Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Abstract

Mitochondrial DNA (mtDNA) damage is associated with the development of cardiovascular diseases. Cardiac aging plays a central role in cardiovascular diseases. There is accumulating evidence linking cardiac aging to mtDNA damage, including mtDNA mutation and decreased mtDNA copy number. Current wisdom indicates that mtDNA is susceptible to damage by mitochondrial reactive oxygen species (mtROS). This review presents the cellular and molecular mechanisms of cardiac aging, including autophagy, chronic inflammation, mtROS, and mtDNA damage, and the effects of mitochondrial biogenesis and oxidative stress on mtDNA. The importance of nucleoid-associated proteins (Pol γ), nuclear respiratory factors (NRF1 and NRF2), the cGAS-STING pathway, and the mitochondrial biogenesis pathway concerning the development of mtDNA damage during cardiac aging is discussed. Thus, the repair of damaged mtDNA provides a potential clinical target for preventing cardiac aging.