Educational reference, not medical advice. This page summarizes information from published research and regulatory filings for educational purposes. It is not a recommendation to use any compound and should not replace guidance from a licensed healthcare provider. Most peptides discussed here are not approved for the uses described.
What it is
Humanin is a 24-amino-acid peptide encoded within the mitochondrial 16S ribosomal RNA gene — a "small open reading frame" peptide that established the concept of mitochondrial-derived peptides as functional signaling molecules. The peptide is produced both inside cells and secreted into circulation, where it is detectable in human plasma at picomolar to nanomolar concentrations.
It is the founding member of a family that now includes the MOTS-c peptide (encoded in the 12S rRNA) and the SHLP peptides. The recognition that the mitochondrial genome encodes secreted signaling peptides — not just respiratory chain components — was a substantive shift in mitochondrial biology in the 2000s and 2010s.
History
Humanin was first reported in 2001 by Yuichi Hashimoto and colleagues in the Nishimoto lab at Keio University, in a paper published in Proceedings of the National Academy of Sciences. The discovery came from a functional screen of cDNAs that could rescue neuronal cell lines from beta-amyloid-induced death. The active sequence mapped back to the mitochondrial 16S rRNA region.
Pinchas Cohen's group at the University of Southern California took the lead on subsequent characterization through the 2000s and 2010s, expanding the biology to metabolism, cardioprotection, and stress resistance. Cohen's group also identified MOTS-c and the SHLP family from the same mitochondrial small-ORF concept.
Humanin levels in human plasma decline with age, and circulating concentrations correlate with health metrics in several observational cohorts. Despite a substantial body of preclinical biology, humanin has not advanced to a registered drug development program.
Regulatory status
Humanin is not approved by any regulator. ClinicalTrials.gov does not list registered trials of exogenous humanin or any approved analog as a therapeutic. The peptide is not on the FDA 503A compounding list, and compounding pharmacies in the United States cannot legally prepare it for patients. Sold through research peptide channels with not-for-human-use labeling.
A stabilized analog, S14G-humanin (with a single amino acid substitution that increases potency roughly 1000-fold in some in vitro assays), has been studied preclinically and is sometimes sold separately.
How researchers describe its action
Published mechanism work describes humanin acting through at least two receptor systems: a heterotrimeric receptor complex involving CNTFR, WSX-1, and gp130 (the same family as the IL-6 receptor), and direct interaction with intracellular Bcl-2-family proteins to inhibit apoptosis. Downstream effects in cell and animal models include suppression of neuronal apoptosis, improved insulin sensitivity, attenuated atherosclerosis progression, and cardioprotection in ischemia-reperfusion injury.
These are consistent findings across multiple labs in multiple model systems. None have been confirmed in human clinical trials.
Half-life and dosing intervals
Native humanin has a very short plasma half-life — under 30 minutes in published rodent pharmacokinetic studies. Synthetic analogs with sequence modifications (most notably S14G-humanin) have somewhat longer half-lives but remain short compared with albumin-bound peptides like the GLP-1 agonists.
There is no established human dose. In rodent neuroprotection studies, intracerebroventricular doses in the nanogram range and intraperitoneal doses in the milligram-per-kilogram range have both been reported, with substantial variation between studies. The doses described in observational human use online — typically 2 to 10 mg per day subcutaneously — are extrapolations without controlled human pharmacokinetic support.
Reconstitution example
Humanin is supplied lyophilized in small vials, typically 5 mg or 10 mg. A 5 mg vial reconstituted with 2 mL of bacteriostatic water yields 2.5 mg/mL. On a 1 mL U-100 insulin syringe, 20 units (0.2 mL) delivers 500 mcg, and 40 units (0.4 mL) delivers 1 mg. Vial's calculator handles the conversion when vial mass and water volume are entered.
What to know
- Preclinical only. All published efficacy evidence is in cultured cells, rodents, or as circulating biomarker associations in human cohorts. No interventional human trial of exogenous humanin has been published.
- Endogenous biology is well established. Humanin is a real, secreted mitochondrial peptide whose plasma levels decline with age. The question is whether exogenous administration meaningfully restores its activity in tissue, and at what dose.
- Two molecules in circulation. Native humanin (24 aa) and S14G-humanin (a high-potency analog) are sometimes sold under the same name. They are not interchangeable.
- Storage. Lyophilized: refrigerate, protect from light. Reconstituted: refrigerate and use within 2 to 4 weeks per typical short-peptide stability data.
- Safety profile is incomplete. No long-term human safety trial exists. User reports describe injection-site irritation as the most common observation; rare or delayed effects are uncharacterized.
Sources
- 1.Hashimoto Y et al. (2001). A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proceedings of the National Academy of Sciences.
- 2.Yen K et al. (2013). The emerging role of the mitochondrial-derived peptide humanin in stress resistance. Journal of Molecular Endocrinology.
- 3.Hazafa A et al. (2021). Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases. Life Sciences.
- 4.Rochette L et al. (2020). Mitochondrial-derived peptides: New markers for cardiometabolic dysfunction. Archives of Cardiovascular Diseases.