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 language | English (US) |
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Pages (from-to) | 534-548.e5 |
Journal | Cell metabolism |
Volume | 31 |
Issue number | 3 |
DOIs | |
State | Published - Mar 3 2020 |
Keywords
- YB-1
- aging
- htNSC
- hypothalamus
- neural stem cells
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology