MOTS-c: The Mitochondrial Peptide That Rewrites Exercise Response

Here's what you need to know

Your mitochondria don’t just make ATP. In 2015, researchers discovered that mitochondria encode peptides that function as signaling molecules. One of them, MOTS-c (Mitochondrial open reading frame of the 12S ribosomal RNA type-c), does something extraordinary: it mimics the metabolic effects of exercise at the cellular level.

When you exercise, MOTS-c levels spike in your blood and muscle tissue. The peptide activates AMPK (the master metabolic switch that controls how your cells burn fuel), enhances glucose uptake without insulin, improves insulin sensitivity, and triggers the genes that build new mitochondria.

Here’s what matters for longevity: MOTS-c levels decline as you age. Lower MOTS-c correlates with worse metabolic health (higher BMI, waist circumference, fasting insulin, insulin resistance, and HbA1c). The signal your mitochondria send to regulate metabolism weakens over time.

Good news about MOTS-c: you can inject it.

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