Research Project Highlights
Mitochondria are essential for cellular energetics and homeostasis, including ATP production, reactive oxygen species (ROS), other key metabolic processes including apoptosis and calcium regulation. The consumption of oxygen by the mitochondrial electron transport chain leads to production of ATP but also to release of electrons that can lead to the generation of free radical species and oxidative damage. Thus, proper function and control of mitochondria is critical. Mitochondrial function has been well documented to be compromised with aging leading to altered physiologic function and age-associated diseases. Our and others’ work on sarcopenia and chronic diseases suggest that altered mitochondrial function and increased generation of reactive oxygen species contribute to the physiologic decline seen in sarcopenia and age-associated diseases. Within our laboratory and in collaboration with others, our lab investigates the role of mitochondrial defects on muscle and other organ dysfunction with age and diseases.
Mitochondrial bioenergetics, byproduct (free radicals), and calcium regulations are key features critical for cellular homeostasis.
Oxidative stress and neuromuscular junction (NMJ) disruption play a key role in the progression of age-associated muscle loss and weakness (i.e. sarcopenia) and chronic diseases that result in muscle weakness and atrophy, including cancer cachexia. Mitochondria is primary site of free radical generation in muscle. However, its role in NMJ disruption and neurogenic atrophy yet to be investigated. My lab uses several transgenic and knockout animal models with modified antioxidant defense systems (specific to the mitochondria, i.e. super oxide dismutase2 and peroxiredoxin3) to ask whether changes in redox balance delay or accelerate NMJ disruption and neurogenic atrophy with age. Our goal is to uncover key pathways involved in sarcopenia with the hope that we can provide new information that can be used to design effective interventions to delay or diminish muscle loss and weakness in the elderly.
Proteins in neuromuscular junction in mouse skeletal muscle. Acetylcholine receptor is pseudo-colored in green, while motor neuron is pseudo-colored in red. Yellow represents innervation.
Despite the clinical significance in quality of life in the elderly and cancer patients, no effective pharmacological therapies are currently available to mitigate muscle atrophy and weakness. The goal of my lab is to test the ability of a novel and promising pharmacological intervention unacylated ghrelin to delay skeletal muscle weakness and loss of muscle mass with aging (i.e. sarcopenia) and in cancer cachexia. Circulating ghrelin is reduced in the elderly, but it has direct impacts on muscle growth and contractile function. We and others have shown unacylated ghrelin promotes protein synthesis while downregulating proteolytic pathways in acute disease models and redox-dependent sarcopenia. In parallel studies, my lab is also investigating the effect of unacylated ghrelin in cancer cachexia. If unacylated ghrelin offers protection in animals, it will be an excellent candidate for clinical trials because it has an excellent safety profile in humans and no effect on cancer cell growth. The goal of the project is to extend health span in the elderly and diseases.
A. 28 amino acid structure of unacylated ghrelin. B. Animals treated with unacylated ghrelin have increased muscle mass and contractile function in an animal model of accelerated sarcopenia, Sod1KO (Ahn et al., Antioxidants, 2023).
|Bumsoo Ahn, PhD
|Eunyoung Kim, PhD
|Ryan Pettit-Mee, PhD
Undergraduate research intern
View the most recent highlighted research articles, book chapters, and publications from the Ahn lab at Wake Forest University School of Medicine.