Mechanisms of olfactory modulation of aging in Drosophila

古老的信号通路检测、解码和利用环境刺激来协调新陈代谢、生长、 和成熟。长期以来，环境线索引发生命史模式改变的力量一直受到人们的关注。 这一点得到了野外生物学家的认可，这种可塑性的好处是显而易见的。可变环境条件 要求个人使用外部信息来做出计算决定，例如是否等待 或者致力于繁殖，以最大限度地提高繁殖适应性。事实上， 线虫，秀丽隐杆线虫，以及我们在果蝇，黑腹果蝇中的研究， 表明衰老的感觉控制在进化上是保守的。消融特定的感觉神经元， 蠕虫影响寿命，感觉信号传导所需的基因突变也是如此。工作的开展 实验室已经表明，暴露于食物中的气味会缩短寿命，并部分挽救生命。 饮食限制的好处此外，一个单一的气味受体的突变， 嗅觉缺失，导致惊人的寿命：中位寿命增加60%（近30天）， 野生动物虽然突变果蝇有正常的大小和代谢率，但它们对饥饿有抵抗力。 和高氧，并且它们表现出增加的甘油三酯储存。我们试图阐明（i）特定的嗅觉 调节寿命的刺激;（ii）哪些细胞，分子和途径与相关的感觉 信息;以及（iii）这些信息如何指导改变寿命的后续结果。我们将确定 嗅觉突变果蝇的寿命延长是否依赖于已知的长寿途径， 通路;嗅觉信号是否在成年阶段急性作用;以及特定的气味受体是否 调节果蝇的寿命。我们的研究将为后续分析提供分子证据。 调节果蝇衰老的特定分子和生物过程。这些研究也可能 阐明哺乳动物中控制发育、代谢和衰老的感觉信号网络。

Ancient signaling pathways detect, decode, and use environmental stimuli to coordinate metabolism, growth, and maturation. The power of environmental cues to trigger alterations in life history patterns has long been recognized by field biologists, and the benefit of such plasticity is clear. Variable environmental conditions demand that individuals use external information to make calculated decisions, such as whether to wait out the bad times or commit to reproduction, to maximize reproductive fitness. Indeed, evidence from work in the nematode worm, Caenorhabditis elegans, and from our work in the fruit fly, Drosophila melanogaster, has shown that sensory control of aging is evolutionarily conserved. Ablation of specific sensory neurons in the worm affects lifespan, as do mutations in genes required for sensory signal transduction. Work in our laboratory has shown that exposure to food-based odorants reduces lifespan and partially rescues the benefits of dietary restriction. Moreover, mutation of a single odorant receptor, which leaves flies broadly anosmic, results in striking longevity: up to 60% (nearly 30 days) increase in median lifespan compared to wild-type animals. While mutant flies have normal size and metabolic rate, they are resistant to starvation and hyperoxia, and they exhibit increased triglyceride storage. We seek to elucidate (i) specific olfactory stimuli that regulate longevity; (ii) which cells, molecules, and pathways transduce relevant sensory information; and (iii) how this information directs subsequent outcomes that alter lifespan. We will determine whether the increased lifespan of olfactory mutant flies relies on known longevity pathways or involves novel pathways; whether olfactory signaling acts acutely in the adult stage; and whether specific odorant receptors regulate longevity in Drosophila. Our studies will provide molecular evidence for subsequent analysis of specific molecules and biological processes that regulate aging in Drosophila. These studies may also illuminate sensory signaling networks in mammals that control development, metabolism, and aging.