Frailty denotes a multidimensional syndrome that gives rise to vulnerability to stressors and leads to an increase of the age-related decline of different physiological systems and cognitive abilities. Frailty is associated with an increased risk of disability, dependency, hospitalization and death. However, our understanding of the biological mechanisms through which frailty arises is limited, and the environmental, lifestyle and genetic risk factors for frailty are not well characterized. Since it has been demonstrated that frailty is potentially preventable, and can be even reverted in its primary stages, having a deep knowledge on the events and features involved in frailty development in the older age is critical.
In spite of the number of cellular alterations known to be related to frailty in older adults, studies on this topic are still scarce and limited to some cell targets (genomic instability, oxidative stress, and DNA damage or repair). Moreover, genetic association studies on the origin of frailty have not rendered consistent results so far.
This proposal seeks access to UK Biobank data to support efforts to identify environmental and lifestyle factors, and also genetic variants, contributing to frailty development in older adults. The large sample size offers an unparallel opportunity to study the range of population of older adults (aged 60 years and over).
We will conduct epidemiological analyses to identify demographic, clinical, environmental and lifestyle factors associated with the risk of frailty in older adults. We will also perform genome-wide association analyses of DNA-genotyping data to identify genetic variants that increase the likelihood of frailty development. We request access to data generated for all participants in UK Biobank aged 60 years and over. We request information on relevant demographic, clinical, environmental and lifestyle factors that can be potentially associated with frailty. We also request genetic data (from direct genotyping and imputation) to evaluate association of genetic variants with frailty.
The results obtained will increase the knowledge on factors associated with frailty status and be useful to obtain insights into frailty physiopathology. These data could be used to identify individuals at higher risk, allowing to anticipate adverse physical and psychological health effects related to frailty, to implement effective interventions (pharmacological and non-pharmacological) directed to prevent the decline in physical capacity, cognitive status and disability, organize the healthcare assistance, and, ultimately, to reduce the economic and social impact of population ageing.
