Presbycusis Across the Lifespan: Genetic, Molecular, and Multi-Omics Contributions

Presbycusis, or age-related hearing loss (ARHL), is a multifactorial disorder characterized by a gradual, bilateral sensorineural decline in hearing sensitivity, predominantly affecting high-frequency sounds. It is one of the most common chronic conditions in the aging population and represents a major public health concern due to its high prevalence and progressive nature. Presbycusis significantly impairs speech perception, especially in noisy environments, leading to communication difficulties, reduced social participation, increased risk of social isolation, and a decline in quality of life. Moreover, growing evidence highlights a strong association between ARHL and cognitive impairment, dementia, depression, and increased frailty in older adults. The etiology of presbycusis is complex and involves the interplay between genetic predisposition and cumulative environmental and lifestyle-related factors. Genetic susceptibility influences cochlear aging, neural degeneration, and vulnerability to external insults. Non-genetic contributors include chronic noise exposure, cardiovascular and metabolic disorders such as diabetes and dyslipidemia, ototoxic medications, smoking, and other lifestyle factors that may accelerate cochlear damage through oxidative stress and microvascular dysfunction. This narrative review aims to provide an updated overview of the genetic and environmental determinants involved in the development and progression of presbycusis. Furthermore, it discusses the clinical implications of these factors for early identification, audiological evaluation, prevention strategies, and personalized management approaches. A better understanding of the multifactorial nature of presbycusis may support the development of targeted interventions to preserve hearing function and improve overall health outcomes in the aging population.