NMNAT1 Activates Autophagy to Delay D‐Galactose‐Induced Aging in Cochlear Hair Cells

) levels and impaired autophagy; however, the mechanisms underlying these processes remain largely unclear. In our study, we assessed the role of nicotinamide nucleotide adenylate transferase 1 (NMNAT1) in cochlear hair cell aging using D-galactose (D-gal)-induced aging HEI-OC1 cells and cochlear explants. We observed a significant reduction in NMNAT1 expression in HEI-OC1 cells and cochlear hair cells treated with D-gal. Notably, NMNAT1 overexpression activated autophagy and decelerated hair cell aging. Metabolomic analysis revealed a dysregulated tricarboxylic acid cycle in Nmnat1-knockout cells, indicating that NMNAT1 regulates autophagy and metabolic pathways that affect hair cell aging. These findings offer novel insights into the association between autophagy and metabolism during aging and highlight NMNAT1 as a potential therapeutic target for the prevention and treatment of ARHL.