TARGETING NEURONAL FTL1 RESCUES COGNITIVE IMPAIRMENTS IN AGING

Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we report that ferritin light chain 1 (FTL1) is a pro-aging neuronal factor that impairs cognition. Targeting neuronal FTL1 in the hippocampi of aged mice elicits synaptic and metabolic-related molecular changes and rescues cognitive impairments. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation. Overall design: To better determine the effect of selectively targeting the age-related increase in neuronal FTL1, we generated aged temporally controlled neuron specific conditional Ftl1 genetic knockout mice (FTL1 cKO) using a viral-mediated in vivo CRISPR-Cas9 approach by delivering high-titer lentivirus encoding a Synapsin-driven Cre and guide RNA sequences into aged inducible Cas9 transgenic mice. We then performed expression profiling analysis using data obtained from nuclei RNA-seq of controls and Ftl1 cKP aged mice.