Supporting healthy ageing through the microbiota: A Drosophila model

通过微生物群支持健康衰老：果蝇模型

• 批准号: 2118991
• 金额: --
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2118991
• 关键词: Supporting; healthy; ageing; through; microbiota

Changes in the intestinal microbiota (dysbiosis) have been implicated in age-related decline, being correlated with measures of frailty in the elderly. However, the accessibility of this microbial population to simple interventions, such as diet or probiotics, has also highlighted its potential as a partner in the maintenance of life-long health. The rational design of interventions targeting the microbiota will require a greater understanding of the mechanistic basis of microbial influence on host health throughout the life course. The fruit fly, Drosophila melanogaster, is one of the premier model organisms for ageing research and carries a simple intestinal microbiota containing a number of taxa found in the human intestine. We have shown that shifts in the aging Drosophila microbiota broadly echo those seen in ageing people, and are also strongly implicated in age-related decline (Clark et al 2015). This project will capitalize on these similarities, and the strengths of the Drosophila model, in order to characterise the molecular mechanisms that drive the impact of dysbiosis on host healthThe first stage of this project will utilise detailed time-course studies of multiple markers of age-related decline. Our focus will be the characterisation of microbial influence on decline and will encompass the intestine and multiple distal tissues. In addition to the assays of age-related decline that we use in the Clark lab, the student will take a rotation in the Sanz lab (Newcastle) in order to measure the impact of microbial exposure and ageing on mitochondrial function in a number of tissues.Following this, we will use metabolomic and transcriptomic approaches to measure change in metabolism and gene expression of the intestinal microbiota during host aging. These data will provide us with a number of candidate metabolic pathways or single genes that are modified with age and may drive the influence of the microbiota on host health. These data will therefore form the basis of the final stage of this project in which we will use the powerful genetic tools available in Drosophila in combination with bacterial genetics to test the impact of our candidates on age-related decline in the host. The techniques and tools used will be determined by the nature of the gene/pathway of interest, but will focus on identifying potential targets for interventions to prevent or delay decline across multiple tissues.

肠道微生物群的变化（菌群失调）与年龄相关的衰退有关，与老年人的虚弱程度相关。然而，这种微生物群体易于接受饮食或益生菌等简单干预措施，也凸显了其作为维持终生健康的伙伴的潜力。针对微生物群的干预措施的合理设计将需要更好地了解微生物在整个生命过程中对宿主健康影响的机制基础。果蝇（Drosophila melanogaster）是衰老研究的主要模型生物之一，携带简单的肠道微生物群，其中含有人类肠道中发现的许多分类单元。我们已经表明，衰老果蝇微生物群的变化与老年人中观察到的变化大体相似，并且也与年龄相关的衰退密切相关（Clark et al 2015）。该项目将利用这些相似性以及果蝇模型的优势，以描述驱动生态失调对宿主健康影响的分子机制。该项目的第一阶段将利用对与年龄相关的衰退的多种标记物进行详细的时间过程研究。我们的重点是表征微生物对衰退的影响，并将涵盖肠道和多个远端组织。除了我们在克拉克实验室使用的与年龄相关的衰退分析之外，学生还将在桑兹实验室（纽卡斯尔）进行轮换，以测量微生物暴露和衰老对许多组织中线粒体功能的影响。接下来，我们将使用代谢组学和转录组学方法来测量宿主衰老过程中肠道微生物群代谢和基因表达的变化。这些数据将为我们提供许多候选代谢途径或单个基因，这些途径或基因会随着年龄的增长而改变，并可能推动微生物群对宿主健康的影响。因此，这些数据将构成该项目最后阶段的基础，在该项目中，我们将使用果蝇中可用的强大遗传工具与细菌遗传学相结合，以测试我们的候选者对宿主与年龄相关的衰退的影响。所使用的技术和工具将由感兴趣的基因/通路的性质决定，但将侧重于确定干预措施的潜在目标，以预防或延缓多个组织的衰退。