# Skeletal muscle extracellular matrix remodeling through cyclic compressive loading in old rats recovering from disuse atrophy

> **NIH NIH F31** · UNIVERSITY OF KENTUCKY · 2021 · $7,509

## Abstract

PROJECT SUMMARY/ABSTRACT
The control of muscle mass is impaired in older adults, and is exacerbated by periods of muscle disuse
common to lengthy hospital stays, immobilization, and physical inactivity. The recovery following disuse
atrophy is incomplete in older adults, which contributes to functional decline. During the recovery of muscle
mass in older adults, there is an accumulation of intramuscular collagen, which contributes to functional
deficits. Lost strength following disuse atrophy in older adults is clinically important due to its tight correlation
with morbidity and loss of independence, which combined with the rising population of older adults, equates to
a large burden on the United States healthcare system. Therefore, it is critical therapies be made available to
regulate excessive collagen deposition in muscles from older adults. We propose massage in the form of cyclic
compressive loading may present as a useful alternative in regulating collagen deposition in muscles from
older adults, as it is a well-tolerated clinical tool. Using a rat model and our laboratory's custom-built robotic
massage device, we show massage is able to initiate the turnover of collagen in muscles of old rats
undergoing muscle regrowth. However, it is currently unclear how massage initiates collagen turnover or how
aging affects collagen regulation during the recovery of muscle mass in older adults. Therefore, the purpose of
this application is to (1) determine if massage impacts collagen remodeling by using isotope tracer methods
and mass spectroscopy and (2) identify how aging and massage impact the gene expression of collagen-
remodeling cell populations using single cell RNA sequencing. Results from the proposed experiments will
define the use of massage as a complementary health intervention for mitigating excessive collagen deposition
during the recovery period following disuse atrophy in older adults. Apart from assessing gaps in knowledge of
collagen regulation during muscle regrowth in old rats, this proposal is an excellent training platform to
accomplish my long-term career goals of becoming an independent scientist. The innovative research plan
prepared for this application is overseen by experts in the field of skeletal muscle aging, who have each
committed their time in training me to accomplish the goals set out in this application. Combining principles of
biomechanics and molecular biology, this is a unique training plan that not only benefits my training, but also
identifies massage as a complementary health intervention for older adults recovering from disuse atrophy.
The combination of innovative research, mentorship, and research environment each contribute towards
training to become an independent scientist in the field of skeletal muscle aging.

## Key facts

- **NIH application ID:** 10232953
- **Project number:** 1F31AT011472-01
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Zachary Hettinger
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $7,509
- **Award type:** 1
- **Project period:** 2021-04-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232953

## Citation

> US National Institutes of Health, RePORTER application 10232953, Skeletal muscle extracellular matrix remodeling through cyclic compressive loading in old rats recovering from disuse atrophy (1F31AT011472-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10232953. Licensed CC0.

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