The naked mole-rat nmrHas2 gene failed to protect mice from age-related hearing loss
The naked mole-rat nmrHas2 gene failed to protect mice from age-related hearing loss
On August 27, in a study published in Frontiers in Aging, researchers compared female C57BL/6 laboratory mice carrying the naked mole-rat nmrHas2 gene with a control group. By 12 months, hearing had deteriorated in all animals, and the groups showed no statistically significant difference in their ABR hearing thresholds, which measure the lowest sound level that still produces a response in the auditory system.
nmrHas2 encodes an enzyme that produces hyaluronan, a long molecule found in the extracellular matrix. Naked mole-rats produce a particularly large form of hyaluronan. In a 2023 study, mice carrying the same gene had a 4,4% increase in median lifespan and a 12,2% increase in maximum lifespan. The authors also observed less age-related inflammation. The new experiment tested whether this intervention also preserved a specific function during aging.
The authors selected C57BL/6 mice because this laboratory strain develops age-related hearing loss relatively early. They activated the added gene with tamoxifen at one month and measured hearing by ABR at three and twelve months. ABR records the electrical responses of the auditory nerve and brainstem to clicks and tones at different frequencies. The threshold is the quietest sound that still produces a response.
The main comparison included eight transgenic and nine control females at twelve months of age. The researchers found no differences in hearing thresholds for clicks or tones at six frequencies, from 4 to 32 kHz. They detected nmrHas2 RNA in the cochlea, a part of the inner ear, of the transgenic mice, confirming that the added gene was being transcribed in this tissue. The experiment therefore tested separately whether the genetic construct was active in ear tissue and whether hearing was preserved.
The authors propose two hypotheses. The Cdh23 variant found in C57BL/6 mice is associated with early age-related hearing loss and may have weakened the effect of the intervention. They also suggest that the cochlea may have accumulated too little of the particularly large form of hyaluronan. Comparisons with a mouse strain in which hearing declines for a different reason, or with models of noise-induced and drug-induced damage, could help distinguish between these explanations.