Age-related hearing loss in Mn-SOD heterozygous knockout mice

Area of Science:

• Otolaryngology
• Gerontology
• Mitochondrial Biology

Background:

• Age-related hearing loss (AHL) significantly impacts elderly quality of life.
• Manganese superoxide dismutase (Mn-SOD) is a key mitochondrial antioxidant enzyme scavenging reactive oxygen species (ROS).
• The role of reduced Mn-SOD in accelerating AHL is not fully understood.

Purpose of the Study:

• To investigate if a reduction in Mn-SOD accelerates age-related hearing loss.
• To evaluate auditory function and cochlear changes in Mn-SOD heterozygous knockout mice compared to wild-type controls.

Main Methods:

• Auditory function was assessed using auditory brainstem response (ABR) in Mn-SOD heterozygous knockout (HET) and wild-type (WT) mice at 4 and 16 months of age.
• Histological analysis included evaluation of hair cell loss, spiral ganglion cell density, and stria vascularis thickness.
• Immunoreactivity for oxidative stress markers 8-hydroxydeoxyguanosine and 4-hydroxynonenal was assessed.

Main Results:

• Both WT and HET mice showed increased ABR thresholds at 16 months compared to 4 months, indicating age-related changes.
• No significant differences in ABR thresholds, hair cell loss, spiral ganglion cell density, or stria vascularis thickness were observed between HET and WT mice at either age.
• Increased 8-hydroxydeoxyguanosine immunoreactivity was noted in HET mice at 16 months, suggesting some increase in oxidative stress, but 4-hydroxynonenal levels did not differ.

Conclusions:

• A partial reduction in Mn-SOD (by half) increases oxidative stress in the cochlea to a limited extent.
• This increase in oxidative stress is not sufficient to accelerate age-related cochlear damage or hearing loss during physiological aging.
• Mn-SOD deficiency alone may not be a primary driver for accelerated age-related hearing loss under normal aging conditions.