2. Academic Validation
  3. NMNAT1 Activates Autophagy to Delay D-Galactose-Induced Aging in Cochlear Hair Cells

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

  • Aging Cell. 2026 Feb;25(2):e70373. doi: 10.1111/acel.70373.
Yongjie Wei 1,  Wenqing Yang 1,  Han Wu 1,  Mengdie Kong 2,  Dachuan Fan 1,  Yuhua Zhang 1,  Nan Cheng 1,  Jiawei Du 1,  Lingna Guo 1,  Yuyang Li 1,  Ye Zhang 3,  Qian Dai 4,  Wei Cao 1,  Jianming Yang 1,  Qiaojun Fang 1
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 2 School of Life Science and Technology, Southeast University, Nanjing, China.
  • 3 Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 4 School of Life Sciences, Anhui Medical University, Hefei, China.
PMID: 41521645 DOI: 10.1111/acel.70373
Abstract

With an aging population, the incidence of age-related hearing loss (ARHL) continues to increase. Aging cells exhibit reduced nicotinamide adenine dinucleotide (NAD+) 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.

Keywords

NMNAT1; TCA cycle metabolism; age‐related hearing loss; autophagy; cochlear hair cell.

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