Green Alga <i>Enteromorpha prolifera</i> Oligosaccharide Exerts Antiaging Effects through Targeted Modulation of Protein <i>O-</i> GlcNAcylation

Aging and diabetes are intricately linked, with metabolic dysregulation playing a pivotal role in the pathophysiology of both conditions. This study investigates the therapeutic potential of <i>Enteromorpha prolifera</i> oligosaccharide (EPO) in mitigating aging-related metabolic decline through modulation of O-GlcNAcylation. The results demonstrate that EPO treatment significantly reduced O-GlcNAc levels, thereby attenuating ROS accumulation and alleviating cell cycle arrest to counteract aging-associated metabolic decline. Specifically, shOGA increased ROS by 77.0% and induced G2/M arrest (12.2%). These alterations were mimicked by TMG but reversed by EPO, identifying OGA as the primary driver of ROS generation and cell cycle regulation. shHCF1 decreased ROS (48.8% to 28.3%), G0/G1 (59.7%), and S phase (6.6%) but increased G2/M to 30.9%, suggesting ROS attenuation alongside G2/M arrest. Overall, this research highlights the role of EPO in regulating key cellular processes, providing new insights for the development of antiaging therapies.