Alpha-Glucosidase Inhibitors in Aging and Aging-Related Diseases: Clinical Applications and Relevant Mechanisms

Abstract

Aging is a complex and universal process marked by gradual functional declines at the cellular and tissue levels, often leading to a range of aging-related diseases such as diabetes, cardiovascular diseases, and cancer. Delaying the aging process can help prevent, slow down, and alleviate the severity of these various conditions, enhancing overall health and well-being. Alpha-glucosidase inhibitors (AGIs) are a class of widely used antidiabetic drugs that inhibit alpha-glucosidase in the small intestinal mucosa, delaying carbohydrate absorption and reducing postprandial hyperglycemia. Beyond their roles in diabetes treatment, AGIs have shown potential in extending lifespan and effectively treating aging-related diseases by modulating oxidative stress, gut microbiota, inflammatory responses, and nutrient-sensing pathways. This review summarizes recent advancements in the application of AGIs for preventing and treating aging and aging-related diseases, with a focus on their mechanisms and roles in these processes.

Figure 1.

Overview of AGIs. (A) Chemical structures of commercially available AGIs; (B) Listing timeline of AGIs; (C) Mechanisms of AGIs in controlling postprandial hyperglycemia. Abbreviations: AGIs, alpha-glucosidase inhibitors; FDA, U.S. Food and Drug Administration; GLP-1, glucagon-like peptide-1. Created with biorender.com.

Figure 2.

The effect of AGIs in the treatment of aging and aging-related diseases. AGIs play an important role in the treatment of aging and aging-related diseases such as diabetes mellitus, obesity, cardiovascular diseases, lung cancer, gastric cancer, hepatic cancer, colorectal cancer, and rheumatoid arthritis. Abbreviations: AGIs, alpha-glucosidase inhibitors; COPD, chronic obstructive pulmonary disease; MACE, major adverse cardiovascular events; BMI, body mass index; WC, waist circumstance. ↑, up; ↓, down. Created with biorender.com.

Figure 3.

Mechanisms of AGIs targeting aging and aging-related diseases. AGIs delay the aging process and provide protective effects against aging-related diseases achieved by modulating oxidative stress, gut microbiota, inflammation response, and nutrient sensing. Abbreviations: AGIs, alpha-glucosidase inhibitors; GLP-1, glucagon-like peptide-1; IGF-1, insulin/insulin-like growth factor 1 receptor; MCP-1, chemoattractant protein-1; SCFAs, short-chain fatty acids. ↑, improved or up; ↓, attenuated or down. Created with biorender.com.