Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.

@article{Lin2000RequirementON,
  title={Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.},
  author={S. J. Lin and Pierre-Antoine Defossez and Leonard P Guarente},
  journal={Science},
  year={2000},
  volume={289 5487},
  pages={
          2126-8
        }
}
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… 

Sir2-Independent Life Span Extension by Calorie Restriction in Yeast

It is found that combining calorie restriction with either of these genetic interventions dramatically enhances longevity, resulting in the longest-lived yeast strain reported thus far and indicates that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes.

HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction

It is shown that Sir2-independent life-span extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive ribosomal DNA, the same mechanism by which Sir2 extends life span.

Yeast Life-Span Extension by Calorie Restriction Is Independent of NAD Fluctuation

It is reported that CR reduces nuclear NAD+ levels in vivo, and this data implicate alternate mechanisms of Sir2 regulation by CR that are not affected by physiological alterations in the NAD+:NADH ratio.

Calorie restriction extends yeast life span by lowering the level of NADH.

It is shown that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2, validating the model that NADh regulates yeast longevity in response to CR.

Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast

It is demonstrated that respiration is not required for the longevity benefits of CR in yeast, and shows that nicotinamide inhibits life span extension by CR through a Sir2-independent mechanism, and suggests that CR acts through a conserved, Sir2 -independent mechanism in both PSY316 and BY4742.

Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients

It is proposed that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast.

High Osmolarity Extends Life Span in Saccharomyces cerevisiae by a Mechanism Related to Calorie Restriction

Genetic and microarray analysis indicates that high osmolarity extends the life span by activating Hog1p, leading to an increase in the biosynthesis of glycerol from glycolytic intermediates, thereby activating Sir2p and promoting longevity.

Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae

It is concluded that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

Sir2 mediates longevity in the fly through a pathway related to calorie restriction.

  • B. RoginaS. Helfand
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
It is demonstrated that an increase in Drosophila Sir2 (dSir2) extends life span, whereas a decrease in dSir2 blocks the life-span-extending effect of calorie reduction or rpd3 mutations, which leads to a genetic pathway by which calorie restriction extends life spans and provides a framework for genetic and pharmacological studies of life span extension in metazoans.

Sir2 Blocks Extreme Life-Span Extension

...

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