Humanin

Humanin (HN) is a 21-amino-acid peptide discovered in 2001 through functional screening of cDNA libraries derived from the preserved region of brains of patients with Alzheimer's disease. Unlike classical peptide hormones derived from secretory pathway proteins, Humanin is encoded in a short open reading frame within the 16S ribosomal RNA region of the mitochondrial genome — a landmark finding that established it as the founding member of the mitochondrially derived peptide (MDP) family, a class of small peptides now understood to be encoded by mitochondrial DNA and to act as hormones and cytokines coordinating cellular stress responses.

Humanin's primary studied receptor interactions include three distinct binding partners: gp130 (a cytokine receptor co-subunit shared with IL-6 class cytokines), the heterotrimeric receptor complex formed by CNTF receptor alpha (CNTFRa) with gp130 and LIF receptor beta (LIFRb), and formyl peptide receptor-like 1 (FPRL1). Through gp130 and the CNTFR/gp130/LIFRb complex, Humanin activates the JAK2/STAT3 signaling cascade — the same pathway used by several neuroprotective cytokines — and promotes anti-apoptotic gene expression via transcriptional upregulation of Bcl-2 family members. The FPRL1 interaction mediates some of Humanin's reported anti-inflammatory effects in macrophage and monocyte models. An additional axis involves insulin-like growth factor 1 (IGF-1) binding protein 3 (IGFBP-3), to which Humanin binds and inhibits IGFBP-3-mediated apoptosis, providing a survival signal in contexts of growth factor withdrawal.

Humanin is also studied for its effects on the ApoER2/LRP8 receptor, a member of the low-density lipoprotein receptor family expressed on neurons. Through this receptor, Humanin has been shown to block amyloid-beta toxicity in neuronal cultures by competing with APOE-mediated effects on ApoER2-dependent pathways. This anti-Alzheimer-like mechanism in cell culture was the original discovery context for the peptide and remains a major research application. Peptides.SO tracks 21 Humanin listings from 16 distinct suppliers, all currently in stock, with per-mg pricing from $5.60 to $475.00 and a median of $55.00/mg.

Potential Research Applications: Mitochondrially derived peptide (MDP) biology and mitochondria-to-nucleus retrograde signaling research Neuroprotection against amyloid-beta toxicity and Alzheimer's disease model studies JAK2/STAT3 pathway activation via gp130 and CNTFR/gp130/LIFRb receptor complex signaling FPRL1-mediated anti-inflammatory effects in macrophage and monocyte models IGFBP-3 interaction and apoptosis inhibition in growth-factor-withdrawal models ApoER2/LRP8 receptor signaling and APOE pathway modulation in neuronal cultures Cytoprotection in ischemia-reperfusion and oxidative stress models Metabolic research including glucose metabolism and insulin sensitivity studies in aging models Comparative MDP research alongside MOTS-c and SS-31

Marketplace Snapshot (September 2026, Peptides.SO listings data): Tracked listings: 21 from 16 distinct suppliers (21 in stock, all mg-denominated) Median price per mg: $55.00 (interquartile range $16.00 – $110.00/mg) Lowest verified per-mg price: $5.60/mg Note: Humanin is a lower-volume research peptide relative to BPC-157 or GHRP-family peptides, which contributes to its higher median price per milligram and the smaller number of active suppliers.

Frequently Asked Questions: Q: What is a mitochondrially derived peptide (MDP), and why is Humanin's MDP status significant? A: Mitochondrially derived peptides are small peptides encoded by open reading frames within mitochondrial DNA — a departure from the conventional understanding that mitochondrial genes exclusively encode rRNAs, tRNAs, and the 13 subunits of the oxidative phosphorylation complex. Humanin was the first MDP identified, establishing proof-of-concept that mitochondria contain additional coding capacity beyond the canonical 13 proteins. This implies a signaling layer — MDPs appear to function as cellular stress sensors and communicators, with circulating concentrations changing in response to energy deficit, disease, and aging.

Q: Through what receptors does Humanin exert its neuroprotective effects? A: Humanin has three main receptor routes. The first is the heterotrimeric CNTFR/gp130/LIFRb complex on neurons, which activates JAK2/STAT3 to induce Bcl-2-family anti-apoptotic genes. The second is ApoER2 (also called LRP8), through which Humanin competes with amyloid-beta-associated toxicity. The third is IGFBP-3 binding, which inhibits IGFBP-3-driven apoptosis in growth-factor-deprived cells. Together these pathways give Humanin a multi-pronged cytoprotective profile.

Q: How does Humanin compare with MOTS-c and SS-31 as MDP research subjects? A: All three are mitochondrially derived peptides but differ in mechanism and primary research focus. Humanin is primarily studied for neuroprotection and anti-apoptotic signaling via gp130 and ApoER2. MOTS-c (also encoded in the mitochondrial 12S rRNA gene) is primarily studied for metabolic effects — glucose utilization, AMPK pathway activation, and exercise mimetic effects. SS-31 (Elamipretide) is a synthetic peptide targeting the inner mitochondrial membrane and cardiolipin to protect oxidative phosphorylation capacity. Researchers studying the MDP class often use all three as a comparative panel.

Q: How many suppliers offer Humanin for research purchase? A: Peptides.SO tracks 21 listings from 16 distinct suppliers. It is a lower-volume specialty peptide, so sourcing options are more limited than for BPC-157 or GHRP-family compounds. Pricing is correspondingly higher, with a median of $55/mg.

Q: Is Humanin approved for human use? A: No. Humanin is an unapproved research chemical. All material on this platform is sold strictly for preclinical and in vitro laboratory investigation and is not for human or veterinary consumption.

Related Research on Peptides.SO: peptides.so/learn/humanin-mitochondrial-derived-peptide-cytoprotection-research peptides.so/learn/humanin-vs-mots-c-vs-ss-31-mitochondrial-peptides-compared peptides.so/peptide/mots-c peptides.so/peptide/ss-31 peptides.so/learn/peptide-storage-best-practices peptides.so/tools/calculator

Cited Research: 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 Abeta. Proc Natl Acad Sci U S A. 2001;98(11):6336-6341. PubMed PMID: 11371646. Lee C, Yen K, Cohen P. Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol Metab. 2013;24(5):222-228. PubMed PMID: 23497723. Zempo H, Kim SJ, Fuku N, et al. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c. Aging (Albany NY). 2021;13(2):1692-1717. PubMed PMID: 33476289.

For laboratory research only. Not for human or veterinary use, diagnosis, treatment, cure, or prevention of any disease. THIS PRODUCT IS NOT FOR HUMAN CONSUMPTION.