An open access paper in which researchers delve into the mechanisms of longevity induced through calorie restriction in yeast: "Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. ... . Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan. ... CR-induced NO production may extend lifespan by increasing the stress response (mitohormesis). Our study may have uncovered potential novel components in the CR pathway and provided tools to analyze the interconnections between NO, mitochondrial respiration, CR, and longevity. Although the CR mimics identified in this study share similar NO levels, lifespan, and oxygen consumption phenotypes with CR, they may activate NO production and regulate mitochondrial respiration and lifespan via different mechanisms. It will be enlightening to examine these differences in future studies. Finally, we propose that CR likely confers its beneficial effects via a mitochondria-NO-mediated adaptive metabolic shift, which optimizes metabolism and at the same time improves cellular defense system against the oxidative stress that accumulates with age."