Reducing Hypothalamic Stem Cell Senescence Protects against Aging-Associated Physiological Decline

Yu Zhong Xiao, Mi Yang, Ye Xiao, Qi Guo, Yan Huang, Chang Jun Li, Dongsheng Cai, Xiang Hang Luo

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Age-dependent loss of hypothalamic neural stem cells (htNSCs) is important for the pathological consequences of aging; however, it is unclear what drives the senescence of htNSCs. Here, we report that a long non-coding RNA, Hnscr, is abundantly expressed in the htNSCs of young mice but decreases markedly in middle-aged mice. We show that depletion of Hnscr is sufficient to drive the senescence of htNSCs and aging-like phenotypes in mice. Mechanistically, Hnscr binds to Y-box protein 1 (YB-1) to prevent its degradation and thus the attenuation of transcription of the senescence marker gene p16INK4A. Through molecular docking, we discovered that a naturally occurring small compound, theaflavin 3-gallate, can mimic the activity of Hnscr. Treatment of middle-aged mice with theaflavin 3-gallate reduced the senescence of htNSCs while improving aging-associated pathology. These results point to a mediator of the aging process and one that can be pharmacologically targeted to improve aging-related outcomes.

Original languageEnglish (US)
Pages (from-to)534-548.e5
JournalCell metabolism
Volume31
Issue number3
DOIs
StatePublished - Mar 3 2020

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Keywords

  • YB-1
  • aging
  • htNSC
  • hypothalamus
  • neural stem cells

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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