Genomic Approaches to Understanding Metabolism and Aging

Yale University, New Haven CT

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Abstract

The aim of my research is to apply a genomics approach to understanding metabolic processes related to aging and diabetes. PGC-1alpha is a dynamic transcriptional coactivator that responds to various forms of metabolic stress and coordinates a response in a tissue-specific manner. For example, PGC-1 alpha has been implicated in regulating hepatic gluconeogenesis in response to starvation by interacting with selective transcription factors. Several of the factors that PGC-1 alpha interacts with are homologs of proteins that have been shown to influence the rate of aging in lower organisms. Polymorphisms in PGC-1 alpha have also been associated with type II diabetes, an age-related disease, in a variety of ethnically diverse populations. Based on these findings, I propose a project that involves utilizing the chromatin immunoprecipitation chip (ChIP chip) procedure on PGC-1 alpha and its interacting partners in conjunction with expression experiments in metabolically stressed mice to determine target genes that may influence metabolic processes central to aging and diabetes.