Dietary Zinc Glycine Supplementation Attenuates Aging-Driven Cochlear Hair Cell Oxidative Injury and Hearing Loss.

Background

Micronutrient imbalance is now recognized as a modifiable risk factor driving the progression of age-related hearing loss (ARHL). Zinc, an indispensable dietary trace nutrient, acts as a structural cofactor and transcriptional regulator of a broad panel of antioxidant enzymes to sustain systemic and cellular antioxidant defense capacity. Nevertheless, the therapeutic value of zinc nutritional supplementation and its precise molecular mechanisms against age-dependent cochlear degeneration remain largely uncharacterized.

Methods

We established aging mouse models to observe the phenotypic changes caused by disrupted cochlear zinc nutritional homeostasis, and applied oral supplementation of bioavailable zinc glycinate to intervene in ARHL. In vitro D-galactose (D-gal) stimulation was adopted to induce cellular oxidative damage, followed by a series of mechanistic assays to detect the expression of core antioxidant molecules and determine mitochondrial function.

Results

Disrupted cochlear zinc nutritional homeostasis induced progressive hearing loss and severe hair cell degeneration in aging mice. Conversely, oral zinc glycinate supplementation significantly relieved age-related hearing decline and reduced oxidative injury of cochlear hair cells. As a nutritional intervention, zinc glycinate significantly elevates the levels of key intracellular antioxidants (SOD, GSH, and GPX4) and rescues mitochondrial dysfunction induced by D-galactose triggered reactive oxygen species accumulation. Moreover, the protective effect of zinc glycinate may be associated with the upregulation of metal-responsive transcription factor 1 (MTF-1), which in turn suppresses the D-galactose-induced hyperactivation of the pro-inflammatory cGAS-STING pathway.

Conclusions

Dietary zinc glycinate supplementation offers potential protection against cochlear aging. This auditory benefit may involve MTF-1 upregulation and inhibition of the cGAS-STING pathway. Collectively, these findings provide preclinical evidence supporting further investigation of zinc glycinate as a potential nutritional intervention for ARHL.