# Age, Injury, and the Neuromuscular Junction

> **NIH NIH K02** · UNIVERSITY OF MINNESOTA · 2024 · $149,904

## Abstract

Abstract
This application for an Independent Scientist Award (K02) is designed to advance knowledge important for
understanding mechanisms of age-related changes at the NMJ and support the career of Dr. Sarah M. Greising,
PhD, an Associate Professor in the School of Kinesiology at the University of Minnesota. As the elderly
population of the United States continues to increase there is an ongoing scientific necessity to understand the
causes of neuromuscular dysfunction in old age. Understanding neuromuscular dysfunction requires
fundamental evaluations of the neuromuscular junction (NMJ) the point of contact between a motor neuron and
skeletal muscle fiber. The NMJ initiates muscle contraction and allows physical movement including the ability
to breathe across the lifespan. Without innervation, muscle fibers cannot contract, significantly reducing function.
The overall objective of this K02 application is to characterize and correct neuromuscular deficiency and low
plasticity in the skeletal muscle following both aging and injury by evaluating if shared mechanisms of
destabilization of the NMJ exist. This proposal will capitalize on two pathologies that have limited regenerative
potential of skeletal muscle by evaluating the NMJ across the aging trajectory of mid- to old-age and following
volumetric muscle loss (VML), which is clinically identified as a chronic and irrecoverable loss of skeletal muscle
tissue resulting in functional impairments. Both aging and VML injury result in considerable neuromuscular
dysfunction, and chronic co-morbidities. My central hypothesis is that progressive NMJ destabilization in aged
and injured skeletal muscle create a hostile cellular environment in the muscle that mitigates plasticity and blunts
the effectiveness of interventions. I propose two specific aims to address these hypotheses: 1) To understand
the limits of diminished innervation and NMJ destabilization; and 2) To determine what spatial changes occur at
the NMJ during progressive destabilization. The results of the proposed studies will define cellular mechanisms
that contribute to the finite adaptive and regenerative capacity of the remaining muscle after injury and aging and
how this relates to NMJ destabilization. The stated goal of the K02 award is to foster the development of
outstanding scientists and enable them to expand their potential to make significant contributions to their field of
research. This K02 award will advance and reinvigorate Dr. Greising’s scientific development in aging biology
by providing protected time to: 1) to build preliminary data and a conceptual framework for a competitive NIA
R01-level grant proposal, 2) evaluate mechanisms of NMJ dysregulation in aged and injured skeletal muscle,
and 3) build my education and understanding of omics-based tools to develop collaborations able to ask and
answer impactful questions linking the physiology of the NMJ (my expertise) and these novel techniques
(collaborative expertise).

## Key facts

- **NIH application ID:** 10890161
- **Project number:** 5K02AG081488-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sarah M Greising
- **Activity code:** K02 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $149,904
- **Award type:** 5
- **Project period:** 2023-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890161

## Citation

> US National Institutes of Health, RePORTER application 10890161, Age, Injury, and the Neuromuscular Junction (5K02AG081488-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890161. Licensed CC0.

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