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

• Published in: Cell reports (Cambridge) Vol. 14; no. 3; pp. 422 - 428
• Main Authors: Yang, Ling, Licastro, Danilo, Cava, Edda, Veronese, Nicola, Spelta, Francesco, Rizza, Wanda, Bertozzi, Beatrice, Villareal, Dennis T., Hotamisligil, Gökhan S., Holloszy, John O., Fontana, Luigi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.01.2016; Elsevier
• Subjects: Adult; aldosterone; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; autophagy; Beclin-1; Body Mass Index; Caloric Restriction; calorie restriction; Cluster Analysis; cortisol; Exercise; Female; Gene Expression Regulation; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; HSP70; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Humans; Hydrocortisone - blood; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Middle Aged; Muscle, Skeletal - metabolism; RNA, Messenger - metabolism; Time Factors; Transcription Factors - genetics; Transcription Factors - metabolism; cortisol; calorie restriction; HSP70; autophagy; aldosterone
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.12.042

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. [Display omitted] •Calorie restriction increases health-span and lifespan in model organisms•Little is known about the metabolic and molecular effects of CR in humans•CR inhibits inflammation in part by increasing serum cortisol concentration•CR elevates expression of genes and proteins that enhance protein quality control Yang et al. show that calorie restriction without malnutrition in humans inhibits inflammation, at least in part by elevating serum cortisol concentration, and increases chaperone and autophagy genes and proteins involved in protein quality control and organelle homeostasis in the removal of dysfunctional proteins and organelles from cell.