Calorie restriction extends longevity and delays ageing in model organisms and mammals, opposing the onset and progression of an array of age-related diseases. These beneficial effects also extend to the maintenance of brain cognitive functions at later age and to the prevention, at least in rodents, of brain senescence and associated neurodegenerative disorders. In recent years, the molecular mechanisms underlying brain response to calorie restriction have begun to be elucidated, revealing the unanticipated role of a number of key nutrient sensors and nutrient-triggered signaling cascades in the translation of metabolic cues into cellular and molecular events that ultimately lead to increased cell resistance to stress, enhanced synaptic plasticity, and improved cognitive performance. Of note, the brain's role in CR also includes the activation of nutrient-sensitive hypothalamic circuitries and the implementation of neuroendocrine responses that impact the entire organism. The present review addresses emerging molecular themes in brain response to dietary restriction, and the implications of this knowledge for the understanding and the prevention of brain disorders associated with ageing and metabolic disease. © 2012 Springer Basel.
Original languageEnglish
Pages (from-to)3157-3170
Number of pages14
JournalCellular and Molecular Life Sciences
Publication statusPublished - 2013


  • Aging
  • Animals
  • Brain
  • Brain ageing
  • CREB
  • Caloric Restriction
  • Calorie restriction
  • Cell Biology
  • Cellular and Molecular Neuroscience
  • Humans
  • Longevity
  • Molecular Biology
  • Molecular Medicine
  • Neurodegenerative disease
  • Nutrient sensing
  • Pharmacology
  • Stem cell


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