# Presynaptic active zone alterations that underlie dynapenia at aged mouse neuromuscular junctions

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $250,000

## Abstract

Project Summary/Abstract:
The over-65 population is growing, and over 1/3 of aged people will experience a fall. Falls in
the elderly often result from frailty caused by muscle weakness, balance deficits, and gait
instability. Previously, these deficits were ascribed to declining muscle mass (sarcopenia),
however, simply increasing muscle mass does not necessarily rescue age-induced functional
deficits. The term dynapenia has been introduced to denote aging-induced loss of muscle
strength, which includes deficits in motoneuron excitability, motor unit recruitment, transmitter
release at the neuromuscular junction (NMJ), and muscle mass and function. As such, it is
critical to fully understand the changes that occur within NMJs to identity new targets for therapy
development. Here, we propose to define heterogeneous changes that occur within the
transmitter release sites (active zones; AZs) within NMJs that underlying dynapenia in an aged
mouse model. Specifically, we will (1) use a combination of electrophysiology and a new optical
quantal analysis approach we developed to study changes in the control of transmitter release
within single identified NMJs during aging, (2) use a new super-resolution imaging approach of
the density and distribution of presynaptic voltage-gated calcium channels within single AZs and
compare these results with our single AZ optical measurements of transmitter release in
identified NMJs over the aging time course, and (3) use a realistic computer simulation to test
the hypothesis that age-induced changes in AZ voltage-gated calcium channel density and
distribution predict single AZ and whole synapse function at the aging NMJ. The results from
these aims will elucidate the detailed structural and functional changes that occur within
transmitter release sites (AZs) of aging NMJs over the time course of the dynamic alterations
that occur as dynapenia develops. This information will guide future studies aimed at targeting
these specific aging-induced changes with the goal of treating dynapenia.

## Key facts

- **NIH application ID:** 11127992
- **Project number:** 3R01AG083078-02S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** STEPHEN D MERINEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2023-09-30 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11127992

## Citation

> US National Institutes of Health, RePORTER application 11127992, Presynaptic active zone alterations that underlie dynapenia at aged mouse neuromuscular junctions (3R01AG083078-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11127992. Licensed CC0.

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