Modeling the Aging Epigenome

One of the important unanswered questions in biology is what determines how fastwe age. Aging in all species follows a stereotypical set of changes, but the rate can be highly variable.Genes that regulate the rate of aging and onset of age-related disease have received considerableattention, but the epigenetic contribution to this process remains a mystery. This relates in part to thecomplexity of the epigenome in vivo, and the difficulty encountered when attempting to interpret epigeneticchanges in heterogeneous cell populations. This is a significant barrier to epigenetic analysis in complextissues and model organisms that cannot be readily dissociated into individual cell types. To address thisbasic issue, we are developing a new approach for targeted epigenetic analysis in identified cell types, usingthe nematode worm C. elegans and the mouse as model systems. The aims are: 1. To develop a targetingsystem in C. elegans for isolating nuclei or chromatin from specific cell types in vivo, enabling epigeneticanalysis at cell-type resolution. This approach will be utilized to investigate the role of cell type-specificepigenetic changes in the aging process. 2. To develop a mouse model for epigenetic analysis of specificcell types in any adult tissue. This approach will be utilized to investigate epigenetic changes associatedwith brain aging and neurodegeneratio