NAD(+) Metabolism in Age-Related Hearing Loss.

Age-related hearing loss (ARHL), a degenerative disorder characterized by age-dependent progressive increase in the threshold of auditory sensitivity, affects 40% of people over the age of 65, and it has emerged as an important social and public health problem. Various factors, including genetic and environmental components, are known to affect both the onset and severity of ARHL. In particular, age-dependent changes in cellular oxidative stress and inflammatory responses accompanied by altered cellular signaling and gene expression progressively affect the function of the auditory system and eventually lead to hearing impairment. Recent findings suggest that a disturbance of intracellular NAD(+) levels is clinically related to the progression of age-associated disorders. Therefore, maintenance of optimal intracellular NAD(+) levels may be a critical factor for cellular senescence, and thus, understanding its molecular signaling pathways would provide critical insights into the prevention and treatment of ARHL as well as other age-related diseases. In this review, we describe the role of NAD(+) metabolism in aging and age-related diseases, including ARHL, and discuss a potential strategy for prevention or treatment of ARHL with a particular interest in NAD(+)-dependent cellular pathways.