Author ORCID Identifier

Date Available


Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation


Health Sciences


Rehabilitation Sciences

First Advisor

Dr. Esther E. Dupont-Versteegden

Second Advisor

Dr. Timothy A. Butterfield


The combination of age and disuse-related skeletal muscle atrophy predisposes older adults to reduced mobility, loss of independence, and poor quality of life. Poor health outcomes resulting from periods of disuse in older adults are exacerbated by an inability to fully recover, ultimately accelerating geriatric populations towards further functional decline. Aged-related changes to skeletal muscle viscoelastic properties, specifically of muscle extracellular matrix (ECM) stiffness, may not only impact how muscle responds during recovery, but also to interventions intended to augment recovery. Remodeling of muscle ECM in the aged may therefore benefit muscle mass recovery, yet therapies focused on ECM remodeling in aged muscle recovering from disuse are currently lacking. Here we report that muscle stiffness is a significant contributor to how aged muscle responds to mechanical loads, as high loads of cyclic compression preferentially damage aged (30 month) but not adult rat (10 month) gastrocnemius muscle recovering form disuse atrophy. We show that lower loads of cyclic compression serve as a mechanotherapy for skeletal muscle ECM remodeling in aged rats recovering from disuse, in part by reprogramming the cellular transcriptomes of fibro-adipo progenitor cells (FAPs) and macrophages. Lastly, we provide evidence for an age-related impairment to skeletal muscle immune cell activation during the recovery from disuse atrophy, potentially contributing to the impaired recovery of muscle size in the aged. The data presented in these studies demonstrates the dynamic and influential role non-myogenic cells play during the recovery from disuse atrophy, which are strongly influenced by age and can be targeted using mechanotherapy to enhance ECM remodeling.

Digital Object Identifier (DOI)

Funding Information

This study was supported by the University of Kentucky's Center for Clinical and Translational Science TL1 Pre-doctoral Training Program in 2019-2020 (no.: UL1TR001998), and the National Institutes of Health's National Center for Complementary and Integrative Health Pre-doctoral National Research Service Award in 2021 (no.: 1F31AT011472-01).

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