Calorie restriction extends yeast life span by lowering the level of NADH
TL;DR: 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.
read more
Abstract: Calorie restriction (CR) extends life span in a wide variety of species. Previously, we showed that calorie restriction increases the replicative life span in yeast by activating Sir2, a highly conserved NAD-dependent deacetylase. Here we test whether CR activates Sir2 by increasing the NAD/NADH ratio or by regulating the level of nicotinamide, a known inhibitor of Sir2. We show that CR decreases NADH levels, and that NADH is a competitive inhibitor of Sir2. A genetic intervention that specifically decreases NADH levels increases life span, validating the model that NADH regulates yeast longevity in response to CR.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Sir2-Independent Life Span Extension by Calorie Restriction in Yeast
TL;DR: 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.
The effects of temperature and diet on age grading and population age structure determination in Drosophila.
Wen C. Aw,J. William O. Ballard +1 more
TL;DR: The results strongly suggest that appropriate calibration models need to be developed in the laboratory before the non-invasive, inexpensive and high throughput near-infrared spectroscopy technique to determine the age of Drosophila flies can be reliably used in field.
Additional file 2 of NADH elevation during chronic hypoxia leads to VHL-mediated HIF-1α degradation via SIRT1 inhibition
Joo Hyun Yoo,Kim Mi Yeon,Woo Seon-Rang,Jeong， Jae Min,Kim Yong Min,Kim Joon,Yun Mi-Yong,Shin Hyun Jin,Lee Kee Ho +8 more
- 14 Aug 2024
Abstract: Supplementary Material 2
The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions.
Marta P. Silvestre,Marta P. Silvestre,Benoit Viollet,Paul W. Caton,J. Leclerc,Iori Sakakibara,Marc Foretz,M.C. Holness,Mary C. Sugden +8 more
TL;DR: It is demonstrated that skeletal muscle-specific AMPK deficiency impairs the beneficial effects of CR on glucose tolerance and that these effects may be dependent on reduced SIRT1 levels.
Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex
Qinghong Zhang,Su Yan Wang,Capucine Fleuriel,Dominique Leprince,Jonathan V. Rocheleau,David W. Piston,Richard H. Goodman +6 more
TL;DR: It is proposed that the reduction in transcriptional repression mediated by HIC1, due to the decrease of CtBP binding, increases SIRT1 expression, which allows the specific regulation of Sirt1 in response to nutrient deprivation.
References
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.
3.6K
Guide to yeast genetics and molecular biology
Christine Guthrie,Gerald R. Fink +1 more
TL;DR: This volume and its companion, Volume 350, are specifically designed to meet the needs of graduate students and postdoctoral students as well as researchers, by providing all the up-to-date methods necessary to study genes in yeast.
2.6K
The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
TL;DR: It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
TL;DR: In this paper, the lifespan of C. elegans strains containing duplications of chromosomal regions was surveyed and it was shown that a duplication containing sir-2.1-the SIR2 gene most homologous to yeast-confers a lifespan that is extended by up to 50%.
2K
Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae
TL;DR: These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.
1.9K