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(2008) described the discovery and characterization of the tissue-protective EPO receptor (now called the innate repair receptor) and demonstrated that engineered EPO derivatives lacking erythropoietic activity retained cytoprotective signaling, laying the foundation for ARA-290 development [2]

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In parallel, mitochondria influence nuclear epigenetic regulation by generating metabolic intermediates and cofactors, encompassing acetyl-CoA, NAD+, S-adenosylmethionine (SAM), and -ketoglutarate (-KG)which function as substrates for chromatin-modifying enzyme [4]