Mechanisms of Sensory Modulation of Aging in Drosophila

描述（由申请人提供）：科学家和外行长期以来一直对感官着迷。亚里士多德区分了其中的四种，每一种都与四种元素中的一种联系在一起-视觉与水，声音与空气，嗅觉与火，触摸与土地。从那时起，我们已经意识到了更多的东西，包括那些涉及位置或疼痛的东西。现在，一系列学科的研究表明，感官知觉能够调节生理和健康的许多方面。事实上，从线虫（秀丽隐杆线虫）和果蝇（黑腹果蝇）的研究中得到的证据已经证实，衰老受到感觉系统的强烈调节，而且这种调节在进化上是保守的。Apfeld和Kenyon使用线虫模型来证明抑制感觉输入可以延长寿命。我们实验室和其他人的后续工作将这些结果扩展到果蝇，并揭示了感官知觉和衰老之间日益微妙的关系。例如，一些感觉神经元可以延长寿命，而另一些则会抑制寿命。在这次更新中，我们将在母奖的基础上继续剖析大脑中感官知觉和感官体验的解释调节健康和寿命的分子机制。在建立了调节衰老的特定嗅觉和味觉操作之后，我们将开始确定这些感觉方式通过重叠或不同的机制来调节衰老的程度。然后，我们将基于我们对影响寿命的特定神经肽和神经信号分子的了解，来询问果蝇大脑中功能相关的神经元组，并确定那些能够调节寿命的神经元组。我们实验室和其他实验室的最新发现揭示了感知神经生物学与复杂行为输出之间的因果关系;因此，果蝇可以说是最相关，最强大，最灵活的模型系统，以剖析衰老和整个生物体生理学的中枢控制机制。我们相信，利用简单模型系统的神经生物学来研究感觉系统的生物学影响，将有助于深入了解感官知觉对整个分类群的广泛影响。为了支持这一观点，有证据表明，人类的感官知觉可以调节健康和衰老，以我们尚不了解的方式对社会和营养线索作出反应。因此，除了提供发现衰老基本机制的机会外，我们的工作还可能为人类带来创造性的干预策略。

DESCRIPTION (provided by applicant): Scientists and laypeople have long been fascinated by the senses. Aristotle distinguished four of them, each linked with one of the four elements - vision with water, sound with air, smell with fire, and touch with earth. Since that time we have become aware of many more, including those involving position or pain. Now, research across a range of disciplines has revealed that sensory perception is capable of modulating many aspects of physiology and health. Indeed, evidence from work in the nematode, Caenorhabditis elegans, and from our work in the fruit fly, Drosophila melanogaster, has established that aging is strongly modulated by sensory systems and that this modulation is evolutionarily conserved. Apfeld and Kenyon used the nematode model to show that suppression of sensory input could extend lifespan. Subsequent work from our lab and others has extended these results to Drosophila and revealed an increasingly nuanced relationship between sensory perception and aging. For example, some sensory neurons enhance longevity while others suppress it. In this renewal, we build upon the results from the parent award to continue our dissection of the molecular mechanisms by which sensory perception and the interpretation of sensory experiences in the brain modulate health and lifespan. Having established specific olfactory and gustatory manipulations that modulate aging, we will begin by determining the extent to which these sensory modalities act through overlapping or distinct mechanisms to modulate aging. We will then build on our knowledge of specific neuropeptides and neuro- signaling molecules that influence longevity to interrogate functionally relevant groups of neurons in the fly brain and identify those capable of modulating lifespan. Recent discoveries from our laboratory and others have revealed cause and effect relationships linking the neurobiology of perception to complex behavioral outputs; thus making Drosophila arguably the most relevant, powerful, and flexible model system to dissect the mechanisms underlying central control of aging and whole-organism physiology. We believe that harnessing the neurobiology of simple model systems to study the biological impact of sensory systems will yield insights into the broad influence of sensory perception across taxa. In support of this view, there is evidence to suggest that human sensory perception can modulate health and aging in response to social and nutritional cues in ways that we do not yet understand. In addition to providing an opportunity to discover basic mechanisms of aging, therefore, our work may also lead to creative intervention strategies for humans.