Graduation Year


Document Type

Master's Thesis


Master of Science


Biological Science

Program Director

Meredith Protas, PhD

First Reader

Pankaj Kapahi, PhD

Second Reader

Parminder Singh


Accumulation of advanced glycation end-products (AGEs) is linked to increased glycation stress which is associated with age-related deficits that ultimately affect the quality of life and longevity. Methylglyoxal (MGO), a highly reactive α-dicarbonyl (α-DC) produced as a by-product of glycolysis, plays a role in increasing levels of AGEs. This occurs when MGO undergoes insufficient detoxification by the glyoxalase system which becomes impaired with aging and diseases. As MGO accumulates, AGEs production is induced and results in heightened glycation stress, leading to more risk factors for disease. Our lab previously screened generally regarded as safe (GRAS) compounds and identified a cocktail of 5 compounds (designated Gly-low) that ameliorate the harmful effects of MGO toxicity. Gly-low treatment in mice enhances MGO detoxification, reduces body weight, promotes glucose homeostasis, and extends lifespan. Concurrently, another FDA-approved drug called rapamycin— known to inhibit mTOR (mechanistic target of rapamycin), which is responsible for cell growth and metabolism— has been proven to extend lifespan and protects aging muscle. In this study, we further explored the independent effects of Gly-low and rapamycin and determined if there was a synergistic effect between Gly-low and rapamycin in mice through a longitudinal study. We performed experiments at different time points, ranging from 18 months old to adulthood, to evaluate body composition (lean mass, bone density, and fat), muscle performance (endurance, muscle coordination and strength), glucose homeostasis, and survival. We also further determined the effects of MGO and its effects on 3T3-L1 cells in vitro. We explored the alteration of gene expression MGO could cause on pre-adipocytes, specifically looking at: Inflammation, cell cycle regulatory genes, and determined if differentiation is also affected through MGO treatment.

Available for download on Sunday, March 28, 2027