Investigation of the protective effects of Bcl-2 and Bcl-xL proteins against age-dependent oxidative stress in a yeast model

Aging, which occurs as a result of accumulated damage at the molecular, cellular, and tissue levels due to the influence of genetic and environmental factors, has become one of the most extensively studied phenomena due to its complex nature. Although yeast aging shares certain similarities with higher eukaryotic systems, its simple and well-characterized genetic structure provides significant advantages in elucidating aging mechanisms. In this study, the protective effects of human anti-apoptotic Bcl-2 and Bcl-xL proteins on oxidative stress and aging were investigated in detail using the Saccharomyces cerevisiae yeast model. The findings indicate that both proteins significantly reduced oxidative damage and exhibited anti-aging effects by enhancing reproductive survival capacity. These effects were mediated through the dynamic interaction of components exhibiting both pro- and antioxidant activities at different stages of lifespan. Additionally, both Bcl-2 and Bcl-xL proteins partially prevented age-related cellular damage and morphological deformations. Notably, Bcl-xL expressing yeast cells reached maximum levels of key antioxidant enzyme activities and total antioxidant content on the 8th day of their lifespan, thereby providing significant protection during the later stages of aging. The results obtained from the chemometric data analysis, which utilized IR spectra, showed consistency with the findings from both the biochemical and morphological analyses. In this context, understanding the impact of Bcl-xL on cellular redox balance in yeast cells could provide insights into its indirect antioxidant mechanisms in higher eukaryotes. Consequently, the roles of Bcl-2 and Bcl-xL in combating aging and oxidative stress offer a new perspective for identifying potential therapeutic targets.