Humanin 10mg – Research Grade Mitochondrial Peptide

Humanin is a 24-amino-acid peptide encoded within the mitochondrial 16S ribosomal RNA gene and is the founding member of the mitochondrial-derived peptide (MDP) family. The peptide was identified in 2001 by Hashimoto and colleagues in Japan in a cDNA expression-screening project searching for factors that protected cultured neuronal cells from amyloid-β-induced toxicity. The screen recovered a transcript encoding a 24-residue peptide that, when expressed or applied exogenously, protected the cells. The transcript turned out to be encoded within a mitochondrial ribosomal RNA gene — a previously unrecognized class of small open reading frames embedded in mitochondrial DNA — and the peptide was named "humanin" by the discovering group.

The recognition that the human mitochondrial genome encodes short biologically active peptides beyond the canonical 13 oxidative-phosphorylation subunits opened an entire field of mitochondrial-derived peptide research. Humanin was followed by the identification of MOTS-c (in 2015, by Pinchas Cohen and Changhan Lee's group), the SHLP family (small humanin-like peptides 1-6, also from the Cohen group), and additional MDPs. The MDP family is now recognized as a distinct class of mitochondrial-encoded signaling peptides with roles in cell survival, metabolism, and intercellular signaling.

The published humanin research literature includes work on its cytoprotective effects in cultured neurons, cardiomyocytes, and beta-cells; on its receptor pharmacology (a heterotrimeric receptor complex involving FPRL1, CNTFR, and WSX-1); on its modulation of apoptotic pathways (notably interaction with the BH3-only protein Bax); and on its potential roles in aging, metabolism, neurodegenerative disease, and ischemic injury.

This page is a research-only educational reference. Humanin supplied as a research peptide is intended for laboratory and analytical work; no therapeutic or human-use claims are made.

Humanin is a 24-amino-acid peptide with the sequence MAPRGFSCLLLLTSEIDLPVKRRA. The peptide is encoded within the mitochondrial 16S rRNA gene at a small open reading frame that is translated either by the mitochondrial ribosome (with a methionine start codon) or, according to some published evidence, by cytoplasmic ribosomes after transcript export. The translated product is then either retained in the mitochondrial compartment or secreted into the extracellular space, where it acts as a paracrine and endocrine signaling peptide.

The biological activity of humanin centers on cell-survival promotion. Exogenous humanin protects cultured cells from a range of cytotoxic stimuli, including amyloid-β (the original Alzheimer-research context), oxidative stress, serum withdrawal, ischemic insult, and various pro-apoptotic stimuli. The mechanism appears to involve both extracellular signaling through the heterotrimeric humanin receptor complex (which initiates STAT3-mediated transcriptional cytoprotection) and direct intracellular interaction with components of the intrinsic apoptotic pathway (humanin has been shown to bind and sequester the BH3-only protein Bax, blocking its translocation to mitochondria and the initiation of intrinsic apoptosis).

Several humanin analogs have been characterized in research, generated by amino-acid substitution to modulate stability, receptor binding, or specific activities. Common analogs include S14G-humanin (HNG, with the serine at position 14 replaced by glycine; substantially more potent than native humanin in cell-survival assays) and various other engineered variants. Synthetic native humanin and HNG are the two most common forms used in published research.

It is important to be clear about what humanin is not. It is not a hormone in the classical pituitary/endocrine sense, although it has circulating concentrations and endocrine-like signaling. It is not an approved medicine in any major jurisdiction. And it is not a "longevity drug" — its biological role in aging is an active research question with published animal-model and human-cohort data but not a clinical indication.

The discovery of humanin in 2001 came from a screen designed to identify novel cytoprotective factors. Yuichi Hashimoto and colleagues in the laboratory of Ikuo Nishimoto at Keio University screened a brain cDNA library for transcripts that, when overexpressed in a neuronal cell line, protected the cells from amyloid-β-induced toxicity. One recovered transcript encoded a 24-residue peptide that protected the cells in subsequent validation experiments. The transcript was mapped to a small open reading frame within the mitochondrial 16S rRNA gene — an unconventional location that initially raised significant questions about authenticity and translation mechanism.

Subsequent work over the following decade established the basic biology of humanin: the peptide is generated from a mitochondrial-encoded transcript (with some evidence for both mitoribosomal and cytoplasmic translation), it is detectable in plasma and tissues at picomolar to low-nanomolar concentrations, its concentration declines with age in published human studies, and it has cytoprotective activity in a wide range of cell-culture and animal-model systems.

The receptor pharmacology was elucidated through the 2000s. Humanin was shown to bind a heterotrimeric receptor complex composed of formyl peptide receptor-like 1 (FPRL1, also called FPR2), ciliary neurotrophic factor receptor (CNTFR), and WSX-1 (IL-27 receptor alpha subunit). The receptor complex activates STAT3 signaling and transcriptionally upregulates cytoprotective gene programs. The intracellular Bax-binding activity was characterized separately and provides a non-receptor-dependent mechanism for direct interference with the intrinsic apoptotic pathway.

The 2010s saw the broader MDP family emerge. Pinchas Cohen's group at USC, working with Changhan Lee, identified MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) in 2015 as a second mitochondrial-encoded peptide with substantial biological activity, particularly in metabolism. The same group identified the SHLP family (small humanin-like peptides 1-6) encoded at additional mitochondrial loci. By the late 2010s, the mitochondrial-derived peptide family was recognized as a distinct class of mitochondrial-encoded signaling peptides with implications for aging, metabolism, and neurodegenerative disease.

Humanin has been investigated in published human-cohort studies showing age-related decline in circulating humanin and association of higher humanin levels with healthier aging markers. It has been studied in animal models of Alzheimer's disease, type 2 diabetes, atherosclerosis, ischemic injury, and other conditions. No humanin-based therapy has been approved in any major jurisdiction; the molecule is studied as a research peptide and as a biomarker of mitochondrial status in aging research.

The humanin receptor system is unusual in being heterotrimeric. The three components — FPRL1/FPR2, CNTFR, and WSX-1 — each contribute to ligand binding and downstream signaling, but none alone constitutes a high-affinity humanin receptor. The trimeric receptor architecture is one of the distinctive features of humanin pharmacology and contributes to the complexity of dissecting receptor-mediated versus intracellular effects in research models.

Downstream of receptor engagement, the canonical signaling output is STAT3 activation. STAT3 is a JAK-coupled transcription factor that, in the cytoprotective context, drives transcription of anti-apoptotic genes (Bcl-2, Bcl-xL) and survival-pathway components. The receptor complex also engages ERK/MAPK signaling in some published contexts. The transcriptional output is the principal mechanism by which extracellular humanin produces cytoprotection over the time scale of hours.

Separately, intracellular humanin binds and sequesters the BH3-only protein Bax. Bax is a critical effector of intrinsic apoptosis — under apoptotic stimuli, Bax translocates from the cytoplasm to the outer mitochondrial membrane, oligomerizes, and forms pores that release cytochrome c and trigger the apoptotic cascade. Humanin binding to Bax in the cytoplasm blocks this translocation and provides a more rapid, transcription-independent cytoprotective mechanism. The dual mechanism — receptor-mediated transcriptional cytoprotection plus intracellular Bax sequestration — explains the robustness of humanin's cytoprotective effects across diverse cell systems and stimuli.

In the broader MDP family context, humanin shares a thematic role with MOTS-c and the SHLPs as mitochondrial-encoded signaling peptides whose levels and signaling activity convey information about mitochondrial status to the rest of the cell and organism. The "mitokine" concept — that mitochondria signal their functional state via secreted peptide signals — is one of the emerging frameworks in the field. Humanin's age-related decline in circulating concentration is consistent with this framing and provides a mechanistic candidate for the broader phenomenon of age-related mitochondrial dysfunction and its systemic consequences.

In neuronal cytoprotection research, humanin protects cultured neurons from amyloid-β toxicity (the original discovery context), from prion-protein toxicity, from oxidative-stress-induced apoptosis, and from various other insults. In cardiac research, humanin protects cardiomyocytes from ischemia-reperfusion injury and improves outcomes in rodent ischemic-injury models. In pancreatic beta-cell research, humanin protects against gluco- and lipotoxicity. In atherosclerosis research, humanin levels are inversely associated with plaque burden in some human-cohort studies. The breadth of cytoprotective contexts is consistent with the receptor-mediated transcriptional program plus intracellular Bax sequestration acting through pathways shared across many cell types.

Humanin is a 24-amino-acid peptide with the sequence MAPRGFSCLLLLTSEIDLPVKRRA. The molecular weight is approximately 2.7 kDa. The peptide contains a single cysteine residue at position 8 that contributes to the formation of homodimers in some preparations (a feature relevant to handling and assay use). The peptide has an amphipathic character with a central hydrophobic core that contributes to its membrane interactions.

Several humanin analogs have been characterized in research. S14G-humanin (HNG), with serine at position 14 replaced by glycine, is reported in published research to be approximately 1000-fold more potent than native humanin in some cytoprotective assays. F6A-humanin (with the phenylalanine at position 6 replaced by alanine) lacks intracellular Bax-binding activity and is used as a research tool to isolate receptor-mediated effects. Various other substitutions have been used to dissect structure-activity relationships and to engineer molecules with selective properties.

Research-grade humanin is produced by standard solid-phase peptide synthesis (SPPS), purified by reversed-phase HPLC to ≥98% purity, and verified by analytical HPLC and mass spectrometry. The peptide is supplied as a lyophilized powder and reconstituted in sterile aqueous buffer (sometimes with a small fraction of organic solvent for solubility) for laboratory use. The cysteine residue requires attention to redox conditions during handling to control dimerization.

In published research, humanin has been used in several principal applications:

Neuronal cytoprotection. Cultured neurons (primary and immortalized) are treated with humanin or HNG to investigate protection from amyloid-β, oxidative stress, serum withdrawal, and other neurotoxic insults. This is the original discovery context and remains an active research area in Alzheimer-disease and broader neurodegeneration research.

Cardiac ischemia-reperfusion. Ex-vivo and in-vivo rodent cardiac ischemia-reperfusion models have been used to investigate humanin and HNG cardioprotection. Published research reports reduced infarct size, improved cardiac function, and reduced apoptotic cardiomyocyte loss with humanin treatment in these models.

Pancreatic beta-cell research. Cultured beta-cells and rodent diabetes models are studied with humanin to investigate beta-cell protection against gluco- and lipotoxicity. The literature includes work on humanin effects on insulin secretion and beta-cell survival in diabetes-relevant contexts.

Atherosclerosis. Humanin levels have been measured in human cohorts in relation to atherosclerotic-disease burden, and animal-model studies have investigated humanin effects on lesion development.

Aging biomarker research. Circulating humanin levels decline with age in published human-cohort studies. The relationship between humanin levels and aging-associated phenotypes (cognitive function, metabolic status, cardiovascular health) is an active research area in the broader MDP-and-aging literature.

Receptor pharmacology. The heterotrimeric FPRL1/CNTFR/WSX-1 receptor complex is studied in heterologous expression systems and native cells using humanin and analogs as ligands, often in comparison with analogs that retain or lack specific activities (e.g., F6A-humanin to dissect receptor versus Bax-binding effects).

All applications are research-context. Nothing on this page describes a clinical protocol, dose, or therapy for human use.

Humanin is the founding member of the mitochondrial-derived peptide (MDP) family.

Humanin is a 24-amino-acid peptide encoded within the human mitochondrial 16S ribosomal RNA gene and the founding member of the mitochondrial-derived peptide (MDP) family. Identified in 2001 by Hashimoto and colleagues in a screen for amyloid-β-cytoprotective factors, humanin has cytoprotective activity across many cell types via two convergent mechanisms: extracellular signaling through a heterotrimeric FPRL1/CNTFR/WSX-1 receptor complex (STAT3-mediated transcriptional cytoprotection) and direct intracellular binding to the apoptotic effector Bax (blocking its mitochondrial translocation).

In published research, humanin and its more potent analog HNG (S14G-humanin) are used to investigate cytoprotection in neuronal, cardiac, beta-cell, and other systems; in animal models of Alzheimer's disease, cardiac ischemia-reperfusion, and metabolic disease; and as a biomarker of mitochondrial status in human aging cohorts where circulating humanin levels decline with age. The molecule sits within the broader MDP family alongside MOTS-c and the SHLP peptides as a representative of mitochondrial-encoded peptide signaling.

This page is research educational only. Humanin supplied as a research peptide is intended for laboratory and analytical work; no therapeutic or human-use claims are made.