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

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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.