The Harwell Aging Screen
Diseases associated with ageing pose an increasing social and financial burden on society and represent a vital imperative for research in the biomedical sciences. Despite the complications of genetic background in human populations and the confounds of environment there has been considerable advances, particularly through Genome-wide association studies (GWAS) in identifying loci involved in diseases of aging. Nevertheless, this is only a first step towards a more fundamental understanding of the genetic pathways involved. Animal models are required both to test our understanding of these pathways, as well as to provide the tools for developing and assessing therapeutics.
We are undertaking the first large-scale project to employ mutagenesis and phenotyping programmes to specifically generate new recessive models of late onset or age-related disease. The emphasis will be on the exploration of phenotype space in aging mouse mutant populations providing us with the opportunity to: identify genes and pathways involved in age related disease, scrutinise these models for biomarkers of age related disease, and provide better platforms for pre-clinical assessment of new therapies for such diseases.
Pedigrees will be aged up to 18 months and undergo phenotyping across a wide range of disease areas. Analysis will occur at several defined time points throughout the life of the mice and the phenotypes included in the screening include diabetes and metabolism, neurobehaviour, cognitive tests, bone analysis, renal function, cardiac disease, liver function, sensorineural (vision and hearing), and a comprehensive clinical chemistry screening. Other screens are also in development. Detailed histological analysis will be carried out as part of the terminal analysis and a biobank of samples taken at different ages will also be established for retrospective analysis. The age challenged mice will be an important resource for many research groups, identifying novel genes and pathways resulting in age-related phenotypes along with the potential to discover new biomarkers.