A recent collaborative study between Chinese and American scientists has unveiled a critical mechanism underlying age-related hearing loss, pointing to the potential repurposing of metformin, a widely used diabetes medication, to slow the progression of this common condition. The research, conducted on crab-eating macaques and published in the journal Nature Aging, highlights a gradual deficiency in the SLC35F1 protein—a key regulator in sensory receptor cells within the ear—as a hallmark of cochlear aging in primates, closely mirroring the human auditory system.
The study’s lead, Professor Wang Xi of Xuanwu Hospital affiliated with Capital Medical University in Beijing, emphasised the importance of using macaques due to their physiological similarity to humans, which improves the relevance of findings compared to previous rodent models. Leveraging advanced single-cell analysis, researchers mapped the cellular and molecular trajectories of cochlear aging at an unprecedented resolution. They discovered that reduced expression of the gene SLC35F1 leads to degeneration of sensory hair cells responsible for transforming mechanical sound vibrations into electrical signals for the brain, shedding light on a vital molecular trigger for hearing decline.
Additional experiments in mice reinforced the gene’s crucial role, as disabling SLC35F1 resulted in pronounced hair cell loss and hearing deficits. This positions SLC35F1 not only as a promising biomarker for early diagnosis but also as a potential therapeutic target. Importantly, older monkeys treated with metformin for over three years exhibited slowed cochlear aging and preserved hair cell numbers, suggesting metformin’s protective effects on the auditory system. Wang highlighted metformin’s established safety profile for diabetes, proposing it could accelerate clinical application in treating age-related hearing loss, though thorough clinical trials remain necessary.
These findings align with broader research exploring metformin’s role in delaying cellular senescence and neurodegeneration. Studies in auditory cells have shown that metformin reduces markers associated with senescence and enhances mitochondrial function by promoting mitophagy, therefore preventing premature cellular aging in the ear. Animal model investigations further support metformin’s otoprotective properties: it has been found to mitigate noise-induced hearing loss in rats, reduce neuronal apoptosis, and restore antioxidant balance, largely through regulating cellular stress responses and signalling pathways such as AMPK and ERK1/2.
Moreover, mechanistic insights reveal that metformin’s activation of AMP kinase and inhibition of pathways like the mevalonic acid pathway contribute to outer hair cell preservation, crucial for hearing sensitivity. These multidimensional protective effects position metformin as a highly promising candidate for therapeutically addressing the increasing global burden of age-related hearing impairment—a condition linked not only to communication difficulties but also to elevated risks of cognitive decline and dementia.
Moving forward, the research team plans to deepen their understanding of SLC35F1’s molecular role and to explore gene therapy or targeted interventions to complement pharmacological approaches. This initiative forms part of broader efforts by the Beijing Biogerontology Biomarker Alliance to develop comprehensive cochlear aging assessment systems, potentially enabling earlier detection and more effective management of hearing loss in aging populations.
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Source: Noah Wire Services
