Serum metabolomic profiling identifies a biomarker panel associated with age-related hearing loss

Age-related hearing loss (ARHL) is a progressive neurodegenerative disorder for which reliable biomarkers are lacking. This study aimed to identify serum metabolic markers associated with ARHL that may improve early screening and diagnostic performance. A total of 300 subjects, including 125 healthy controls and 175 patients with ARHL from three independent centers, were enrolled. Untargeted and targeted metabolomics based on liquid chromatography–quadrupole time-of-flight mass spectrometry were performed to characterize metabolic alterations. Multivariable regression analysis was used to examine metabolite–phenotype associations, and logistic regression combined with receiver operating characteristic curve analysis evaluated diagnostic performance. Ten candidate metabolites were initially identified. Stepwise regression analysis demonstrated that d -glutamine (OR 1.81, 95% CI 1.29–2.53), sphingomyelin (d18:1/20:0) (OR 1.24, 95% CI 1.12–1.37) and N6-methyladenosine (OR 1.22, 95% CI 1.09–1.42) were independently associated with ARHL after controlling for age, sex, body mass index, smoking status, triglycerides and high-density lipoprotein cholesterol. The validation cohort confirmed that the biomarker panel exhibited strong diagnostic potential for ARHL (AUC 0.8523, 95% CI 0.7429–0.9704). These findings identify and validate a serum metabolomic signature for ARHL, providing new insight into early detection and clinical assessment of ARHL.