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

23 Citations (Scopus)

Abstract

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
Pages (from-to)1716-1726
Number of pages11
JournalNeurobiology of Aging
Volume36
Issue number4
DOIs
StatePublished - Apr 1 2015

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Neural Stem Cells
Sirolimus
Stem Cells
Neurogenesis
Brain
Hippocampus
Cell Proliferation
Signal Transduction

Keywords

  • Aging
  • MTOR
  • Neurogenesis
  • Proliferation
  • Stem cell

ASJC Scopus subject areas

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

Cite this

The proliferation of amplifying neural progenitor cells is impaired in the aging brain and restored by the mTOR pathway activation. / Romine, Jennifer; Gao, Xiang; Xu, Xiao-Ming; So, Kwok Fai; Chen, Jinhui.

In: Neurobiology of Aging, Vol. 36, No. 4, 01.04.2015, p. 1716-1726.

Research output: Contribution to journalArticle

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