High-fat diet and NAD+ replenishment can rescue Cockayne Syndrome

 

Cockayne syndrome (CS), inherited in an autosomal recessive pattern, is mainly indentified by impaired development of nervous system and premature aging. This condition is caused by the mutation in genes encoding DNA repair protein, CSA or CSB. Scheibye-Knudsen et al. demonstrated high-fat diet, the inhibition of β-hydroxybutyrate (β-OHB), and the elevation of  NAD⁺ levels, may have the effect to rescue premature aging through activating Sirtuin1 (SIRT 1) signaling. The article was published on Cell Metabolism.

 

It is well-established that diet is one of the interventions that can affect neurodegenerative process. On Csb mutated Csb^m/m mice, researchers conducted a experiment including three treatment: high-fat, caloric-restricted, or resveratrol-supplemented diet. They found high-fat diet can normalize the metabolic disorder and some of the neurological dysfunction without adverse effects on Csb^m/m mice. By further investigation, researchers found premature aging in CSB-deficient mice and cells resulted from abnormal activation of poly-ADP-ribose polymerase (PARP), caused a reduction of SIRT1 activity and mitochondrial dysfunction. Also, CSB deficiency led to NAD/NADH equilibrium. Afterwards, researchers noticed that β-OHB, PARP inhibition, or NAD⁺ replenishment can normalized CS-related phenotypes by activating SIRT1. The study reveals two metabolites, β-OHB and NAD⁺, may have effect on CS, and provides a novel therapeutic method for the sever incurable syndrome.

 

Reference:
Cell Metabolism. 2014 Nov 4;20(5):840-855.

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Sirtuin PARP