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A 16-amino-acid mitochondrial messenger that mimics exercise at the cellular level — activating AMPK, reprogramming metabolism, and writing survival instructions directly into the nucleus. The science is striking. The stability problem is brutal.
MOTS-c is a mitochondrial-derived peptide (mitokine) that acts as an exercise mimetic through the Folate-AICAR-AMPK axis. It translocates to the nucleus under metabolic stress, enhances glucose uptake via GLUT4, promotes white-to-brown fat conversion, and reprograms immune cells toward anti-inflammatory phenotypes. A natural longevity variant (K14Q) exists in East Asian populations. Clinical translation is hampered by extreme instability (85–90% activity loss in 2–3 hours at room temperature) and a circulating half-life of only 1–2 hours.