Improving human health has been enormously helped by deciphering the human genome. Yet if we are to better understand physical processes, for example the onset of disease or the impact of ageing, we need to know more about how genes are actually organised and expressed, as well as their sequence. Problems with this control mechanism, referred to as our ‘epigenome’ have been implicated in common diseases such as diabetes and cancer. Our epigenome has also been linked to health declines related to ageing. With the ageing population ever-growing around the world, this is a challenge of increasing importance.
Yet there is strong evidence that epigenomic changes can be reversed. Investigating how this might be possible requires the production of reference maps for all relevant human cell types, accurate modelling, allied with efforts to track how epigenetic profiles, at both the individual and population level, are influenced by environmental factors.
Dietary restriction can protect and reprogramme
A recent study published in the Genome Biology journal focusses on work undertaken to understand one such environmental factor, namely that of diet. During ageing, it is known that reducing food intake can increase health and extend lifespan in a number of species, including rodents and rhesus monkeys. Indications are that Dietary Restriction (DR) can also improve metabolic and cardiovascular health in humans. But exactly how this happens is not yet well understood.
The study, drawing on the work of the EU-funded project ERA (and supported by that of BLUEPRINT and EPIGENESYS – also EU-funded), found that mice lifespans could be increased by 30 % when diets were reduced to 40 % of their control group. To find an explanation, the researchers tracked the epigenetic impact of DR across the whole genome. They discovered that age-related changes to DNA methylation (a mechanism used by cells to control gene expression) across the genome, were substantially prevented by DR. Additionally, DR also influenced the reprogramming of lipid metabolism genes resulting in protection against age-related increases of fat deposits in the liver and the development of hepatic insulin resistance, symptomatic of type 2 diabetes.
Professor Wolf Reik, Head of the Epigenetics programme at the Babraham Institute, (part of the EPIGENESYS project consortium) is quoted as saying, ‘This work significantly advances our understanding of epigenetic regulation of ageing and dietary restriction by connecting the epigenome more directly with lipid changes associated with healthy ageing. Future work may reveal if dietary restriction leaves a long term epigenetic memory in the genome.’
Looking to the future, the paper points out that recent research is adding to the stock of mounting evidence for ‘particular components of nutrient-sensing pathways’ that could prove valuable as pharmaceutical targets for drugs designed to prevent age-related disease.
A future where chemistry can mimic the effects of dietary restriction to reduce age-related illness will require a greater understanding of the role that epigenomes play and more knowledge about the underlying biological processes. The International Human Epigenome Consortium (IHEC) was established to coordinate efforts to achieve just these aims.
The recently completed EU-funded project BLUEPRINT contributed to these efforts as it was set up to generate around 100 reference epigenomes to study (focusing on blood cell disease) and to create new targets for compounds and the development of smart technologies for better diagnostic tests. Likewise, EPIGENESYS contributed by providing a quantitative representation of epigenetic mechanisms to better enable predictive modelling.