Active Immunization against Myostatin and Activin A: A Therapeutic Strategy for Sarcopenia

Author

• Mishfak Abdullah Mohamed Mansoor, University of Central FloridaFollow

Keywords

Sarcopenia, Muscle Atrophy, Aging, Myostatin, Activin A, Growth Hormone

Abstract

Muscle wasting is a significant hurdle in patients due to immobilization, prolonged bed rest, injury or biological aging. In particular, the older population develops sarcopenia, characterized by progressive loss of muscle strength due to natural aging. However, there are no FDA-approved drugs for sarcopenia, and it is critical to explore novel therapeutics. Here, we explore an active immunization strategy to suppress the activity of negative regulators of muscle growth, namely myostatin and activin A. We used a growth hormone (GH)-deficient murine model to investigate whether immunization with myostatin and activin A improves muscle strength through remodeling of the muscle tissue, independent of GH/IGF-1 associated muscle mass changes. We showed that immunization increases lean mass and improves strength in animals with normal GH production. Importantly, in GH-deficient animals, long-term inhibition of myostatin and activin A improved strength despite the lack of GH-associated muscle mass gain. We also report that with GH-deficiency, myostatin inhibition modulates transcriptomic shift in the gastrocnemius muscle, allowing remodeling of the skeletal muscle and an increase in energy expense without any changes in muscle growth. Increased grip strength was also observed in an aged murine model subjected to the same immunization schedule. We also observed changes in lipid levels in gastrocnemius tissue, further emphasizing that this inhibition strategy alters skeletal muscle contractility by remodeling tissue constituents, thereby enabling enhanced performance. Together, we report that long-term inhibition of myostatin and activin A via active immunization enhances skeletal muscle performance through tissue remodeling, independently of GH-associated lean mass gain. In addition, circulating miRNAs was profiled in response to PD-1 blockade therapy for lung cancer, as lung cancer patients suffer from sarcopenia and a risk factor, and it is critical that common biomarkers between the two diseases are explored to bridge the gap that could lead to improved therapeutics.

Completion Date

2025

Semester

Fall

Committee Chair

Masternak, Michal

Degree

Doctor of Philosophy (Ph.D.)

College

College of Medicine

Department

Biomedical Sciences

Format

PDF

Release Date

12-15-2026

Document Type

Dissertation

Campus Location

College of Medicine

Subjects

Muscles--Aging; Geriatrics--Immunological aspects; Muscle strength--Research; Muscles--Diseases--Research; Growth factors--Therapeutic use

STARS Citation

Mohamed Mansoor, Mishfak Abdullah, "Active Immunization against Myostatin and Activin A: A Therapeutic Strategy for Sarcopenia" (2025). Graduate Thesis and Dissertation post-2024. 538.
https://stars.library.ucf.edu/etd2024/538