Homeostatic maintenance of the auditory system and its relation to age-dependent hearing loss: A Drosophila model organ study

在英国，70岁以上的人中有70%患有听力下降。然而，我们默许了这种与年龄有关的感官衰退，就像我们认为它们在我们生命的大部分时间里都是理所当然的一样。从科学的角度来看，这两种现象同样值得注意。我们的眼睛和耳朵是生活世界的一部分，因此它们不断需要代谢能量，并永久暴露在无数的环境挑战中。与花岗岩相反，生物系统在几天、几个月甚至几年的时间内保持不变的特性，需要一个解释。如果在某个时候，没有任何明显的外部原因，系统性能最终下降，则需要第二种解释。本研究项目将研究这两种现象，并测试它们在机械上相互关联的假设。换句话说，维持我们听觉的细胞机制是什么，这些机制是如何随着时间的推移而恶化的？使用果蝇的触角耳朵作为模型感觉器官，我们将（i）解剖在果蝇的整个生命过程中保持敏感听觉的分子网络，（ii）研究这种维持或稳态在衰老过程中的变化。我们将专门检验这样一个假设，即指导生长中苍蝇耳朵构造的分子网络（我们对此已经了解很多）也有助于其在成年期的稳态控制（我们对此知之甚少）。重要的是，已知耳朵结构的分子网络在苍蝇和人类之间有很多共同之处，我们希望我们的研究将提供一个相关的模型来理解人类听力的下降。

In the UK, some 70% of people over 70 suffer from decline of hearing. Yet, we have acquiesced into this age-related decay of our senses almost as tacitly as we take their faultless operation for granted for most of our lives. Scientifically, both of these phenomena are equally remarkable. Our eyes and ears are parts of the living world and as such they are in constant need of metabolic energy and permanently exposed to countless environmental challenges. In contrast to a granite rock, a biological system that retains constant properties over periods of days, months, or even years, needs an explanation. If then at some point, and without any obvious external cause, system performance eventually declines, a second explanation is required. This research project will study both of these phenomena and test the hypothesis that they are mechanistically interlinked. In other words, what are the cellular mechanisms that maintain our sense of hearing and how do these mechanisms deteriorate over time? Using the antennal ears of the fruit fly Drosophila melanogaster as a model sensory organ, we will (i) dissect the molecular network that maintains sensitive hearing throughout the fly's life course and (ii) study how this maintenance, or homeostasis, changes during ageing. We will specifically test the hypothesis that the same molecular networks that direct the construction of the ear in the growing fly (about which we already know quite a lot) also contribute to its homeostatic control during adult life (about which we know very little). Importantly, the molecular networks of ear construction are known to have much in common between flies and humans, and we expect our research will provide a relevant model to understand decline of hearing in humans.