title: Calorie restriction extends yeast life span by lowering the level of NADH.
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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. slin@ucdavis.edu
authors.forename: Su-Ju
authors.initials: SJ
authors.lastname: Lin
authors.forename: Ethan
authors.initials: E
authors.lastname: Ford
authors.forename: Marcia
authors.initials: M
authors.lastname: Haigis
authors.forename: Greg
authors.initials: G
authors.lastname: Liszt
authors.forename: Leonard
authors.initials: L
authors.lastname: Guarente
mesh_terms: D003470:Culture Media; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000254:growth & development*; D037761:Sirtuins / Q000378:metabolism
chemical_list: D003470:Culture Media; D009243:NAD; D037761:Sirtuins