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  • β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

Molecular cell (2018-09-11)
Young-Min Han, Tatiana Bedarida, Ye Ding, Brian K Somba, Qiulun Lu, Qilong Wang, Ping Song, Ming-Hui Zou
ABSTRACT

β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which significantly inhibits both stress-induced premature senescence and replicative senescence through p53-independent mechanisms. Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a direct binding target of β-HB. β-HB binding to hnRNP A1 markedly enhances hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA, which stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key factor against DNA damage-induced senescence. Finally, fasting and intraperitoneal injection of β-HB upregulate Oct4 and Lamin B1 in both vascular smooth muscle and endothelial cells in mice in vivo. We conclude that β-HB exerts anti-aging effects in vascular cells by upregulating an hnRNP A1-induced Oct4-mediated Lamin B1 pathway.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sucrose, ≥99.5% (GC), BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Sodium butyrate, 98%
Sigma-Aldrich
Ethyl (R)-(−)-3-hydroxybutyrate, 98%
Sigma-Aldrich
(S)-(+)-4-Amino-3-hydroxybutyric acid, 97%