Carnosine Alleviates Oxidative Stress to Prevent Cellular Senescence by Regulating Nrf2/HO-1 Pathway: A Promising Anti-Aging Strategy for Oral Mucosa

Haoan He Chao Lv Yuhong Xie Wei Li Zihang Ling Bin Cheng ^* Xiaoan Tao ^*

• Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China

Aging is associated with significant metabolic alterations that contribute to cellular senescence and age-related functional decline in tissues. As individuals age, an increased prevalence of oral diseases and a gradual decline in oral function are observed. However, the metabolic shifts underlying oral mucosal aging remain unexplored. In this study, we performed a metabolomic analysis on mouse tongues across different age groups to identify carnosine as a potential biomarker of oral mucosal aging. Results showed significant differences among the young, adult, and old mouse groups, with amino acid metabolism being highlighted. Notably, the carnosine level decreased continuously with age. Consistent with these findings in metabolomics, carnosine synthase 1 (CARNS1) activity was inhibited, while carnosinase 2 (CNDP2) activity in-creased in the tongue mucosa of old mice compared with young and adult mice. Furthermore, carnosine protected oral epithelial cells from tBHP-induced cellular senescence through inhibiting oxidative stress and DNA damage, through regulating Nrf2/HO-1 pathway. Together, these findings suggest that carnosine has potential as an anti-aging agent for oral mucosa.