UBIQUINOL-MEDIATED NRF2 ACTIVATION ENHANCES MITOCHONDRIAL FUNCTION AND ATTENUATES CELLULAR SENESCENCE

Aging is closely associated with mitochondrial dysfunction, oxidative stress, and impaired activation of the Nrf2 signaling pathway and all of these contribute to cellular senescence and subsequent cell death. Mitochondrial dysfunction in oxidative stress as well as Mitohormesis on the other hand, remains a paradoxical phenomenon in stress induced ageing and the role of cellular antioxidant like ubiquinol (CoQ10) remains least explored highlighting the need for more research. The present study investigated the cytoprotective properties of ubiquinol in UV-exposed L929 fibroblast cells, emphasizing its dual role in mitigating oxidative damage and enhancing mitochondrial function. Viability results depicted that lower concentrations of ubiquinol (6.25 and 12.5 μg/mL) effectively improved cell viability, reduced ROS levels, and significantly mitigated UV-induced DNA damage, as evidenced by comet assay results. Importantly, ubiquinol treatment enhanced Nrf2 translocation to the nucleus, activating the cell's endogenous antioxidant defense system and promoting cellular resilience attributing to cellular homeostasis. Additionally, ubiquinol mitigated mitochondrial membrane potential (MMP), preventing UV-induced mitochondrial depolarization, a hallmark of dysfunction. This protective effect against mitochondrial damage underscores ubiquinol’s role in maintaining mitochondrial homeostasis in stress induced condition. Moreover, a reduction in senescence-associated β-galactosidase staining was observed, indicating that ubiquinol effectively counteracted cellular senescence. These findings highlight the complex interplay between oxidative stress, mitochondrial function, and Nrf2 activation in aging and Ubiquinol’s ability to mitigate oxidative stress while simultaneously supporting mitochondrial bioenergetics and Nrf2-driven antioxidant responses positions it as a promising cytoprotective compound against UV-induced stress. The experimental results proposes that oxidative homeostasis is revisited in exogenous supplementation of ubiquinol at lower concentrations suggesting that while mild mitochondrial stress may promote longevity, ubiquinol's mitigation of mitochondrial function and oxidative balance could offer a complementary route to achieve cellular wellbeing.