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.