Intervention
MOTS-c
Last updated 2026-07-02· Last reviewed 2026-07-02· 1 min read
Reviewed by the Ultimate Longevity Bible editorial team. Educational reference — not medical advice. See disclaimer.
What it is
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is translated from a small ORF within the mitochondrial genome. It exits the mitochondrion, enters the nucleus, and modulates AMPK and metabolic gene expression.
Evidence
- Preclinical: mouse studies show improved insulin sensitivity, reduced high-fat-diet-induced obesity, enhanced exercise capacity, and skeletal muscle metabolic reprogramming.
- Human observational: lower serum MOTS-c in older adults, T2D, and metabolic-syndrome patients.
- Human interventional: very early — small pilot studies in metabolic disease.
Longevity relevance
Attractive because MOTS-c represents inter-organelle mitochondrial-to-nuclear communication that appears to weaken with age. Human hard-endpoint data is not yet available; the peptide is not in routine clinical use.