The major issue addressed by the proposed research is the question of whether the tempo and the severity of auditory cellular changes are altered in animals whose lifespans are prolonged beyond conventional limits. The research proposed will achieve this prolongation of lifespan by means of chronic food restriction, using a regimen that does not in and of itself lead to debility or deficiency. The work employs anatomical and functional techniques, correlated with observations of organ and systemic pathology, to examine rats whose lifespans are extended well beyond normal limits. The rationale underlying the work involves (1) assessment of the value of lifespan extension from the standpoint of neural preservation, and (2) establishment of an important new model for aging research. The specific system to be examined is the auditory system, a system which, in humans, exhibits marked and reliable functional and structural degradation with advancing age. The observations will focus on the two ends of the auditory pathway, the cochlea and auditory cortex. Using light and electron microscopy, age- related changes will be analyzed in the sensory hair cells, synapses, spiral ganglion cells, stria vascularis, and blood vessels of the cortex. The cortical analysis will include the use of Golgi deimpregnation techniques to permit ultrastructural examination of specifically identified cortical cell types. The results will be closely correlated with the results of brainstem auditory evoked responses, and the findings interpreted in the light of analyses of organ system pathology. Among the major hypotheses to be tested are the following: (1) the absolute length of the lifespan is a significant variable in extent of age-related cellular change; (2) changes in restricted rats occur at normal tempo, but are more severe than those in ad lib. fed rats.
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