Life before death: Epigenetics of ageing
Changes in how DNA is translated by means other than modifications in the basic code come under the umbrella of epigenetics. The EU-funded IDEAL (Integrated research on developmental determinants of aging and longevity) project has examined the role of epigenetics in growing old, even before birth in the womb. They also looked at the genetic control of the ageing process. IDEAL showed how nutrition, infection, hormonal treatments and assisted reproductive technology (such as in vitro fertilisation) affect DNA, chronic disease and longevity. For example, incorrect thyroid signalling in bone formation in humans during development affected genetic and epigenetic variation related to late risk of osteoarthritis. However, it's not all bad news as early life environment effects can be counteracted. Many of the physiological and genomic consequences of a high fat diet during development in mice, for example, could be reversed in middle age by lower fat diet. For humans, lifestyle interventions changed metabolic health. This plasticity in physiological systems was observed across a range of species. IDEAL created reference datasets of genes and methylated loci sensitive to early exposures such as infection and stress hormones. The team developed a metro map like structure to illustrate the effects of human genetics, transcriptomics, methylomics and translational 'omics. Data cites references to the appropriate study, effects of gender and phenotypes for example and the end-result, effects on ageing. IDEAL also built a software tool that looks at protein interactions in the cell and how they change as an organism ages. IDEAL research has revealed multiple longevity loci. Birth weight for example, links early and late life features with healthy ageing. Age-changes in biomarkers were found in multiple genomes and biomes including the nuclear and mitochondrial genomes and the gut biome. The IDEAL list of potential biomarkers could serve as a basis for research into classification tools for absolute morbidity and mortality risk. The IDEAL project has obtained promising results for type 2 diabetes, premature ovarian insufficiency and menopause. Further research could investigate which pharmaceutical or nutritional interventions change or reverse epigenetic effects.
Keywords
Epigenetics, ageing, IDEAL, plasticity, interventions
