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Biomolecule β-Hydroxybutyrate – key to vascular youth?

One of the hallmarks of old age is vascular aging. Researchers found that a biomolecule, β-Hydroxybutyrate (BHB), can serve as a key to turning the time around. Apparently, BHB has anti-aging effects on the vascular system.

 

 

 

β-Hydroxybutyrate – a biomolecule

 

Beta-hydroxybutyrate biomolecule
Molecular structure of the biomolecule, β-Hydroxybutyrate

 

β-Hydroxybutyrate is a biomolecule with a chemical formula, C4H803. Many regard it as a ketone; however, under a strict definition, it would not technically fit as a ketone. That is because its carbonyl carbon binds to only one instead of two other carbon atoms. Nonetheless, BHB appears to be physiologically related to other ketone bodies (such as acetate and acetoacetate) based on the metabolic aspect. For instance, the tissue level of BHB rises during calorie restrictions, fasting, prolonged intense workout, and when following a ketogenic diet.1 Accordingly, BHB level occurs the highest among the three circulating ketones in the body.

 

 

 

β-Hydroxybutyrate – biological sources

The body naturally produces BHB through the process of ketogenesis. Low-carb diet and fasting lead to the rise of BHB level. Firstly, the body breaks down fatty acids to produce acetyl CoA. This precursor goes through a series of reactions leading to acetoacetate synthesis. In turn, the acetoacetate circulates via the bloodstream, and subsequently reaches the liver. The BHB-dehydrogenase enzyme in the liver reduces the acetoacetate to BHB. 1

 

Another biochemical pathway that leads to the synthesis of this biomolecule uses butyrate. The body metabolizes butyrate and produce D-β-hydroxybutyrate through the aid of the enzyme, hydroxybutyrate-dimer hydrolase.

 

 

 

β-Hydroxybutyrate –  biological action

In humans, D-β-hydroxybutyric acid is one of the major endogenous agonist of hydroxycarboxylic acid receptor 2 (HCA2), a receptor protein encoded by the HCAR2 gene. It binds to and activates HCA2. Upon activation, HCA2 can inhibit the breakdown of fats and mediates niacin-induced flushing. Moreover, it induces the dilation of blood vessels.

 

Based on recent research, BHB might serve as a biomolecule that could help turn time around for the vascular system. Old age faces an increased risk to cancer and cardiovascular diseases since the vasculature ages as well. Dr. Ming-Hui Zou, director at Georgia State University, explains. “When people become older, the vessels that supply different organs are the most sensitive and more subject to aging damage….”2

 

 

β-Hydroxybutyrate –  vascular study

biomolecule for vascular youth
The biomolecule, β-Hydroxybutyrate, apparently has anti-aging effects, particularly keeping the vascular system young

 

Zou et al. 2, 3 conducted a study on vascular aging, exploring the link between calorie restrictions and delayed vascular aging. Accordingly, calorie restrictions averted vascular aging.

 

They found that BHB, the biomolecule naturally produced from the liver, has anti-aging effects, particularly on endothelial cells. The endothelial cells line the interior surface of the vascular system. Based on the results, BHB promoted mitosis of endothelial cells, thus, pre-empting vascular aging.3 Furthermore, they saw that BHB binds to a certain protein, which stimulates a series of reactions that consequently rejuvenate, thus, keep the blood vessels young.2

 

 

 

BHB could eventually become a biomolecular tool that promotes mitosis of endothelial cells. In being able to do so, it could help prevent endothelial cell senescence. Hence, this potential rejuvenating effect on the vascular system may soon become valuable not just in keeping the blood vessels young but also in preventing cardiovascular diseases related to old age.

 

 

— written by Maria Victoria Gonzaga

 

 

 

References:
1 Martins, N. (2018 Sept. 26). Beta-hydroxybutyrate or BHB –All You Need to Know. Retrieved from https://hvmn.com/blog/exogenous-ketones/beta-hydroxybutyrate-or-bhb-all-you-need-to-know
2 Georgia State University. (2018 Sept. 10). Researchers Identify Molecule With Anti-Aging Effects On Vascular System. Retrieved from https://www.technologynetworks.com/neuroscience/news/fasting-molecule-delays-vascular-aging-309380
3 Han, Y. M., Bedarida, T., Ding, Y., Somba, B. K., Lu, Q., Wang, Q., Song, P., & Zou, M.H. (2018). β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4. Molecular Cell, 71(6):1064-1078.e5. https://doi.org/10.1016/j.molcel.2018.07.036