Healthy ageing determined from before birth
The EU-funded multidisciplinary project EURHEALTHAGEING (European research on developmental, birth and genetic determinants of ageing) has integrated genetic, epigenetic, biochemical, bioinformatic and statistical approaches to unravel the molecular basis of ageing. The researchers used data from studies including TwinsUK and the Hertfordshire Cohort Study. A genome-wide association study (GWAS) and next-generation sequencing were applied to birth weight in the two study cohorts. Metabolomic screens identified the top 25 metabolites in low birth weight babies and the gene neuroblastoma breakpoint family 1 was implicated in a number of developmental and neurogenetic disorders. To analyse genotyping from the twin studies, a workflow-based cloud enabled analysis platform was developed. For scalability, flexibility and reusability, default inputs are used for user-friendly handling. Scientists are also working on data integration to build a comprehensive user-friendly database. The epigenetic study identified 96 methylation probes and the genome-wide methylation arrays were analysed. Study of specific post-translational modifications identified three main markers. Analysis with age-related traits showed an association of Citrullinated vimentin with cardiovascular disease risk, of Type I collagen and Type III collagen with osteoarthritis and gout. Significant pathways from the genetic and epigenetic analysis are involved in blood pressure, obesity and height and are in agreement with published findings linking early growth factors with disease in adulthood. A genetic risk score correlates with metabolic disease and blood pressure in adults. From both genetic and epigenetic data, the MIA3 gene is associated with cardiovascular disease. The EURHEALTHAGEING consortium has disseminated project activities through lectures, presentations and a summer school. Seventeen peer-reviewed scientific publications were published. Successful activities would realise the development of tests and products that promote healthy ageing and an independent active lifestyle.
Keywords
Healthy ageing, longevity, biomarker, genetic, epigenetic
