Source Cell Metabolism
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, it’s reported that a long non-coding RNA, Hnscr, is abundantly expressed in the htNSCs of young mice but decreases markedly in middle-aged mice.
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, it’s was 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.