When neurogenesis encounters aging and disease

Trends Neurosci. 2010 Dec;33(12):569-79. doi: 10.1016/j.tins.2010.09.003. Epub 2010 Oct 18.


In this review, we consider the evidence that a reduction in neurogenesis underlies aging-related cognitive deficits and impairments in disorders such as Alzheimer's disease (AD). The molecular and cellular alterations associated with impaired neurogenesis in the aging brain are discussed. Dysfunction of presenilin-1, misprocessing of amyloid precursor protein and toxic effects of hyperphosphorylated tau and β-amyloid probably contribute to impaired neurogenesis in AD. Because factors such as exercise, environmental enrichment and dietary energy restriction enhance neurogenesis, and protect against age-related cognitive decline and AD, knowledge of the underlying neurogenic signaling pathways could lead to novel therapeutic strategies for preserving brain function. In addition, manipulation of endogenous neural stem cells and stem cell transplantation, as stand-alone or adjunct treatments, seems promising.

Publication types

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

MeSH terms

  • Aging / physiology*
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / physiopathology
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / anatomy & histology
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology*
  • Cognition Disorders* / pathology
  • Cognition Disorders* / physiopathology
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Learning / physiology
  • Memory / physiology
  • Neurogenesis / physiology*
  • Presenilin-1 / metabolism


  • Amyloid beta-Protein Precursor
  • Presenilin-1