Graduation Year
2024
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Program Director
Meredith Protas, PhD
First Reader
Pankaj Kapahi, PhD
Second Reader
Kiyomi Kaneshiro, PhD
Abstract
Sarcopenia, the age-related degeneration of skeletal muscle, is linked to the buildup of glycotoxins, including advanced glycation end products (AGEs) and the reactive metabolite methylglyoxal (MGO), which exacerbate glycation stress and may worsen sarcopenia symptoms. Research has connected hyperglycemia, as seen in diabetes, with increased AGEs production, potentially linking it to sarcopenia. Our lab developed a cocktail of five compounds—nicotinamide, lipoic acid, thiamine, piperine, and pyridoxamine—and formulated them into the supplement Gly-Low, which we have found effectively reduces glycation stress linked to diabetes and Alzheimer's disease (Wimer et al., 2022). In this study, we evaluated Gly-Low's effectiveness in reducing glycation stress in aging mice, focusing on muscle quality and function. In aged wild-type mice, we administered three treatments: a Gly-Low diet to reduce glycation stress, MGO in water to elevate glycation stress, and a cotreatment of Gly-Low and MGO to evaluate Gly-Low's potential in counteracting MGO-induced stress. Following this treatment, we conducted various tests over a 5-month period to evaluate muscle function and integrity, including assessments of motor coordination, strength, balance, and neuromuscular function, using rotarod, grip strength, and wirehang tests. Additionally, locomotion, activity, and metabolism outcomes were analyzed through open field and metabolic cage assays. For aged mice, Gly-Low treatment consistently improved metabolic parameters such as body weight, food intake, body composition changes, and glucose regulation, regardless of MGO presence. Aged mice treated with MGO displayed age-related responses, while co-treatment with MGO and Gly-Low led to similar reductions in food intake and weight as Gly-Low alone, along with enhancements in muscle function, prompting further investigation. This study enhances our understanding of how manipulation of glycation stress impacts muscle function, providing insights into aging and age-related diseases.
Included in
Animals Commons, Animal Studies Commons, Biochemical Phenomena, Metabolism, and Nutrition Commons, Life Sciences Commons, Musculoskeletal Diseases Commons, Musculoskeletal, Neural, and Ocular Physiology Commons