Accepted_test

This thesis addresses the pressing need in gerontology for identifying compounds capable of modulating the number and activity of senescent cells. Berberine, known for its geroprotective qualities demonstrated across various models, is investigated for its potential association with antioxidant properties. The compound's ability to accumulate in the cytoplasm, mitochondria, and nucleus suggests multifaceted cellular interactions, including potential genotoxic stress induction leading to cell death, a mechanism exploited in anti-cancer therapy. Given the pivotal roles of mitochondrial dysfunction and oxidative stress in cellular senescence, the study explores two mitochondria-targeted derivatives of berberine: C10Berb and SkQBerb, with SkQBerb further enhanced with a plastoquinone molecule for augmented antioxidant properties.

The research, conducted on primary human skin fibroblasts, evaluates berberine and its derivatives for mitigating cisplatin-induced aging and erastin-induced cell death, a process linked to ferroptosis. Analysis reveals that both C10Berb and SkQBerb significantly reduce the senescence index at lower concentrations compared to berberine alone, indicating superior geroprotective effects. Additionally, the derivatives demonstrate enhanced efficacy in preventing erastin-induced fibroblast death, suggesting heightened antioxidant properties. These findings underscore the potential of modifying berberine to enhance its antioxidant and geroprotective capabilities, implicating oxidative stress in stress-induced cellular senescence. In conclusion, the study suggests the superiority of berberine derivatives, C10Berb and SkQberb, in conferring geroprotective effects compared to berberine alone.