Mechanisms of Sensory Modulation of Aging in Drosophila

果蝇衰老的感觉调节机制

• 批准号: 8635966
• 负责人: SCOTT PLETCHER
• 金额: $ 31.39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635966
• 关键词: Affect; Afferent Neurons; Aging; Air; Allatostatin; Award; Behavioral; Biological; Biological Models; Brain; Brain region; Caenorhabditis elegans; Complex; Cues; Data; Discipline; Dissection; Drosophila genus; Drosophila melanogaster; Elements; Fire - disasters; Food; Funding; Genetic; Genetic Epistasis; Health; Human; Influentials; Intervention; Knowledge; Laboratories; Lead; Libraries; Link; Longevity; Mammals; Maps; Measures; Mediating; Modality; Modeling; Molecular; Mutation; Nematoda; Neurobiology; Neurons; Neuropeptides; Nutritional; Output; Pain; Parents; Partner in relationship; Pathway interactions; Pattern; Perception; Phenotype; Pheromone; Physiology; Population; Positioning Attribute; Process; Production; Research; Research Support; Scientist; Sensory; Signal Transduction; Signaling Molecule; Sleep; Smell Perception; Social Environment; System; Taste Perception; Taxon; Time; Touch sensation; Vision; Water; Whole Organism; Work; adipokinetic hormone; base; dietary restriction; experience; fascinate; flexibility; fly; functional group; genetic analysis; genetic manipulation; healthy aging; insight; insulin signaling; mind control; mutant; neuropeptide F; neuroregulation; novel; public health relevance; receptor; research study; response; sensory mechanism; sensory system; social; sound; tool; ward

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.

描述（由申请人提供）：长期以来，科学家和外行人一直对感官着迷。亚里士多德（Aristotle）区分了其中的四个，每个都与四个元素之一联系在一起 - 视觉，水，空气，闻起来有火，并与地球接触。从那时起，我们就已经意识到了更多，包括涉及位置或痛苦的人。现在，跨各种学科的研究表明，感官感知能够调节生理和健康的许多方面。实际上，秀丽隐杆线虫和我们在果蝇中的工作（果蝇Melanogaster）的工作中的工作证明，衰老是由感觉系统强烈调节的，并且这种调制在进化上是保守的。 Apfeld和Kenyon使用线虫模型表明感觉输入的抑制可以延长寿命。我们实验室和其他人的随后工作将这些结果扩展到了果蝇，并揭示了感觉知觉和衰老之间越来越细微的关系。例如，一些感觉神经元可以增强寿命，而另一些则可以抑制它。在这种续约中，我们基于父母奖的结果，以继续对分子机制进行解剖，通过这种机制，感官感知和对大脑健康和寿命中感觉体验的解释的解释。在建立了调节衰老的特定嗅觉和味觉操纵之后，我们将首先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，我们将基于对特定的神经肽和神经信号分子的了解，这些神经肽和神经信号分子会影响寿命，以询问蝇脑中与功能相关的神经元的群体，并确定能够调节寿命的人。我们实验室和其他人的最新发现揭示了将感知神经生物学与复杂行为产出联系起来的因果关系。因此，可以说是果蝇是最相关，最有力和灵活的模型系统，以剖析衰老和全生物生理学中心控制的机制。我们认为，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产生对整个分类单元感官感知的广泛影响的见解。为了支持这种观点，有证据表明，人类感觉感知可以以我们尚不了解的方式来调节社会和营养线索的健康和衰老。因此，除了提供机会发现衰老的基本机制外，我们的工作还可能导致对人类的创造性干预策略。