Hyaluronan gene transfer boosts mouse healthspan but spares hearing
Researchers created mice expressing naked mole rat hyaluronan synthase 2, which produces very high molecular weight hyaluronan. These mice showed improved healthspan and longevity, but no benefit for age-related hearing loss, unlike calorie restriction. The finding suggests distinct mechanisms for these interventions in the cochlea.
The study builds on prior work showing that naked mole rats produce unusually large hyaluronan molecules, a trait thought to contribute to their exceptional longevity and disease resistance. By engineering C57BL/6 mice to express the naked mole rat version of hyaluronan synthase 2, researchers created a lineage that produces very high molecular mass hyaluronan throughout the body, including within the cochleae.
While these transgenic mice demonstrated broad health benefits—improved healthspan, reduced inflammaging, and extended lifespan—their hearing declined at a rate comparable to normal mice. This stands in contrast to calorie restriction, which has been shown to protect against age-related hearing loss in the same strain. The divergence suggests that the mechanisms by which hyaluronan and calorie restriction influence aging differ within the cochlea.
The decoupling of healthspan benefits from hearing preservation could reshape how researchers approach age-related hearing loss therapies. If hyaluronan-based interventions prove ineffective for auditory decline, drug developers may need to pursue separate strategies targeting cochlear aging specifically. Given that roughly one in three older adults experiences hearing difficulty, the distinction between systemic and organ-specific aging mechanisms could influence future clinical priorities. However, these findings remain preliminary, and translation from mouse models to human therapies would require substantial further investigation.