Epigenome-Microbiome crosstalk: A new way to maintain cognition at old age

表观基因组-微生物组串扰：维持老年认知的新方法

• 批准号: 418087534
• 负责人: Dr. Christiane Frahm
• 金额: --
• 依托单位: Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/418087534?language=en
• 关键词: Epigenome; Microbiome; crosstalk; new; way

Cognitive decline and dementia are among the most important aging-related health problems worldwide. Changes in lifestyle such as social interaction and physical activity – even if it starts late in life – are beneficial for maintaining cognition and healthy aging. The role of the gut microbiome in modulating brain function is currently of high interest. Gut microbiota sense and respond to environmental cues and as a result generate numerous metabolites important for host physiology. To elucidate the role of the gut microbiome in converting lifestyle changes into an improved cognition at old age we recently submitted a project (BA 2863/8-1, FR 1264/4-1 und KA 3541/6-1). Omics-technologies (sequencing of the transcriptome, the metagenome and the 16S rRNA) will be applied to analyse mice at different ages and following cognition-modulating interventions to build an in silico multi-scale model of microbiome-gut-brain communication. Very recent work, also from the applicants, has shown that aging is associated with pronounced changes in DNA-methylation and that the microbiome strongly influences this epigenetic mechanism. Thus, in this project we intend to complement our data set with information of the methylome (reduced representation bisulfite and whole methylome sequencing) in colon and brain samples. A subset of brain samples will be subjected to a cell-type-specific analysis. These epigenomic data will expand and complete our multi-scale metabolic model which will enable us to predict interactions between microbiome and brain in the course of aging, its relation to cognitive function and how they are influenced by interventions preserving cognition. Our model will serve in the future as essential basis for the rational design of microbiome-based therapies to counteract aging pathologies.

认知能力下降和痴呆症是全球最重要的与衰老有关的健康问题之一。生活方式的改变，如社会交往和体育活动-即使在生命的后期开始-对保持认知和健康老龄化有益。肠道微生物组在调节脑功能中的作用目前受到高度关注。肠道微生物群感知并响应环境信号，因此产生许多对宿主生理学重要的代谢物。为了阐明肠道微生物组在将生活方式改变转化为老年认知改善中的作用，我们最近提交了一个项目（BA 2863/8-1，FR 1264/4-1和KA 3541/6-1）。Omics-technologies（转录组，宏基因组和16 S rRNA的测序）将用于分析不同年龄的小鼠，并进行认知调节干预，以建立微生物组-肠道-大脑通信的计算机多尺度模型。同样来自申请人的最近的工作表明，衰老与DNA甲基化的显著变化相关，并且微生物组强烈影响这种表观遗传机制。因此，在这个项目中，我们打算用结肠和脑样品中的甲基化组（还原亚硫酸氢盐和全甲基化组测序）的信息来补充我们的数据集。将对脑样本的子集进行细胞类型特异性分析。这些表观基因组数据将扩展和完善我们的多尺度代谢模型，这将使我们能够预测微生物组和大脑在衰老过程中的相互作用，其与认知功能的关系以及它们如何受到保护认知的干预措施的影响。我们的模型将在未来作为合理设计基于微生物组的疗法以对抗衰老病理的重要基础。