Calorie restriction extends yeast life span by lowering the level of NADH.
By Su-Ju Lin, E. Ford, M. Haigis, G. Liszt, L. Guarente. Genes & Development, 2004
675 citations recorded by the source corpus.
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.
Subfields: Aging, Geriatrics and Gerontology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/87af52902bef6f7a1cf59f72f00a9850afe2d8d8
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Citations in the corpus
- Sirt1 Regulates Insulin Secretion by Repressing UCP2 in Pancreatic β Cells (2005, positive): “A decrease in the NAD/NADH ratio has also been shown to down-regulate Sir2 activity in other physiological contexts [15,21,50].”
- Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, positive): “Recently, however, it has become clear that a steady decline in total NAD levels over time is a natural part of life for all species, from yeast to humans (Balan et al., 2008; Belenky et al., 2007; Lin et al., 2004; Massudi et al., 2012; Mouchiroud et al., 2013; Zhang et al., 2016; Zhu et al., 2015)”
- NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences (2008, neutral): “span of yeast by decreasing NADH levels (173).”
- SIRT1 and other sirtuins in Metabolism (2013, background): “SIRT1 activity can be regulated post-transcriptionally by several mechanisms, including phosphorylation [107,108], interactions with other proteins such as DBC1 [109,110], or changes in NAD+ levels [111].”
- Calorie restriction, SIRT1 and metabolism: understanding longevity (2005, methodology): “The link between respiration changes and Sir2 activity is thought to be an alteration in the NAD/NADH ratio, as was suggested by one grou”
- NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “However, deacetylation is not the singular function of all sirtuins, as SIRT4 can act as a lipoamidase (Mathias et al., 2014) and, along with SIRT6, as an NAD+-dependent mono-ADP-ribosyltransferase (Haigis et al., 2006; Liszt et al., 2005).”
- Sirtuins in aging and age-related disease. (2006, background): “, 2002), reduced NADH levels (Lin et al., 2004), and/or reduced nicotinamide levels (Anderson et al.”
- Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ (2004, methodology): “We do not yet know whether Sirt1 is activated upon fasting by a change in the NAD/NADH ratio, as has been proposed in yeas”
- A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine (2005, background): “and thus increasing expression of the antioxidant and stress response genes (119, 120).”