PROJECT SUMMARY/ABSTRACT Age-related hearing loss (ARHL) affects millions of individuals in the U.S. and is associated with devastating health and economic outcomes. A primary site of age-related auditory dysfunction is the cochlea. Cochlear aging begins as early as the fourth decade of life and stems from multiple etiologies. Therefore, early and differential diagnosis will be key for the success of current and future treatments for age-related cochlear dysfunction. However, current clinical tools are remarkably insensitive to early signs of aging in the auditory periphery. Our long-term goal is to fill this clinical void using otoacoustic emissions (OAEs). This project takes steps towards that goal by filling in critical gaps in knowledge that currently prevent OAEs from fulfilling their diagnostic potential. We do this by systematically exploring the aging cochlea using OAEs, with a focus on the underexplored cochlear base where age-related decline begins and where high frequencies are encoded. Our central hypothesis is that metabolic decline and increased irregularities (i.e., “roughness” due to random tissue degradation) in the cochlear base are the earliest signs of cochlear aging, and that these signs occur before they are detectable using current clinical measures (i.e., behavioral audiometry). We will test this hypothesis by pursuing three specific aims that explore cochlear function in ears of varying ages deemed normal by traditional measures. In Aim 1, we will characterize how age impacts the growth of two types of OAEs (distortion and reflection) through the highest frequency of human hearing (20 kHz). This dual-emission approach has proven promising in illuminating the mechanisms of age-related cochlear decline but has not yet been used to characterize aging through the cochlear base. In Aim 2, we will assess the influence of aging on the generation region of the same two types of OAEs. Understanding where OAEs arise along the cochlear partition and if they are impacted by basal regions of the cochlea (which we hypothesize decline in an early stage of aging) is crucial for both interpreting aging OAE patterns and for discerning the etiology of cochlear ARHL. In Aim 3, we will examine the relationship between the generation region of OAEs, perceptual tuning, and age. A key question is whether early signs of cochlear aging are detectable using perceptual measures not traditionally used in the clinic (e.g., psychophysical tuning). We will systematically probe the relationship between cochlear tuning estimates derived from distortion and reflection OAEs and psychophysical estimates of tuning and explore how these relationships change with age. Understanding this will be crucial for determining if retrocochlear filtering is significant in the aging ear, and for determining if OAEs may be used to assess cochlear tuning in aged ears. Collectively, this work will explore the use of otoacoustic emissions in detecting early age-related coc...