Long-term treatment with aldosterone slows the progression of age-related hearing loss

Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent
chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from
some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in
significant declines in workplace productivity, quality of life, cognition and abilities to communicate
effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role
in the maintenance of key ion pumps, including the Na-Kþ-Cl co-transporter 1 or NKCC1, which is
involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone
(1 mM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not
dose-dependent (dosing range from 1 nM to 100 mM). In the current study we measured behavioral and
electrophysiological hearing function in middle-aged mice following long-term systemic treatment with
aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1
protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a
functional measure of hearing, and the auditory brainstem response was used as an objective measure of
peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological
measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of
aldosterone on age-related hearing loss and pave the way for translational drug development, using
aldosterone as a key component to prevent or slow down the progression of ARHL.