Identification of pathways connecting age-associated accumulation of mtDNA mutations with aging phenotypes
A rich literature shows progressive accumulation of mitochondrial genome (mtDNA) mutations with age and implicates this accumulation in numerous late-onset diseases. Dr. Korotkevich’s research aims to uncover how such intra-organellar damage contributes to the development of aging symptoms in mice. She proposes that mtDNA mutations contribute to aging via stress signaling from compromised mitochondria that reverberates to the whole body. To test this idea, she will develop a method for simultaneous profiling of mtDNA mutations and gene expression in thousands of single cells. This approach will identify signaling pathways that are specifically affected in cells with high levels of deleterious mtDNAs. Dr. Korotkevich hopes that modulation of these pathways might defer onset of age-related degeneration.
