An investigation of the impact of diet and lifestyle on the epigenome in the ageing intestinal epitheli

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Epigenetics refers to heritable changes in gene function that are not dependent on DNA sequence variation and includes the covalent modification of the DNA by methylation or the histone proteins in chromatin by methylation, acetylation, phosphorylation or ubiquitinylation, which can alter its conformation and hence its accessibility to the transcription machinery. It is now widely acknowledged that aberrant epigenetic modifications are associated with and contribute to the development of several chronic diseases including those of the gastrointestinal tract. Epigenetic factors provide a heritable, reversible and dynamic mechanism for regulating gene expression in response to the external stimuli induced by lifestyle/environment. As interpreters of environmental cues and integrators of multiple signaling pathways, epigenetic changes re-programme gene expression by modifying chromatin in a precise, gene- or cell-specific fashion and so determine transcriptional, phenotypic and functional outcomes. Ageing has also been shown to have a profound effect on DNA methylation in many cell types in various organisms and striking evidence exists for the environment or lifestyle as the major contributor to these age-related effects on the epigenome. This strongly suggests that environmental factors act on individuals throughout life, modifying gene expression through epigenetic mechanisms that have important implications for health. In a cross-sectional study involving healthy human volunteers over a broad age-range we are evaluating the influence of specific nutritional, metabolic and anthropometric factors on age-related DNA methylation in the colonic epithelium. Outcomes from this study are informing studies using a combination of in vivo and in vitro approaches in mice and cultured cells to explore the mechanisms by which specific dietary constituents and metabolic factors impact upon DNA methylation.

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