MOTS-c vs SHLP-6
MOTS-c has observational human work and a registered native intervention without cited outcomes; SHLP-6 has cell, fish and limited human observation evidence without an administered-human result.
Last updated: September 28, 2026
Dossier labels summarize each dossier's research scope. They do not establish comparative treatment benefit or safety. Read the comparison below in that context.
MOTS-c
Dossier overview
SHLP-6
Dossier overview
Distinct preclinical questions
MOTS-c is encoded in mitochondrial 12S rRNA and has metabolic model findings. SHLP-6 is a small humanin-like peptide from the 16S region. Its sequence and formulation require care: a 2023 genetics analysis predicted a canonical human 20-residue sequence, while older page metadata called it 22 residues. MOTS-c discovery, PMID 25738459 · SHLP-6 genetics, PMID 37675281
| Evidence question | MOTS-c | SHLP-6 |
|---|---|---|
| Human observations | Endogenous exercise, diabetes and sleep-apnea measurements | Exercise-associated circulating levels and placental transcripts |
| Direct intervention | Mouse/cell research; native Phase 2 registration without outcome | Cell and zebrafish experiments, preliminary mouse abstract; no cited human administration |
| Therapeutic-claim grade | Low | Very low |
MOTS-c mouse experiments have tested glucose-related and age-related physical measures. A 2026 C26 mouse/cell cachexia paper found partial skeletal-muscle preservation with preventive exposure but no preservation of total body or fat mass. Human observations of endogenous MOTS-c, including a 2026 study with no arterio-venous exercise difference, are not administered-peptide effects. PMID 33473109 · PMID 41520850 · PMID 42266945
The original SHLP-6 paper reported DNA-fragmentation apoptosis in cultured NIT-1 and 22Rv1 cells; it did not show selective cancer-cell or senescent-cell removal. A later study found FPR1/FPR2 signaling in engineered cells, without showing that this drives the apoptosis result. Zebrafish oxidative-stress experiments test still different endpoints. PMID 27070352 · PMID 39294930 · PMID 40292418 · PMID 40915070
One human exercise study measured endogenous SHLP-6 in ten men; a placental study measured SHLP-6 mRNA, not administered peptide or SHLP-6 protein in that cohort. PMID 32271093 · PMID 42453115
NCT07505745 registers native MOTS-c Phase 2 intervention without a cited outcome; NCT03998514 studied the distinct CB4211 analog. Neither establishes a SHLP-6 combination or human safety. FDA compounding safety review
This page is an evidence summary, not a therapeutic recommendation.
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Disclaimer: This comparison is for educational purposes only and does not constitute medical advice. Individual responses to medications vary. Always consult a qualified healthcare provider before making treatment decisions.