# Project 3:  Pathophysiology of human age-related hearing loss

> **NIH NIH P50** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $270,729

## Abstract

PROJECT SUMMARY/ABSTRACT – PROJECT 3
 Determining the mechanisms and site(s) of pathologies involved in age-related hearing loss is
challenging as they likely reflect a lifetime of environmental exposures, differences in susceptibility and co-
morbidities, and complex genetic factors. These individual differences may contribute to the large variation in
audiometric profiles and suprathreshold auditory function seen in older adults. In our Center, classification of
metabolic and sensory presbyacusis phenotypes is based on animal models linking specific cochlear deficits to
audiometric profiles, and has resulted in four cochlear-based phenotypes. Project 3 will refine these
phenotypes by developing and validating physiologic measures that predict cochlear and auditory nerve
pathology in older adults. Aim 3.1 tests the hypothesis that outer hair cell and cochlear lateral wall deficits
differentially contribute to sensory versus metabolic presbyacusis. Experiments in Aim 3.1 incorporate metrics
related to outer hair cell and stria vascularis function to predict cochlear pathologic site(s) and determine the
extent to which patterns of pathology are consistent with estimates of sensory and metabolic hearing loss. Aim
3.2 examines auditory nerve structure and function to test the hypothesis that changes in auditory nerve
activity result in unique and additive effects in auditory function of older adults. By using similar physiologic
assessments, experiments in Project 1 and Project 2 will provide a means to validate Project 3 results in
mouse models where the mechanisms and anatomical pathology are well defined. A significant advancement
in the characterization of underlying cochlear and neural pathologies of presbyacusis is crucial in developing
and testing new treatments as they become available, by appropriately assigning participants in clinical trials,
and in determining the best course of intervention for an individual. Moreover, individual differences in
pathophysiology identified in Project 3 are hypothesized to have differential effects on cortical representation
of speech and suprathreshold auditory processing, assessed in Project 4.

## Key facts

- **NIH application ID:** 10470233
- **Project number:** 5P50DC000422-34
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** KELLY C HARRIS
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $270,729
- **Award type:** 5
- **Project period:** 1997-07-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470233

## Citation

> US National Institutes of Health, RePORTER application 10470233, Project 3:  Pathophysiology of human age-related hearing loss (5P50DC000422-34). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10470233. Licensed CC0.

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