title: Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle.
abstract: 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.
authors.affiliation: Department of Genetics and Complex Diseases and Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: CBM Scrl-Genomics, Area Science Park, Basovizza, 34149 Trieste, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Licastro
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Experimental Medicine, University of Rome "La Sapienza," 00161 Rome, Italy.
authors.forename: Edda
authors.initials: E
authors.lastname: Cava
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Geriatrics, Department of Medicine, University of Padova, 35128 Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, University of Verona, 37129 Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Spelta
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Food and Human Nutrition Science, University Campus Bio-Medico, 00128 Rome, Italy.
authors.forename: Wanda
authors.initials: W
authors.lastname: Rizza
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bertozzi
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA; Baylor College of Medicine and Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA.
authors.forename: Dennis T
authors.initials: DT
authors.lastname: Villareal
authors.affiliation: Department of Genetics and Complex Diseases and Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Gökhan S
authors.initials: GS
authors.lastname: Hotamisligil
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: John O
authors.initials: JO
authors.lastname: Holloszy
authors.affiliation: Division of Geriatrics and Nutritional Sciences and Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Clinical and Experimental Sciences, Brescia University, 25121 Brescia, Italy; CEINGE Biotecnologie Avanzate, 80122 Napoli, Italy. Electronic address: lfontana@dom.wustl.edu.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fontana
mesh_terms: D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000071186:Beclin-1; D015992:Body Mass Index; D031204:Caloric Restriction; D016000:Cluster Analysis; D000091342:Endoplasmic Reticulum Chaperone BiP; D015444:Exercise; D005260:Female; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D006854:Hydrocortisone
keywords: HSP70; aldosterone; autophagy; calorie restriction; cortisol