Senescence-accelerated OXYS rats: A genetic model of premature aging and age-related diseases

Abstract

A genetic model of accelerated senescence and the associated diseases in the OXYS strain of rats was established by selection and inbreeding of Wistar rats sensitive to the cataractogenic effects of galactose. In the first five generations, the development of a cataract was induced by galactose overconsumption, and, subsequently, the selection was carried out for early spontaneous cataract, genetically linked with the latter animals that inherited a set of features of premature aging. At present, there is already the 103rd generation of OXYS rats that develop retinopathy at young age, similar to age-related macular degeneration in humans, osteoporosis, arterial hypertension, accelerated thymus involution, sarcopenia, and neurodegenerative changes in the brain with the features characteristic for Alzheimer’s disease, in addition to cataracts. This review discusses possible mechanisms of their accelerated senescence: the results of comparison of retinal transcriptomes between OXYS and Wistar (control group) rats at different ages, studies of the markers of Alzheimer’s disease in the retina and in certain brain regions, and the results of development of congenic strains of animals through a transfer of loci of chromosome 1 from OXYS to WAG rats that are associated with the signs of accelerated senescence. The uniqueness of OXYS rats lies in the complex composition of manifestations of the traits; accordingly, this rat model can be used not only for studies of the mechanisms of aging and pathogenesis of age-related diseases but also for objective evaluation of new methods of treatment and prevention.