# Determinants of age-induced hearing loss and reversal strategies

> **NIH NIH P01** · UNIVERSITY OF NEVADA RENO · 2020 · $1,581,680

## Abstract

Abstract
 Age-related hearing loss (ARHL) or presbycusis is the most prevalent sensory deficit and with the increase in
life expectancy, it is predicted to have vast impact in the well-being of our society. Indeed, audition and
communication is the essence of our human interactions. The overall framework for this programmatic proposal
is that a comprehensive understanding of ARHL is only possible through studies of not only the vulnerable
synaptic and neural structures of the inner ear, but also examination of the neural plasticity that occurs in
response to changes at the neurites of spiral ganglion neurons. We have brought together expert individuals
from genetics to cell biology and physiology (Tempel, Yamoah, Ricci, and Gratton). These investigators have
already worked together in a highly synergistic and productive manner.
 There are three projects (P) served by three Cores (Administrative, Mouse Genetics and Structural Analysis
Cores) to test the Central Hypothesis that the aging auditory sensory epithelia undergo structural changes that
allow the high K+ endolymph to leak into the perilymph, triggering HC and SGN depolarization, increased
intracellular Ca2+ ([Ca2+]i) and subsequent “silent” synaptic and neuronal degeneration (P2, P3). We predict
that structural changes are mediated by weakening tight junctions (TJs) in the aging cochlear sensory
epithelium (P1, Core C). Genetic manipulation of Claudin 9 and Occludin, two identified TJ proteins in the
sensory epithelium, that show robust reduction in expression levels, will be used as prototypes together with
three additional ARHL models to test our hypothesis (P1-3, Cores B-C). We propose that neural and synaptic
alterations at the periphery (P2, P3) will mediate cellular changes that confer long-lasting alterations auditory
system. The proposed studies will reveal critical neural and synaptic mechanisms of ARHL. New therapeutic
targets for the treatment of ARHL will be assessed, tested and proposed, thus, transforming and shifting the
prevailing paradigm to mechanistic and translational platforms.

## Key facts

- **NIH application ID:** 9969292
- **Project number:** 5P01AG051443-05
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** EBENEZER N YAMOAH
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,581,680
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969292

## Citation

> US National Institutes of Health, RePORTER application 9969292, Determinants of age-induced hearing loss and reversal strategies (5P01AG051443-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9969292. Licensed CC0.

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