Requirement of NAD and <i>SIR2</i> for Life-Span Extension by Calorie Restriction in <i>Saccharomyces cerevisiae</i>

TLDR

Calorie restriction extends lifespan across many species, yet the precise mechanism—whether it involves reduced reactive oxygen species—is still uncertain. The study sought to replicate calorie restriction in yeast through physiological or genetic interventions to evaluate its impact on lifespan. Researchers mimicked calorie restriction in yeast by applying physiological or genetic methods. The lifespan extension was absent in SIR2 or NPT1 mutants, indicating that calorie‑restriction‑induced longevity requires Sir2p activation by NAD.

Abstract

Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.