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Cell Metab. 2020 Mar 3;31(3):534-548.e5. doi: 10.1016/j.cmet.2020.01.002. Epub 2020 Jan 30.

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

Author information

1
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
2
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan 410008, China.
3
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: dongsheng.cai@einstein.yu.edu.
4
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China. Electronic address: xianghangluo@sina.com.

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.

KEYWORDS:

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

PMID:
32004475
DOI:
10.1016/j.cmet.2020.01.002

Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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