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MOTS-C triggers the metabolic stress signal (AMPK), but AMPK activation alone doesn't guarantee increased mitochondrial output SLUPP-332 drives the transcriptional machinery for new mitochondria, but needs the upstream signal to be active 5-Amino-1MQ ensures the NAD+ substrate is available so the newly biogenerated mitochondria can actually function at higher capacity "Targeting three nodes — signal, transcription, and substrate — simultaneously is more likely to produce durable metabolic change than targeting one alone." (Conceptual framework based on published pathway biology

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