Age-related hearing loss (ARHL) refers to the gradual loss of auditory sensitivity over the lifespan associated with aging. In humans, it is a complex health issue with multiple impactful factors, including noise exposure, disease, drug effects, genetics, and factors associated with normal aging of tissues. ARHL is one of the most common health disorders associated with aging in humans, affecting almost half of all adults in the United States by the age of 70, and over 80% of adults by age 85 (Lin et al., 2011). ARHL in humans commonly manifests functionally as impaired high-frequency hearing, poor speech understanding along with impaired signal-to-noise discrimination and slowed central auditory system processing (Profant et al., 2020; Syka, 2002).

ARHL can result from changes in both peripheral and central auditory systems (CAS) (Frisina and Walton, 2001). Peripheral changes include loss of cochlear hair cells (Mcgill and Schuknecht, 1976), deterioration in the stria vascularis and spiral ligament leading to a decrease in endocochlear potential (EP) (Engle et al., 2013; Nelson and Hinojosa, 2006; Ohlemiller, 2009; Ohlemiller et al., 2006) and degeneration of the spiral ganglion cells and cochlear nerves (Bao and Ohlemiller, 2010; Johnsson and Hawkins, 1972; Schuknecht, 1964). Centrally, age-related changes in GABA-mediated inhibitory transmission has been reported in the inferior colliculus (Caspary et al., 2008; Caspary et al., 1995; Milbrandt et al., 1994) and auditory cortex (Caspary et al., 2008). Gross anatomical changes such as cell number and volume depend strongly on the structure investigated, animal genotype and type of cell. For instance, the anterior ventral cochlear nucleus of C57 mice shows little changes in cell density, number and volume with age, whereas CBA/J mice do show a modest decline in cell number but only at extreme age (Willott et al., 1992; Willott et al., 1987). Some of these central and midbrain changes are likely the result of altered input from a malfunctioning cochlea resulting in compensatory neural plasticity (Frisina and Walton, 2001; Schrode et al., 2018; Willott et al., 1993).

Mice have become the predominant model organism for hearing research in general, and ARHL in particular (Bowl and Dawson, 2015; Ohlemiller et al., 2016). The CBA/CaJ strain specifically has become a standard model for ARHL as it exhibits only a moderate decrease in hearing sensitivity over most of its lifespan, closely resembling human ARHL (Zheng et al., 1999). Hearing sensitivity in animal models is frequently evaluated using the auditory brainstem response (ABR) to determine thresholds, which indicate the minimal intensity at which a response to an acoustic stimulus can be detected. Both cross-sectional and longitudinal ABR surveys have been used to characterize auditory sensitivity in aging mice, showing that hearing thresholds generally increase with age along with measures of cochlear dysfunction, such as hair cell loss (Spongr et al., 1997), cochlear nerve envelope responses (CNER) (Henry, 2002), distortion-product otoacoustic emissions (DPOAE) (Guimaraes et al., 2004) and EP (Ohlemiller et al., 2006). However, it is notable that not all measures of cochlear function correlate with ABR threshold changes. For instance in C57BL/6J (C57) mice EPs remain elevated until over 2 years of age (Ohlemiller et al., 2006), well after hearing thresholds suggest the mouse is functionally deaf. Additionally, CNERs in C57s show disruption before changes in ABR threshold are seen (Henry, 2002). DPOAEs also exhibit age- and strain-dependent differences, but typically these parallel auditory threshold changes (Martin et al., 2007). CBA/CaJ mice display minor changes out to 15 months, while C57 mice show distinct changes at 5 months of age (Jimenez et al., 1999). Regardless of cochlear physiological changes, the response of the brainstem CAS to auditory input is an integration of peripheral and central function and may be the most pertinent objective indication of whether the animal can adequately detect a sound. Therefore, the ABR threshold has a utility for evaluating hearing capability at all stages of an animal's life.

To improve the utility of the CBA/CaJ mouse model of ARHL, a detailed database needs to be available with respect to ages tested and thoroughness of data on hearing thresholds in this strain. While valuable reports of hearing loss in the CBA/CaJ mouse at various ages have previously been published, some lacunae persist in the complete characterization of CBA/CaJ hearing over its entire lifespan. For instance limitation to only female mice (Li and Borg, 1991) or limited age-range (Henry, 2004; Kobrina et al., 2020). Another important factor is that earlier influential studies on aging in CBA-type mice used the CBA/J strain, which show different auditory ageing characteristics than the CBA/CaJ (Ohlemiller et al., 2010). To fill in these gaps we took advantage of the accumulation of ABR records in the same laboratory over several years, using the same mouse strain and technology, providing a comprehensive database of auditory thresholds in experimentally naïve mice. This database also comprised records from a large age range of mice, allowing fine temporal resolution of hearing acuity over nearly the complete lifespan of a CBA/CaJ mouse.