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Ketosis & Metabolism

Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor

By Tadahiro Shimazu, Matthew D. Hirschey, Dr. John Newman, MD, PhD et al

Histones are a broad class of proteins that regulate gene expression, in particular by affecting pathways involved in oxidative stress. Histone acetylation increases in animal tissues in response to fasting and calorie restriction, an effect that may be mediated through the inhibition of HDACs, specifically class III HDACs, also known as sirtuins. Calorie restriction and fasting increase levels of the ketone body Beta-Hydroxybutyrate (β-HB) in tissues, and administration of β-HB alone similarly increases histone acetylation in mice tissue and human kidney cells by inhibit class I, II, and III HDACs. Inhibition of HDACs by β-HB increased the expression of the genes Foxo3a and Mt2 and the antioxidant genes MnSOD and catalase, all of which are responsible for oxidative stress resistance. Given that oxidative stress underlies many age-associated pathologies, provision of β-HB in humans using exogenous ketones esters has therapeutic potential to address aging and metabolic conditions associated with elevated levels of oxidative stress.

View the full peer-reviewed scientific paper at National Institutes of Health.

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