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Severe kidney disease (end-stage renal disease or eGFR below 15 mL/min/1.73m) represents another critical contraindication

Reduced circulating MOTS-c appears in obesity, type 2 diabetes, and aging, suggesting supplementation may restore youthful metabolic signaling capacity

For example, the cerebellum exhibits relatively high glutathione activity, which contributes to its enhanced resistance to oxidative damage

[] Additionally, mutations in processing enzymes like prohormone convertase 1/3 (encoded by PCSK1 gene) impair proteolytic release of POMC-derived -MSH, causing obesity with glucose dysregulation

As in the proton-catalyzed mechanism, RSO then reacts with GSH in the second step