Journal
CELL METABOLISM
Volume 31, Issue 3, Pages 534-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2020.01.002
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Funding
- National Natural Science Foundation of China [81930022, 91749105, 81520108008, 81700785, 81801393, 81873643]
- Natural Science Foundation of Hunan Province of China [S2019JJQNJJ0681]
- innovation-driven project of Central South University [20180033040008]
- Science and Technology Development Plan of Hunan Province in 2017 [2017RS3014]
- Talent Plan of Xiangya Hospital at Central South University [52, 35]
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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 p16(INK4A). 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.
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