Aging-related hearing loss is growing at an alarming rate. Unfortunately, simple peripheral amplification devices, such as hearing aids, do not adequately treat this problem because they do not address the changes that occur at the level of the central nervous system. Although many previous investigators have examined the individual changes in tuning function, neurotransmitter pharmacology, temporal properties, etc., in the aging auditory system, what has been missing is an understanding of a unifying mechanism that ties these changes together. Herein, we propose to test the hypothesis that mitochondrial dysfunction underlies aging-related changes in physiological function, and that there may be metabolic ?hubs? in the auditory system that are particularly vulnerable during aging. To answer this question, we will employ an endurance exercise intervention in a population of mice that have been genetically engineered to age prematurely and examine the impact of exercise on brain metabolism at multiple levels of the central auditory system simultaneously. We hypothesize that particular portions of the central auditory system will be selectively vulnerable to aging-related changes, and that 1) endurance exercise will mitigate these changes and 2) upregulation of PGC1?, a transcriptional coactivator critical for mitochondrial biogenesis, is associated with the protective effects of exercise. Successful completion of this work will not only shed light on basic mechanisms involved in aging, but will also reveal new therapeutic targets to augment the beneficial effects of endurance exercise on the central auditory system.
We propose that a unifying mechanism that ties together both peripheral (i.e., inner ear) and central (i.e., brain) components of aging-related hearing loss is the loss of cellular energy production that occurs with aging. Therefore, in this research we examine the effects of exercise on regions of the brain important for hearing in a group of genetically-modified mice who age prematurely. Successful completion of this work will unveil new treatment targets to diminish the growing numbers of those with aging-associated hearing loss.
