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In mouse brain, DR led to a 7-fold increase in GPD2 persulfidation, but no significant increase in GPD1 persulfidation ( H 2 S has been shown to be essential for DR-induced longevity ( 2 S-generating enzyme MPST, resulting in increased mitochondrial ETC function and increased exercise endurance (Sprenger et al., 2025), as the H 2 S generated by the metabolism of endogenous skeletal muscle ergothioneine was shown to increase mitochondrial ETC activity through the transfer of electrons from H 2 S to ubiquinone (Landry et al., 2018)

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54.14mg reported GHK-Cu content Janoshik #168141 Supplemental GHK-Cu 50mg PP2602-012AA endotoxin Janoshik endotoxin report #168137 Janoshik #168137 Supplemental GHK-Cu 50mg PP2602-012AB endotoxin Janoshik endotoxin report #168144 Janoshik #168144 Laboratory Research Use Only

Together, the dual strategy of using litter mate comparisons and C57BL6J back crossed animals increases our confidence that any changes observed are due to differences related to BH 4 deficiency rather than other strain- or litter-related confounders