Roles of microRNA in aging and dietary restriction-induced longevity

Abstract

Aging is a multifactorial biological process driven by the progressive decline of cellular and tissue homeostasis. Increasing evidence has identified microRNAs (miRNAs) as key epigenetic regulators that fine-tune gene expression networks involved in aging and lifespan determination. Across model organisms—including Caenorhabditis elegans, Drosophila melanogaster, and mammals—numerous miRNAs exhibit age-dependent expression patterns and modulate longevity by targeting conserved signaling pathways such as insulin/IGF-1 signaling, mTOR, autophagy, mitochondrial homeostasis, and inflammatory responses. These small non-coding RNAs function as network regulators that coordinate multiple biological processes underlying organismal aging. In addition to regulating intrinsic aging pathways, miRNAs have emerged as important mediators of environmental longevity interventions. Moreover, dietary restriction (DR), one of the most robust and evolutionarily conserved lifespan-extending interventions, reshapes miRNA expression programs that control metabolic adaptation, stress resistance, and nutrient-sensing pathways. Furthermore, accumulating evidence indicates that circulating miRNAs detected in body fluids—including blood, serum, and urine—may serve as minimally invasive biomarkers for biological aging and age-related diseases. In this review, we summarize current insights into the roles of miRNAs in lifespan regulation across model organisms, discuss their involvement in DR-mediated longevity, and highlight their emerging applications as diagnostic biomarkers and potential therapeutic targets. Finally, we discuss future directions emphasizing integrative multi-miRNA regulatory networks and miRNA-based aging clocks, which may provide new opportunities for understanding aging mechanisms and developing strategies to promote healthy longevity.