Cytosolic SINE retrotransposable element cDNA and mitochondrial DNA in aging retina

The project will (1) create temporal, spatial, and sequence topographic maps of Alu cDNA subfamilies and mtDNA in young, healthy aged, and AMD-affected human eyes; (2) probe the stimuli for and mechanisms of Alu cDNA generation in aging by investigating whether L1 regulators influence Alu cDNA production and retinal toxicity; and (3) elucidate the pathway of mitochondrial dysfunction triggered by Alu cDNA and the noncanonical inflammatory pathways triggered by Alu cDNA and mtDNA joint activity that are responsible for retinal cell death. This research will provide mechanistic insights into how cytosolic Alu cDNAs and mtDNA mediate interactions of aging hallmarks and modulate healthspan.