Chronological and replicative life-span extension in Saccharomyces cerevisiae by increased dosage of alcohol dehydrogenase 1.

Alcohol dehydrogenase 1 (Adh1)p catalyses the conversion of acetaldehyde to ethanol, regenerating NAD+. In Saccharomyces cerevisiae, Adh1p is oxidatively modified during ageing and, consequently, its activity becomes reduced. To analyse whether maintaining this activity is advantageous for the cell, a yeast strain with an extra copy of the ADH1 gene (2xADH1) was constructed, and the effects on chronological and replicative ageing were analysed. The strain showed increased survival in stationary phase (chronological ageing) due to induction of antioxidant enzymes such as catalase and superoxide dismutases. In addition, 2xADH1 cells displayed an increased activity of silent information regulator 2 (Sir2)p, an NAD+-dependent histone deacetylase, due to a higher NAD+/NADH ratio. As a consequence, a 30% extension in replicative life span was observed. Taken together, these results suggest that the maintenance of enzymes that participate in NAD+/NADH balancing is important to chronological and replicative life-span parameters.