The proliferation of amplifying neural progenitor cells is impaired in the aging brain and restored by the mTOR pathway activation

Jennifer Romine, Xiang Gao, Xiao Ming Xu, Kwok Fai So, Jinhui Chen

Research output: Contribution to journalArticle

26 Scopus citations


A decrease in neurogenesis in the aged brain has been correlated with cognitive decline. The molecular signaling that regulates age-related decline in neurogenesis is still not fully understood. We found that different subtypes of neural stem cells (NSCs) in the hippocampus were differentially impaired by aging. The quiescent NSCs decreased slowly, although the active NSCs exhibited a sharp and dramatic decline from the ages of 6-9months and became more quiescent at an early stage during the aging process. The activity of the mammalian target of rapamycin (mTOR) signal pathway is compromised in the NSCs of the aged brain. Activating the mTOR signaling pathway increased NSC proliferation and promoted neurogenesis in aged mice. In contrast, inhibiting the mTOR signaling pathway decreased NSCs proliferation. These results indicate that an age-associated decline in neurogenesis is mainly because of the reduction in proliferation of active NSCs, at least partially because of the compromise in the mTOR signaling activity. Stimulating the mTOR signaling revitalizes the NSCs, restores their proliferation, and enhances neurogenesis in the hippocampus of the aged brain.

Original languageEnglish (US)
Pages (from-to)1716-1726
Number of pages11
JournalNeurobiology of Aging
Issue number4
StatePublished - Apr 1 2015



  • Aging
  • MTOR
  • Neurogenesis
  • Proliferation
  • Stem cell

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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