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RESEARCH PRODUCT

Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle

John O. HolloszyEdda CavaEdda CavaDennis T. VillarealDennis T. VillarealBeatrice BertozziDanilo LicastroNicola VeroneseNicola VeroneseGökhan S. HotamisligilWanda RizzaWanda RizzaLing YangFrancesco SpeltaFrancesco SpeltaLuigi FontanaLuigi Fontana

subject

Male0301 basic medicineGenetics and Molecular Biology (all)Time FactorsHydrocortisoneBiochemistryCortisolBody Mass IndexCluster Analysislcsh:QH301-705.5Endoplasmic Reticulum Chaperone BiPAldosteroneHeat-Shock ProteinsHSP70Serum cortisolMiddle Agedmedicine.anatomical_structureBeclin-1Femalemedicine.symptomMicrotubule-Associated Proteinsmedicine.drugAdultmedicine.medical_specialtyCalorie restrictionInflammationBiologyGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesEndurance trainingInternal medicineHeat shock proteinmedicineAutophagyHumansHSP70 Heat-Shock ProteinsRNA MessengerMuscle SkeletalExerciseCalorie restrictionCaloric RestrictionHydrocortisoneHSP70; aldosterone; autophagy; calorie restriction; cortisol; adult; apoptosis regulatory proteins; beclin-1; body mass index; cluster analysis; exercise; female; gene expression regulation; hsp70 heat-shock proteins; heat-shock proteins; humans; hydrocortisone; male; membrane proteins; microtubule-associated proteins; middle aged; muscle skeletal; RNA messenger; time factors; transcription factors; caloric restrictionCalorie restriction (CR)AutophagyMembrane ProteinsSkeletal muscleHsp70030104 developmental biologyEndocrinologylcsh:Biology (General)Gene Expression RegulationAldosterone; Autophagy; Calorie restriction; Cortisol; HSP70; Biochemistry Genetics and Molecular Biology (all)Apoptosis Regulatory ProteinsTranscription Factors

description

Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles. © 2016 The Authors.

10.1016/j.celrep.2015.12.042http://hdl.handle.net/11379/478562