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The ligands of the manganese ions are 3 histidine side-chains, an aspartate side-chain and a water molecule or hydroxy ligand, depending on the Mn oxidation state (respectively II and III)

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In recent years, the scientific community has focused on two key endogenous molecules NAD (Nicotinamide Adenine Dinucleotide) and reduced glutathione (GSH) whose progressive depletion with age is now correlated with the main signs of cutaneous and systemic ageing. NAD: the anti-ageing metabolic powerhouse NAD is an essential coenzyme involved in hundreds of redox reactions and a fundamental substrate for sirtuins and PARPs, pro-longevity enzymes that regulate DNA repair and mitochondrial function

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Further supporting melatonins potential impact on brain insulin, a rat study demonstrated that melatonin, upon binding to its membrane-bound receptors, can initiate intracellular pathways in the brain typically activated by insulin binding to the insulin receptor (e.g., AKT serine phosphorylation) [137]

Blood 90:172b, 1997