Growth phase-dependent roles of Sir2 in oxidative stress resistance and chronological lifespan in yeast.

Silent Information Regulator 2 (Sir2), a conserved NAD(+)-dependent histone deacetylase, has been implicated as one of the key factors in regulating stress response and longevity. Here, we report that the role of Sir2 in oxidative stress resistance and chronological lifespan is dependent on growth phase in yeast. In exponential phase, sir2Δ cells were more resistant to H2O2 stress and had a longer chronological lifespan than wild type. By contrast, in post-diauxic phase, sir2Δ cells were less resistant to H2O2 stress and had a shorter chronological lifespan than wild type cells. Similarly, the expression of antioxidant genes, which are essential to cope with oxidative stress, was regulated by Sir2 in a growth phase-dependent manner. Collectively, our findings highlight the importance of the metabolic state of the cell in determining whether Sir2 can protect against or accelerate cellular aging of yeast.