繁殖。如果这是真的，那么进化论将面临一个重大挑战。然而，长寿，高繁殖力的蠕虫和苍蝇是在实验室中进行基因改造和实验的，这种环境缺乏自然界的压力和压力。此外，实验通常是在特定的性条件下进行的：要么很少或没有交配的机会，要么交配是无限制的。这使问题变得复杂，因为性活动本身对寿命有很大的影响：大量的交配导致这些物种的过早死亡。我最近的工作表明，一些基因改造，增加寿命的女性果蝇，也使他们不愿意与男性交配。因此，如果研究人员在实验中不控制或测量动物的性活动，他们可能会错误地将寿命延长归因于基因操作的直接影响，而不是由于性活动减少而延长寿命。此外，我们不知道性活动的差异如何影响长寿苍蝇的寿命，或者性别特异性行为是否会影响寿命。我的项目的目的是研究果蝇（Drosophila melanogaster）的寿命和生殖行为之间的关系，以解决上述问题。首先，这项工作将确定男性和女性的寿命调节和性行为调节之间的遗传联系，以了解寿命的遗传调节如何影响苍蝇年龄的性活动，从而确定苍蝇是否有可能性活跃更长时间。其次，我将测试男性和女性经历的交配机会的数量是否会影响寿命的遗传控制（即长寿突变体对不同水平的生殖活动的“鲁棒性”）。最后，我将测试性别特异性行为是否会影响寿命，并解释两性之间寿命的差异。这些实验的结果将让我们清楚地了解性与寿命之间的关系：操纵寿命如何影响性行为，以及改变性行为如何影响寿命。这将有助于我们理解动物如何最大限度地延长生殖寿命，以及为什么性行为似乎与衰老有着不可避免的联系。

Why do we age? In humans, as in most animals, the ability to maintain a healthy body, produce offspring and fight disease declines as we get older. This is a puzzling phenomenon. An animal that could carry on mating and reproducing forever would be at an evolutionary advantage because it would maximise its contribution of genes to the next generation. However, the vast majority of animals can't do this. The natural world shows us that, all else being equal, there is usually a negative relationship between longevity and reproduction: animals tend to be either fast reproducers or long-lived. This is thought to be because resources are limited, and animals can either invest the available resources in maintaining their body for a long life or they can invest them in lots of mating and offspring production - but not both. Alternatively, the efforts of mating and producing offspring might cause irreversible damage to the body that ultimately leads to its decline. Either way, evolutionary theories predict that eternal life and high rates of fecundity should be impossible.Recent reports of genetic manipulations that increase lifespan without reducing reproduction have therefore generated much interest. The research, conducted in invertebrate organisms such as the nematode worm and the fruit fly, suggests that different processes might control lifespan and reproduction. If this were true, then evolutionary theory would face a major challenge. However, the long-lived, high fecundity worms and flies were genetically modified and experimented upon in the laboratory, an environment that lacks the stresses and pressures of the natural world. Furthermore, experiments are often carried out under specific sexual conditions: either where there is little or no opportunity to mate, or where mating is unlimited. This complicates matters because sexual activity per se has a large effect on lifespan: lots of mating results in early death in these species. My recent work has shown that some genetic modifications that increase the lifespan of female fruit flies, also makes them less willing to mate with males. Thus, if researchers do not control or measure the sexual activity of animals in their experiments, they could mistakenly attribute increased lifespan to the direct effect of genetic manipulations rather than long-life as a result of less sexual activity. Moreover, we don't know how differences in sexual activity affects lifespan in long-lived flies, or whether sex-specific behaviour impacts lifespan. The aim of my project is to investigate this relationship between lifespan and reproductive behaviour in the fruit fly, Drosophila melanogaster, to address the problems posed above. Firstly, the work will identify the genetic links between the regulation of lifespan and the regulation of sexual behaviour in males and females, to find out how the genetic regulation of lifespan affects sexual activity as flies age, and thus whether it is possible for flies to be sexually active for longer. Secondly I will test whether the number of mating opportunities that males and females experience affects the genetic control of lifespan (i.e. how 'robust' long-lived mutants are to different levels of reproductive activity). Finally I will test whether sex-specific behaviours affect lifespan and can explain differences in longevity between the sexes. The results of these experiments will give us a clear picture of the relationship between sex and lifespan: how manipulating lifespan affects sexual behaviour and how changing sexual behaviour affects lifespan. This will help us understand how animals maximise their reproductive lifespan and why sex seems to have an inevitable association with senescence.