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 |
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Keywords
- Calorie restriction
- Longevity regulation
- Metabolic signaling
ASJC Scopus subject areas
- Genetics
- Developmental Biology
Cite this
Calorie restriction extends yeast life span by lowering the level of NADH. / Lin, Su Ju; Ford, Ethan; Haigis, Marcia; Liszt, Greg; Guarente, Leonard.
In: Genes and Development, Vol. 18, No. 1, 01.01.2004, p. 12-16.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Calorie restriction extends yeast life span by lowering the level of NADH
AU - Lin, Su Ju
AU - Ford, Ethan
AU - Haigis, Marcia
AU - Liszt, Greg
AU - Guarente, Leonard
PY - 2004/1/1
Y1 - 2004/1/1
N2 - 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.
AB - 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.
KW - Calorie restriction
KW - Longevity regulation
KW - Metabolic signaling
UR - http://www.scopus.com/inward/record.url?scp=0347128279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0347128279&partnerID=8YFLogxK
U2 - 10.1101/gad.1164804
DO - 10.1101/gad.1164804
M3 - Article
C2 - 14724176
AN - SCOPUS:0347128279
VL - 18
SP - 12
EP - 16
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 1
ER -