Pancreatic β-cell aging in physiology and diabetes: emerging roles of m6A mRNA methylation

Pancreatic β-cells are essential for glucose homeostasis and are particularly vulnerable to age-related stress. Aging is a fundamental biological process characterized by the progressive functional decline of tissues and organs and defined by several interconnected hallmarks. In type 1 and type 2 diabetes, aging is accelerated - manifesting as DNA damage response, endoplasmic reticulum stress, and mitochondrial dysfunction, collectively driving β-cell dysfunction and senescence. N6-methyladenosine (m6A) is the most prevalent internal messenger RNA (mRNA) modification in eukaryotes. Emerging evidence demonstrates that m6A levels change with age in a tissue-specific manner, contributing to cellular dysfunction and age-related disease. In pancreatic β-cells, m6A hypomethylation compromises identity, survival, and function through mechanisms that include the IGF1 and insulin signaling pathways. Understanding how m6A methylation is regulated in aged β-cells may uncover new therapeutic strategies aimed at preserving β-cell functional mass and promoting healthy aging. This review focuses on pancreatic β-cell aging in physiological and diabetic conditions and examines the emerging role of m6A methylation in aging and diabetes progression.