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

Cell Rep. 2016 Jan 26;14(3):422-428. doi: 10.1016/j.celrep.2015.12.042. Epub 2016 Jan 7.

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.

Keywords: HSP70; aldosterone; autophagy; calorie restriction; cortisol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Beclin-1
  • Body Mass Index
  • Caloric Restriction*
  • Cluster Analysis
  • Exercise
  • Female
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / genetics
  • 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

Substances

  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • Transcription Factors
  • light chain 3, human
  • Hydrocortisone
  • molecular chaperone GRP78