Age Related Hearing Loss and Vestibular Dysfunction

Proposed studies are to test mechanism-based, clinically relevant interventions to meet the challenges of
aging in the Veteran population. Hearing Loss is one of the most common service-related disabilities for those
who served in the gulf wars and age-related hearing loss (ARHL) contributes to this. Our current studies in the
mouse model found that rapamycin significantly delayed / reduced ARHL. Our preliminary now show potential
for 17-α-estradiol as another treatment option that acts on a different functional signaling pathway. Aim 1A will
test 17-α-estradiol treatment for ARHL and Aim 1B will examine if a combination of rapamycin and 17-α-
estradiol treatments increases overall efficacy over either alone.
Noise and Aging are the two most common causes of hearing loss and for many Veterans ARHL will
superimpose on an auditory system already compromised by noise exposure during their service. Our current
studies found that noise exposure during youth significantly accelerated and increased ARHL and our pilot
studies suggest rapamycin treatment starting shortly after the noise exposure can significantly reduce this
noise enhancement of ARHL. Aim 1C will test efficacy of rapamycin treatment starting later in life (more
pertinent to treatment of Veterans) shortly before noise acceleration would appear.
Balance and gait disorders effect millions of Americans and become worse with aging. We hypothesize that
inner age aging disorders share sufficient underlying mechanisms such that the treatments we have shown
to delay / reduce ARHL will also delay / reduce age-related vestibular dysfunction (ARVD). This is tested in
Aim 2A. Aim 2B will test if noise overstimulation given in youth will have a comparable influence on ARVD
as we see with ARHL, and result in an acceleration and enhancement of age-related vestibular
dysfunction. This would lead to later studies testing treatments.

Grant Number: 5I01RX004226-03
NIH Institute/Center: VA
Principal Investigator: Richard Altschuler