title: Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.
abstract: Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.
authors.affiliation: Department of Biological, Geological, and Environmental Sciences, and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, Ohio, USA.
authors.forename: Sonal A
authors.initials: SA
authors.lastname: Patel
authors.affiliation: Department of Biological, Geological, and Environmental Sciences, and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, Ohio, USA.
authors.forename: Amol
authors.initials: A
authors.lastname: Chaudhari
authors.affiliation: Department of Biological, Geological, and Environmental Sciences, and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, Ohio, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Biological, Geological, and Environmental Sciences, and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, Ohio, USA.
authors.forename: Nikkhil
authors.initials: N
authors.lastname: Velingkaar
authors.affiliation: Department of Biological, Geological, and Environmental Sciences, and Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, Ohio, USA r.kondratov@csuohio.edu.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Kondratov
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D031204:Caloric Restriction / Q000379:methods*; D057906:Circadian Clocks / Q000502:physiology*; D005260:Female; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008017:Life Expectancy; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D001786:Blood Glucose; D007328:Insulin; D007334:Insulin-Like Growth Factor I
keywords: aging; food anticipation; gene expression; glucose; insulin; transcription