Hearing loss related to aging (presbyacusis) is one of the major disorders affecting the elderly, yet we know very little about what causes the changes that occur in the auditory system and how these relate to hearing loss. Is human presbyacusis simply an aging of auditory structures, is it aging plus the summing of a lifetime of ototraumatic insults from noise, chemicals (drugs), and disease or are other factors such as changes in blood flow, increased free radical formation, genetically programmed neuronal cell death, increased susceptibility to noise or chemical damage or even diet significant? Is human presbyacusis not the result of "pure aging" of auditory structures and this the reason no adequate animal model has been found? We have established a collaborative effort between the laboratories of anatomy, biochemistry and physiology of the Kresge Hearing Research Institute to elucidate mechanisms involved in the development of auditory sensory deficits in aging. We will perform morphological and neurochemical assessments in guinea pig and rat to test the following hypotheses: 1) That age-related loss of spiral ganglion cells and changes in inhibitory and excitatory circuitry in auditory brainstem and cochlea occur independently of changes in organ of Corti, 2) That there are age- related changes in cochlear blood flow, cochlear vessels and cochlear vascular reactivity, 3) That changes in the sensitivity of cochlear hair cells to ototraumatic insults occur with aging, 4) That free radical accumulation induces changes in lipid peroxidation, membrane lipid domains, membrane fluidity and function in aging, and 5) That increased fat and/or cholesterol diet influences the age-related changes listed above. Physiological assessments of auditory function will be performed for correlation with these parameters. This will provide us with information that will help us not only to better understand the origins and development of hearing loss in the elderly, but, to develop more effective methods of its treatment and prevention.