Metabolic Shifts in Murine Inner Ears Mimicking Erythrocytes and Plasma Reveal Diagnostics and Early Predictors for Age-Related Hearing Loss

Authors

Qi Guo
Zhenjiang Li
Cheng Luo
Changhan Chen
Xi Long
Yidan Wang
Qingfen Qiang
Fang Yu
Wuping Liu
Yujin Zhang
Rodney E Kellems
Yang Xia

Language

English

Publication Date

9-19-2025

Journal

iScience

DOI

10.1016/j.isci.2025.113285

PMID

40949103

PMCID

PMC12424239

PubMedCentral® Posted Date

8-5-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Age-related hearing loss (ARHL) is a major public health concern, driven by the interplay of multiple factors. Here, we reveal spatiotemporal metabolic shifts in murine inner ears mirroring erythrocytes and plasma. Isotope-labeled glucose tracing demonstrates a metabolic rerouting favoring glycolysis over the pentose phosphate pathway, alongside downregulation of the tricarboxylic acid cycle, indicating impaired energy production and redox homeostasis. Accumulation of medium- and long-chain acylcarnitines further exacerbates lipotoxicity. Notably, age-dependent depletion of arginine, lysine, proline, and glycine disrupts the arginine-polyamine-urea cycle. Translationally, UK Biobank plasma metabolomics links omega-6 fatty acids, linoleic acid, glycine, and albumin to ARHL resilience, while branched-chain amino acids, tyrosine, creatinine, glycoprotein acetyls and urea confer risk. Sex differences in ARHL were linked to fatty acid metabolism divergence. These bioenergetic disruptions in the inner ear are mirrored in erythrocytes and plasma, highlighting potential biomarkers for early ARHL diagnosis and treatment.

Keywords

Diagnostics, Human metabolism

Published Open-Access

yes

Recommended Citation

Guo, Qi; Li, Zhenjiang; Luo, Cheng; et al., "Metabolic Shifts in Murine Inner Ears Mimicking Erythrocytes and Plasma Reveal Diagnostics and Early Predictors for Age-Related Hearing Loss" (2025). Faculty, Staff and Student Publications. 5961.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5961