Sirt1/Lxrα Signaling Pathway is Involved in Age-Related Hearing Loss in C57bl/6j Mice and its Mechanism

Abstract

Age-related hearing loss (ARHL) is the most prevalent form of hearing impairment and a significant neurodegenerative condition associated with aging. Silent information regulator 1 (SIRT1), a key enzyme involved in diverse physiological processes, has demonstrated protective effects against multiple age-related diseases. The liver X receptor (LXR), a nuclear receptor regulating cholesterol homeostasis and macrophage activity, is also implicated in aging-related conditions. Both SIRT1 and LXR have been associated with ARHL. Although SIRT1 is an upstream regulator of LXRα and is known to be expressed in the cochlea and auditory cortex of C57BL/6J mice, the presence of LXRα in cochlear tissues and its involvement in the SIRT1/LXRα signaling pathway during ARHL remains unreported. This study aimed to investigate the expression levels of SIRT1 and LXRα in the inner ear and examine their relationship with cochlear morphology. We assessed hearing function in mice at different ages and analyzed age-related changes in cochlear histopathology and protein expression. Our goal was to elucidate the role of the SIRT1/LXRα signaling pathway in the pathogenesis of ARHL, explore its cellular and molecular mechanisms, and identify potential targets for the prevention and treatment of ARHL.

Note:
Funding declaration: The study was sponsored by Science and Technology Program of Guangdong province (2018A070706003) and Science and Technology Program of Guangzhou City (202002030486). The sponsor or funding organization had no role in the design or conduct of this research.

Conflict of Interests: None of the authors has a conflict of interest to declare.

Ethical Approval: The animal study was reviewed and approved by Animal Ethics Committee of the Third Affiliated Hospital of Southern Medical University.

Keywords: Age-related hearing loss, Sirtuin 1, Liver X receptor, Cochlea