Summary
In this supplement/revision application, we are focused on three important co-occurring clinical phenotypes in Down syndrome (DS): age-related immune system alterations, age-dependent hearing loss, and age-dependent cognitive decline (independently of Alzheimer’s disease). Our long-term objectives are to ask whether measuring biological and molecular markers of aging in chromosomally engineered mouse models of DS can help to answer (i) what are the genes on chromosome 21 that cause early aging epigenetic aging in DS? (ii) what are the genes on this chromosome that cause early biological aging in DS (iii) does epigenetic aging influence biological aging? and (iv) do early epigenetic and biological aging contribute to the above listed medical conditions? To lay a foundation for achieving these goals, in our 2-year aims, we seek to determine whether the duplications of two chromosome 21 orthologous chromosomal regions in our mouse models affects epigenetic/transcriptomic/biological aging, thus contributing to the rate of development of the co-occurring conditions in DS, with implications for these same common age-related conditions in the general population.
Down Syndrome Publications
Progress in brain research2020