Peroxiredoxin 6: A Regulatory Target in Cellular Senescence and Age-Related Diseases

Significance: Oxidative stress is a key factor in inducing cellular senescence and age-related diseases. When the redox balance within the body is disrupted, sustained oxidative stress can lead to cellular senescence. The accumulation of senescent cells, in turn, triggers a variety of age-related diseases. Peroxiredoxin 6 (Prdx6) is a critical target in the intracellular regulation of redox homeostasis. Recent Advances: Prdx6 is a widely expressed antioxidant enzyme and the sole member of the peroxiredoxin family endowed with multiple enzymatic functions, including peroxidase activity along with acidic calcium-independent phospholipase A2 (aiPLA2) and lysophosphatidylcholine acyltransferase (LPCAT) activities. Its fundamental physiological functions involve protecting against oxidative stress and maintaining phospholipid homeostasis. Recent studies have shown that Prdx6 is widely involved in the regulation of cellular senescence and influences the development and progression of various age-related diseases. Critical Issues: Cellular senescence and age-related diseases, due to their complex mechanisms, lack effective treatments. Therefore, there is an urgent need to identify new therapeutic targets. This review discusses the biological characteristics of Prdx6 and its pathophysiological roles in cellular senescence and age-related diseases. Prdx6 may serve as a potential target for modulating cellular senescence and age-related diseases. Future Directions: The regulatory mechanisms of Prdx6 in age-related diseases warrant further investigation. Additionally, conducting drug screening to identify more molecules that can specifically target Prdx6 will provide new strategies for the treatment of age-related diseases. Antioxid. Redox Signal. 43, 400–426.