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Pharmacological inhibition of cyclophilin D is only effective before this threshold is crossed, defining a narrow therapeutic window ( Together, these observations establish that perioperative mitochondrial dysfunction arises from the integrated action of ROS, RNS, Ca 2+ overload, and mPTP dynamicsnot ROS alone

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Agerelated declines of 13 % per year in GH, melatonin, and cortisol further underscore the need for targeted interventions