title: Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.
abstract: In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.
authors: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors: Szu-Chieh
authors: SC
authors: Mei
authors: Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
authors: Charles
authors: C
authors: Brenner
mesh_terms: D031204:Caloric Restriction; D017077:Culture Media, Conditioned; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D050296:Microbial Viability; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000502:physiology; D056565:Sirtuin 2 / Q000502:physiology
chemical_list: D017077:Culture Media, Conditioned; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D005947:Glucose
references: Genes Dev. 2003 Feb 1;17(3):313-21
references: 12569120
references: J Biol Chem. 2002 May 24;277(21):18881-90
references: 11884393
references: J Biol Chem. 2009 Jun 19;284(25):17110-9
references: 19416965
references: Cell. 2007 May 4;129(3):473-84
references: 17482543
references: PLoS Genet. 2005 Nov;1(5):e69
references: 16311627
references: F1000Res. 2013 Oct 15;2:216
references: 24555104
references: Nature. 2003 May 8;423(6936):181-5
references: 12736687
references: Science. 2005 Nov 18;310(5751):1193-6
references: 16293764
references: PLoS One. 2011;6(5):e19710
references: 21589930
references: Trends Genet. 2007 Feb;23(2):74-80
references: 17207887
references: Nature. 2012 Dec 13;492(7428):261-5
references: 23172144
references: Aging Cell. 2012 Aug;11(4):599-606
references: 22498653
references: Nature. 2012 Sep 13;489(7415):318-21
references: 22932268
references: Nature. 1959 Jun 20;183(4677):1751-2
references: 13666896
references: Science. 2003 Dec 19;302(5653):2124-6
references: 14605207
references: BMC Chem Biol. 2010 Feb 22;10:2
references: 20175898
references: Nat Rev Genet. 2005 Nov;6(11):866-72
references: 16304601
references: Exp Gerontol. 2001 Dec;37(1):27-31
references: 11738144
references: Science. 2000 Sep 22;289(5487):2126-8
references: 11000115
references: Nature. 2009 Jun 11;459(7248):802-7
references: 19516333
references: Science. 2010 Apr 16;328(5976):321-6
references: 20395504
references: Genes Dev. 2004 Jan 1;18(1):12-6
references: 14724176
references: Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11727-31
references: 25071164
references: J Vis Exp. 2009;(28). pii: 1209. doi: 10.3791/1209
references: 19556967
references: Aging Cell. 2003 Apr;2(2):73-81
references: 12882320
references: Science. 2009 Jul 10;325(5937):201-4
references: 19590001
references: Comput Struct Biotechnol J. 2013 May 27;4:e201301012
references: 24688693
references: Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4916-20
references: 22421136
references: PLoS Biol. 2004 Sep;2(9):E296
references: 15328540
references: PLoS One. 2014;9(9):e106496
references: 25188219