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Correspondence IncreasedLifeSpanduetoCalorie RestrictioninRespiratory-Deficient Yeast thinkitislikelythatdifferencesinpathwaysidenti?edby Kaeberleinetal.simplyre?ecttheirdifferentexperimental protocolsanddonotnegateourearlier?ndingsand interpretations.Futhermore,thefactthattheychangedthe conditionsweemployedasCRandomittedrelevantdata havecreatedconfusion. “ Su-JuLin,LeonardGuarente TheKaeberleinetal.paperintheNovember2005issueof PLoSGenetics[1]claimedthatcalorierestriction(CR)inyeast doesnotrequirerespirationtoextendlifespanofmother cells.Thisclaimchallengesourearlier?ndingthatdeleting CYT1(encodingcytochromec1)preventedCR-associated longevity[2]. However,thereisafundamentaldifferenceinthetwo experiments:theseauthorstypicallyuse0.05%glucoseas theirCRmediainsteadofthe0.5%glucoseinour Su-JuLin UniversityofCaliforniaDavis Davis,California,UnitedStatesofAmerica LeonardGuarente(leng@) MassachusettsInstituteofTechnology Cambridge,Massachusetts,UnitedStatesofAmerica References 1. 2. 3. 4. 5. KaeberleinM,HuD,KerrEO,TsuchiyaM,WestmanEA,etal.(2005) Increasedlifespanduetocalorierestrictioninrespiratory-de?cientyeast. PLoSGenet1:DOI:10.1371/journal.pgen.0010069 LinSJ,KaeberleinM,AndalisAA,SturtzLA,DefossezPA,etal.(2002) CalorierestrictionextendsSaccharomycescerevisiaelifespanbyincreasing respiration.Nature418:344–348. BrauerMJ,SaldanhaAJ,DolinskiK,BotsteinD(2005)Homeostatic adjustmentandmetabolicremodelinginglucose-limitedyeastcultures. MolBiolCell16:2503–2517. KaeberleinM,AndalisAA,FinkGR,GuarenteL(2002)Highosmolarity extendslifespaninSaccharomycescerevisiaebyamechanismrelatedto calorierestriction.MolCellBiol22:8056–8066. experiments(comparedwith2%glucoseincontrols).Attheir verylowglucoselevels,yeastcellsareslowgrowingandshow signi?cantmetabolicchanges[3]. Moreover,thekeyforinterpretingtheeffectofthecyt1 deletiononCRistoexaminetheeffectofthedeletiononlife spanatagivenreducedglucoseconcentration(compared withtheusual2%)andcomparingthiswiththedegreeoflife extensioninthewild