Can deleterious epigenetic changes be reversed by supplemental alpha ketoglutarate?


TET enzymes are 2-oxoglutarate dependent.enzymes that are instrumental in DNA demethylation. JmjC domain-containing proteins, which are 2-oxoglutarate dependent.enzymes, demethylate histones.

Research indicates that 2-oxoglutarate by affecting TET and Jmjc domain-containing proteins can have epigenetic effects reversing epigenetic changes arising from dysregulation of the tricarboxylic acid (TCA) cycle. The TCA cycle synthesizes 2-oxoglutarate.

I have been stressing in this blog that with a dysregulation of iron-sulfur cluster formation there is a dysregulation of aconitase which is an iron-sulfur protein early in the TCA cycle With aconitase dysregulated the TCA cycle is dysregulated. Another enzyme in the TCA cycle, succinate dehydrogenase, also has iron-sulfur clusters.

Could deleterious epigenetic changes in humans, due to dysregulation of the TCA cycle, be reversed by supplemental alpha-ketoglutarate? That has not yet been established.

2-oxoglutarate-dependent dioxygenases are involved in aging, 2-oxoglutarate could be a longevity supplement. A rule of thumb in regards to longevity supplements is never take a longevity supplement for longevity that does not have immediate positive benefits as absent immediate positive benefits knowing whether one is going in the correct direction is unknowable . If 2-oxoglutarate proves to be useful in the treatment of various neurological illnesses but also increases longevity so much the better.

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