Nuclear Receptor Nur77: A Key Factor and Potential Therapeutic Target in the Aging Regulatory Network

Aging is a complex process marked by the gradual functional decline of an organism. It involves imbalances in cellular homeostasis and decreased organ regenerative capacity, causing a significant increase in chronic diseases and mortality. Aging involves a cascade of molecular events such as genomic instability, epigenetic remodeling, and metabolic dysfunction. Targeting key molecular nodes can effectively delay aging and age-related disease progression. Nur77, an NR4A nuclear receptor, is key to stress response, energy sensing, and inflammation regulation. This molecule assists in maintaining stem cell homeostasis, repairing mitochondrial dysfunction, and regulating autophagy and protein quality control, which are core aging events. However, a systematic analysis of the regulatory roles and synergistic effects of Nur77 within the aging network remains lacking. This review comprehensively describes the structure and function of Nur77, explores its role in age-related mechanisms and diseases, and discusses its potential as a diagnostic and therapeutic target. These insights support the development of novel anti-aging strategies based on the Nur77 signaling pathway.