Mitochondrial-derived peptide

MOTS-c

Animal / limited humanPromising in mice; human benefit unproven

A mitochondria-encoded peptide that activates the cell's energy sensor and acts like an 'exercise mimetic' in mice — human benefit remains unproven.

✦ 2 min read · 2 sources

What it is

MOTS-c is a 16-amino-acid peptide encoded inside the mitochondrial genome (not the nucleus), discovered in 2015 at USC. It helped establish that mitochondria encode signaling molecules, not just energy.

How it works

It influences the folate one-carbon cycle to raise AICAR, which activates AMPK — the enzyme cells use to sense low energy and switch on fat-burning and glucose uptake. Under stress it also moves from mitochondria into the nucleus to help regulate antioxidant stress-response genes (retrograde signaling).

What the evidence shows

Nearly all efficacy data is preclinical. In mice it prevented diet-induced weight gain and insulin resistance and improved running capacity even in old animals. In humans the evidence is associational only — blood levels decline with age and rise with exercise. The most advanced MOTS-c-based drug program (CohBar's CB4211) passed Phase 1 safety but showed no separation from placebo on its primary endpoint, and was discontinued.

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The honest take

Promising in mice; human benefit unproven

Status & safety

Not FDA-approved for any indication, including anti-aging. Investigational/research compound; flagged by anti-doping authorities (WADA/USADA). Human efficacy data is absent.

Summaries of published, third-party research for educational purposes. Not medical advice; not a claim of efficacy or safety for any use.

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