Impact of age and caloric restriction on neurogenesis in the dentate gyrus of C57BL/6 mice

Neurobiol Aging. 2004 Mar;25(3):333-40. doi: 10.1016/S0197-4580(03)00083-6.


Age-related changes in neurogenesis and its modulation by caloric restriction (CR) were studied in C57BL/6 mice. To this end, bromodeoxyuridine (BrdU) labeling was used to assess neuronal and glial precursor proliferation and survival in the granular cell layer (GCL) and the hilus of the dentate gyrus of 2-, 12-, 18-, and 24-month-old mice. For both regions, we found an age-dependent decrease in proliferation but not in survival of newborn cells. Interestingly, the reduction in proliferation occurred between 2 and 18 months of age with no additional decline between 18- and 24-month-old mice. Phenotyping of the newborn cells revealed a decrease in the neuron fraction in the GCL between 2 and 12 months of age but not thereafter. The majority of BrdU cells in the hilus colocalized with astrocytic but none with neuronal markers. CR from 3 to 11 months of age had no effect on neurogenesis in the GCL, but had a survival-promoting effect on newly generated glial cells in the hilus of the dentate gyrus. In conclusion, C57BL/6 mice reveal a substantial reduction in neurogenesis in the dentate gyrus until late adulthood with no further decline with aging. Long-term CR does not counteract this age-related decline in neurogenesis but promotes survival of hilar glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / physiology
  • Biomarkers
  • Bromodeoxyuridine
  • Caloric Restriction*
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cell Survival / physiology
  • Dentate Gyrus / cytology
  • Dentate Gyrus / growth & development*
  • Dentate Gyrus / physiology
  • Down-Regulation / physiology
  • Food Deprivation / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism


  • Biomarkers
  • Nerve Tissue Proteins
  • Bromodeoxyuridine