Humanin

Category: Peptides · Last updated 2026-05-20

Humanin is a 24-amino-acid peptide encoded by a short open reading frame within the mitochondrial 16S rRNA region. It was identified in 2001 by Hashimoto et al. in a screen for proteins that protect against amyloid-β (Aβ)-induced neuronal cell death. It is the founding member of the mitochondrial-derived peptide family alongside MOTS-c and SHLP1-6.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / Humanin](https://peppudex.com/peptides/humanin).

Overview

Humanin is encoded within the mitochondrial DNA at a short open reading frame embedded in the 16S rRNA gene. Despite being mitochondrially encoded, the peptide is secreted and acts as a cell-signaling molecule on multiple cell types. Plasma humanin levels decline with age in human cohort studies, and elevated plasma humanin is associated with longevity in centenarian and offspring-of-centenarian cohorts.

Multiple variants and analogs have been studied. The S14G-Humanin (HNG) analog substitutes glycine for serine at position 14 and shows 1000-fold higher potency in neuroprotection assays than wild-type humanin. The colivelin analog fuses humanin with ADNF-C and is studied for ALS and neurodegeneration models.

Mechanism

Multiple receptor and intracellular target families:

Apoptosis inhibition. Humanin binds and inhibits the pro-apoptotic BH3-only proteins Bax, Bid, and tBid, preventing mitochondrial outer-membrane permeabilization and downstream cytochrome-c release.
Cell-surface receptor signaling. Humanin engages a heterotrimeric receptor complex of CNTFR / WSX-1 / gp130 and activates downstream STAT3 + ERK pathways.
IGFBP-3 interaction. Humanin binds insulin-like growth factor binding protein 3, modulating IGF-1 bioavailability and insulin sensitivity.
Mitochondrial protection. Direct effects on mitochondrial respiratory chain function and ROS production in stressed cells.

See: Mitochondrial-derived_peptides, MOTS-c.

Evidence

Key publications:

Hashimoto Y, Niikura T, Tajima H, et al. "A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ." Proc Natl Acad Sci USA. 2001;98(11):6336-41. [PMID 11371646](https://pubmed.ncbi.nlm.nih.gov/11371646/). (Discovery paper.)
Muzumdar RH, Huffman DM, Atzmon G, et al. "Humanin: a novel central regulator of peripheral insulin action." PLoS One. 2009;4(7):e6334. [PMID 19623253](https://pubmed.ncbi.nlm.nih.gov/19623253/).
Yen K, Mehta HH, Kim SJ, et al. "The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan." Aging (Albany NY). 2020;12(12):11185-11199. [PMID 32584785](https://pubmed.ncbi.nlm.nih.gov/32584785/).

Pharmacokinetics

Native humanin has a short plasma half-life (minutes) consistent with rapid proteolytic clearance. Engineered analogs (S14G-HN, colivelin) extend stability for research dosing. Most published animal studies use intraperitoneal or intracerebroventricular delivery to bypass blood-brain barrier transport limits.

Dosing literature

Animal research typically uses 1 to 10 mg/kg intraperitoneal in rodent models. This wiki does not recommend any human dose. Humanin is not FDA-approved for any indication and is supplied as a research-grade chemical reference compound for in-vitro use only.

Storage

Lyophilized: 2 to 8 °C, stable 12+ months protected from light. Reconstituted: 2 to 8 °C, use within 14 days. See Reconstitution.

Regulatory status

United States. Not FDA-approved. Investigational / research-only.
WADA. Not currently on the WADA Prohibited List as of the 2026 publication.

Side effects (from animal studies)

No major adverse-event signals have been reported in published rodent studies at standard research doses. Human safety data are limited. As a pleiotropic signaling peptide, theoretical concerns exist around tumor-suppressor cross-talk in malignancy contexts.

References

Hashimoto Y, et al. PNAS 2001. [PMID 11371646](https://pubmed.ncbi.nlm.nih.gov/11371646/)
Muzumdar RH, et al. PLoS One 2009. [PMID 19623253](https://pubmed.ncbi.nlm.nih.gov/19623253/)
Yen K, et al. Aging 2020. [PMID 32584785](https://pubmed.ncbi.nlm.nih.gov/32584785/)

Research framing only. Peppu Wiki documents the published research literature surrounding peptide compounds. Articles describe in-vitro and animal-model evidence, regulatory status, and community-reported protocols. Nothing on this site is medical advice, a recommendation for human use, or a substitute for consultation with a qualified clinician. All compounds discussed are research-use only. Citations should be verified at the source before relying on any quantitative claim.

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