DNA polymerase kappa (POLK) progressively relocates from the nucleus to the cytoplasm in aging mouse neurons, with this redistribution serving as a predictor of brain tissue age. Nuclear POLK levels decline significantly with chronological aging while cytoplasmic accumulation increases, coinciding with elevated DNA damage markers. GABAergic interneurons show higher baseline nuclear POLK expression compared to excitatory neurons, reflecting differences in metabolic demands and firing rates. This subcellular mislocalization represents a fundamental breakdown in neuronal DNA repair capacity during aging. The finding illuminates why postmitotic neurons become increasingly vulnerable to genomic instability over time, as POLK normally facilitates repair of damaged DNA that cannot be resolved through standard replication mechanisms. Unlike dividing cells that can dilute damage through cell division, neurons must maintain their genomes indefinitely, making efficient DNA repair systems critical for longevity. The cytoplasmic accumulation with stress granules suggests POLK sequestration away from its nuclear repair function. This research provides a mechanistic explanation for age-related neurodegeneration and suggests that maintaining proper POLK nuclear localization could be a therapeutic target for preserving cognitive function and extending healthspan.