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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 12-16 |
| Number of pages | 5 |
| Journal | Genes and Development |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2004 |
Keywords
- Calorie restriction
- Longevity regulation
- Metabolic signaling
ASJC Scopus subject areas
- Genetics
- Developmental Biology
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Lin, S. J., Ford, E., Haigis, M., Liszt, G., & Guarente, L. (2004). Calorie restriction extends yeast life span by lowering the level of NADH. Genes and Development, 18(1), 12-16. https://doi.org/10.1101/gad.1164804