Linking genetic and epigenetic risk factors increased risk of frailty and cognitive decline

In order to investigate the origins of frailty and cognitive impairment and elucidate the differences, it is important to start with the genetic layout of the individuals - an underlying continuous risk throughout life - as well as understand the epigenetic modifications that alter the risk function over time. The Toledo Study of Health Ageing (TSHA) is ideally suited to study the environmental and individual level risk factors that modify the association between known genetic and epigenetic risk factors of frailty and cognitive impairment in Spain. The TSHA is a longitudinal follow-up study with triennial rounds of interview and physiological examination. Recently the participants of this study participated in a large scale European Initiative (FRAILOMICS) to investigate some of the most preeminent -OMIC risk factors of frailty. The data collected during this initiative will be enriched by adding genome-wide genotype and gene-expression data. In addition, the TSHA is constantly renewed allowing the evaluation of important modifiers such a birth cohort that act as powerful modifiers of the genetic risk.

It has been proposed that epigenetic modifications are responsible for the differential expression of the ageing phenotype as frail or cognitively impaired independent of genetic risk. The Instituto de Salud Carlos III is to fund a project that links to FRAILOMIC in that in FRAILOMIC we selected only candidate genetic markers, the grant will finance to measure 'al'" genetic markers and relate them to frailty to. In addition, the researchers aim to perform DNA Methylation analysis.

The objectives of the 2-year study are to seek to identify new genetic risk factors associated to phenotypes of aging such as gait speed, hand grip strength, investigate if known genetic risk factors of dementia are also associated to frailty, to investigate if epigenetic modifications are responsible for the increase in frailty and cognitive decline among the elderly with type 2 diabetes and see if epigenetic modifications of known genetic risk factors for dementia differentially affect the development of frailty vs. cognitive decline.