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

在英国，70岁以上的人中约有70%患有听力下降。然而，我们默许了这种与年龄相关的感官衰退，就像我们在生活的大部分时间里认为它们的完美运作是理所当然的一样。从科学上讲，这两种现象都同样值得注意。我们的眼睛和耳朵是生活世界的一部分，因此它们经常需要新陈代谢能量，并永久地暴露在无数的环境挑战中。与花岗岩岩石不同，生物系统在几天、几个月甚至几年的时间里保持不变的性质，需要一个解释。如果在没有任何明显外部原因的情况下，在某一时刻，系统性能最终下降，则需要另一种解释。这项研究项目将研究这两种现象，并检验它们在机械上相互关联的假设。换句话说，维持我们听力的细胞机制是什么？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式感官器官，我们将(I)解剖在果蝇整个生命过程中维持灵敏听力的分子网络，(Ii)研究这种维持或内稳态在衰老过程中的变化。我们将专门测试这一假设，即指导成长苍蝇耳朵构造的相同分子网络(我们已经知道相当多)也有助于成年苍蝇(我们对此知之甚少)的体内平衡控制。重要的是，众所周知，苍蝇和人类之间的耳朵结构的分子网络有很多共同之处，我们希望我们的研究将提供一个相关的模型来理解人类的听力下降。

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.