The study shows that the tiny protein humanin helps eye‑lens cells survive oxidative stress, which is a key factor in age‑related cataracts. When cells were stressed, they made more humanin, and giving extra humanin lowered harmful reactive oxygen species, protected mitochondria, and boosted the cell’s cleanup system. If humanin is blocked, these benefits disappear, indicating its direct protective role.

Oxidative stress-induced injury and apoptosis of human lens epithelial cells (HLECs) are early events in the development of age‑related cataracts (ARCs). Humanin (HN) is a mitochondrial‑related peptide that serves a cytoprotective role in various cell types and animal models. Following HN knockdown or overexpression, the level of reactive oxygen species (ROS), mitochondrial membrane potential and mitochondrial DNA copy number, cell viability, LDH activity and apoptosis of HLECs under oxidative stress were detected, and apoptosis and autophagy were detected via transmission electron microscopy. The results suggested that HN may be involved in the response of HLECs to oxidative stress, and that HN expression was significantly upregulated under oxidative stress conditions. Furthermore, exogenous HN reduced intracellular ROS content and mitochondrial damage, and enhanced mitochondrial biosynthesis; however, this protection was lost in an endogenous HN knockdown cell model. In addition, to the best of our knowledge, the present study was the first to identify that HN increased mitochondrial autophagy, which was involved in reducing ROS production under oxidative stress. The present study indicated a potential mechanism underlying the anti‑oxidative damage and apoptotic effects of HN under oxidative stress. In conclusion, HN may be a potential therapeutic target for ARCs as it has a significant cellular protective effect on HLECs under oxidative stress; therefore, further study is required to investigate its role in the occurrence and development of ARCs.