Role of Advanced Glycation End Products and Mitohormesis in Cancer Development and Progression

Abstract

Advanced glycation end products (AGEs) are molecules formed via non-enzymatic reactions between reactive dicarbonyls and macromolecules, including proteins, lipids, or DNA. Mitochondria sense and integrate stress signals and induce changes in cellular function by regulating metabolism, redox balance, and proteostasis to maintain homeostasis, a process known as mitohormesis. Dysregulation of cellular metabolism and redox imbalance are the major driving forces behind the increased production of intracellular reactive dicarbonyls and AGEs. Although the association between increased reactive dicarbonyl levels and cancer development has been investigated, its causal relationship remains controversial. This review integrates recent evidence on the association between increased levels of reactive dicarbonyls and mitochondrial dysfunction and provides mechanistic insights into carcinogenesis associated with AGE-mediated disruption of mitohormesis.