Energy intake and exercise as determinants of brain health and vulnerability to injury and disease

Cell Metab. 2012 Dec 5;16(6):706-22. doi: 10.1016/j.cmet.2012.08.012. Epub 2012 Nov 15.


Evolution favored individuals with superior cognitive and physical abilities under conditions of limited food sources, and brain function can therefore be optimized by intermittent dietary energy restriction (ER) and exercise. Such energetic challenges engage adaptive cellular stress-response signaling pathways in neurons involving neurotrophic factors, protein chaperones, DNA-repair proteins, autophagy, and mitochondrial biogenesis. By suppressing adaptive cellular stress responses, overeating and a sedentary lifestyle may increase the risk of Alzheimer's and Parkinson's diseases, stroke, and depression. Intense concerted efforts of governments, families, schools, and physicians will be required to successfully implement brain-healthy lifestyles that incorporate ER and exercise.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Brain / metabolism*
  • Caloric Restriction
  • Energy Intake*
  • Exercise*
  • Humans
  • Neurodegenerative Diseases / diet therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurons / metabolism