Accepted_test

This study addresses the critical need for identifying geroprotective agents, particularly within cell cultures, in gerontological research. Given the significant role of mitochondrial dysfunction in age-related pathologies, activation of mitophagy, crucial for long-lived cells like neurons and myocytes, emerges as a potential therapeutic way. The 7-hydroxycoumarin derivative UB3-C10, known for its robust uncoupling properties and low toxicity, including neuronal cells, is investigated for its geroprotective potential in the model of chronological aging of human muscle cells.

The research, conducted on immortalized MB135 myoblasts, examines the effects of UB3-C10 on cell senescence, inflammatory cytokine secretion, and mitochondrial dynamics. Results indicate that UB3-C10, particularly at a concentration of 50 μM, reduces the proportion of senescent cells and levels of p21 protein while increasing phosphorylated pRb (Ser807/811), suggesting geroprotective properties. Notably, UB3-C10 does not affect pro-inflammatory cytokine secretion. Mitochondrial dynamics assessment reveals a dose-dependent decrease in mitochondrial content after 24 hours of UB3-C10 treatment, with levels returning to baseline after 72 hours, indicative of induced mitophagy. Fluorescence microscopy further confirms mitophagy induction by UB3-C10, although the precise mechanisms remain to be elucidated.

In conclusion, UB3-C10 demonstrates geroprotective effects in the model of chronological aging of human muscle cells, potentially mediated through its impact on mitochondrial dynamics. These findings underscore the therapeutic potential of UB3-C10 in mitigating age-related cellular senescence, highlighting the importance of further investigations into its mechanisms of action.