Game over for non-selective sirtuin agonists

Various sirtuins decrease activity of the pyruvate dehydrogenase complex. Sirtuins can act as lipomidases. Sirtuins as lipomidases remove remove lipoyl modifications from the pyruvate dehydrogenase complex and the 2-oxoglutarate complex inhibiting the pyruvate dehydrogenase complex and the 2-oxoglutarate complex. Sirtuin 4 is a lipomidase.  Sirtuin 2 is a lipomidase. Sirtuins are lipomidases in bacteria. Sirtuin 5 decreases activity of the pyruvate dehydrogenase complex.  The pyruvate dehydrogenase complex E2 subunit and the 2-oxoglutarate complex E2 subunit have as cofactors coenzyme A and lipoic acid. The E2 units are already weak links due to an inability to synthesize coenzyme A. To further weaken the weak links by increasing activity of lipomidases is not a way to treat diseases of aging.

Sirtuins are NAD+ dependent enzymes. Niacin and niacin derivatives would be non-selective agonists of sirtuins. Supplementation with niacin and niacin derivatives is a total disaster on a lot grounds.

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