Buck Institute for Research on Aging

Investigating the Interplay Among Cellular Senescence, Insulin Resistance, and Glycation Stress

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Aging is a natural process marked by the gradual decline in the functional abilities of living organisms. This process involves various hallmarks, with two critical ones being cellular senescence and insulin resistance, both of which contribute to age-related diseases. Cellular senescence refers to a state where cells lose their ability to divide and release certain molecules, impacting various health conditions. Insulin resistance, on the other hand, is closely linked to the development of type 2 diabetes and neurodegenerative disorders. Although these hallmarks coexist in multiple conditions, how they interact with each other is still unknown. A key factor in this scenario could be Methylglyoxal (MGO), a byproduct of glucose metabolism, which can chemically modify proteins through a process called glycation, leading to the formation of advanced glycation end products (AGEs). AGE levels are known to increase in conditions like diabetes, menopause, and cancer. Importantly, as we age or experience health issues, our body’s natural defense systems, known as glyoxalase systems, become less effective in combating glycation stress. Our research focuses on understanding how MGO-induced glycation stress influences insulin resistance and cellular senescence. We are particularly interested in studying its effects on pancreatic β-cells and adipose tissue, two areas closely related to metabolic and aging processes. By investigating the interplay between MGO-induced protein glycation, insulin resistance, and cellular senescence, our goal is to develop potential therapeutic interventions that could mitigate the effects of aging and age-related diseases, ultimately aiming to enhance the well-being of older individuals and reduce the societal burden of such conditions.