# Social Isolation and Loss of Physical Function: Defining a Novel Neuromuscular Phenotype

> **NIH NIH R03** · OHIO STATE UNIVERSITY · 2020 · $78,000

## Abstract

Summary of the proposed research
 Loss of physical function is a major public health problem that is associated with diminished quality of
life, increased risk for disability, and increased healthcare costs. Sarcopenia, or pathological age-related muscle
wasting and weakness, is a major contributor to loss of physical function in older individuals. Motor neurons
represent the final common output for the central nervous system by converting descending inputs into forces
by activating muscle contraction via neuromuscular junctions. Our prior work has demonstrated that aged mice
have striking features of motor neuron dysfunction and loss of connectivity with muscle and that motor neuron
connectivity is tightly associated with muscle size and function in aged mice. Our proposal is based on the
following scientific premises supported by prior research and our recent preliminary data: 1. Loss of motor neuron
connectivity with muscle is a driving force leading to age-related loss of muscle function, 2. Loss of muscle
function is a major contributor to loss of physical function, and 3. Stress can exacerbate or accelerate the effects
of aging on motor unit connectivity. Our recent data demonstrate that social isolation in aged mice results in
accelerated losses of motor unit connectivity at the neuromuscular junction. Our prior work demonstrated that
aged mice exhibit loss of NMJ transmission at 27 months. Following one month of single housing (one mouse
per cage) 22-month-old mice show accelerated NMJ failure typical not seen until 27 months. The aims of the
current proposal will investigate our novel findings of a link between social isolation and age-related loss of NMJ
transmission. Aim 1 of the proposal will test the hypotheses that social isolation-accelerated loss of physical
function is age- and sex-dependent. To achieve this aim, we will compare both group and single housed mice at
three ages: 6, 15, and 22 months. Groups will be balanced for male and female mice to compare effects between
genders. Based on preliminary data, it is predicted that: 1. Social isolation-accelerated loss of physical function
will be evident in 15- and 22-month-old mice but not 6-month-old mice. Aim 2 will determine the
pathophysiological mechanism of NMJ transmission failure following social isolation. Recent work has
highlighted the importance of sympathetic innervation of the NMJ for maintenance of synaptic integrity and
presynaptic acetylcholine release. Based on these findings and the fact that stress impacts sympathetic tone,
we predict that social isolation may impact sympathetic function at the NMJ and thus result in presynaptic NMJ
transmission failure. The results of these studies will help us understand the relationship between physical
function and social-isolation induced stress as well as define social isolation-induced neuromuscular decline as
a potential model to study age-related resiliency in older adults. Our results will have implications in older a...

## Key facts

- **NIH application ID:** 10057744
- **Project number:** 1R03AG067387-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** William David Arnold
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057744

## Citation

> US National Institutes of Health, RePORTER application 10057744, Social Isolation and Loss of Physical Function: Defining a Novel Neuromuscular Phenotype (1R03AG067387-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10057744. Licensed CC0.

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