SIRT1 prevents noise-induced hearing loss by enhancing cochlear mitochondrial function.

Area of Science:

• Oto-neurology
• Molecular biology
• Genetics

Background:

• Noise-induced hearing loss (NIHL) is a prevalent condition with limited treatment options.
• Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, has a poorly understood role in NIHL pathogenesis.
• Understanding SIRT1's function is crucial for developing novel therapeutic interventions.

Purpose of the Study:

• To investigate the role of SIRT1 in the development of noise-induced hearing loss.
• To explore the molecular mechanisms underlying SIRT1's function in the cochlea following noise exposure.
• To evaluate the therapeutic potential of SIRT1 modulation for NIHL.

Main Methods:

• Utilized a mouse model of NIHL to assess changes in cochlear SIRT1 expression.
• Generated hair cell-specific SIRT1 knockout mice to study its function.
• Employed adeno-associated virus (AAV)-mediated SIRT1 overexpression in vivo.
• Performed transcriptomic analysis and in vitro studies on auditory cells (HEI-OC1) under oxidative stress.

Main Results:

• SIRT1 expression significantly decreased in the cochlea of NIHL mice.
• SIRT1 deficiency exacerbated hair cell damage, synaptic loss, and oxidative stress, worsening NIHL.
• SIRT1 overexpression attenuated noise-induced cochlear damage and alleviated hearing loss.
• SIRT1 deficiency impaired glucose metabolism and antioxidant pathways; SIRT1 activation promoted antioxidant effects via AMPK.

Conclusions:

• SIRT1 plays a critical protective role in the cochlea against noise-induced damage.
• SIRT1 is essential for maintaining redox balance and mitochondrial function post-noise exposure.
• Targeting SIRT1 represents a promising therapeutic avenue for managing noise-induced hearing loss.