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.