G4 in Aging at Organismal Level

National Institute On Aging

Investigators

Abstract

We will investigate the role of G4 in organismal aging using two models; mouse and fruit fly. For the mouse work, the aging cohort Study of Longitudinal Aging in Mice (SLAM) and mouse liver regeneration model will be utilized to address the hypothesis that expression of G4-resolving RECQ helicases declines with age concomitant with G4 accumulation, resulting in cellular and tissue-specific pathologies. The murine decline in G4 resolution with age will be assessed in rapidly proliferating tissues in which G4 DNA is thought to interfere with smooth DNA synthesis of replicating cells. In a second arm, we will examine consequences of G4 using Drosophila as a genetically tractable and ideal model for aging studies. Drosophila mutants deficient in the conserved G4-resolving helicase RTEL1 will be assessed for G4 accumulation and decreased. G4 accumulation will also be assessed for its consequences on mutagenesis of B lymphocytes during class switch recombination and in reproductive organ pathology where G4 nucleic acids are implicated in disease progression. The vast expertise of the assembled team of NIA collaborators ensures a promising outlook for the proposed studies.