What is the difference between humanin and MOTS-c?

Both are mitochondrial-derived peptides, but they have different functions. Humanin is primarily cytoprotective and anti-apoptotic, while MOTS-c primarily affects metabolism and exercise physiology. They may work synergistically in anti-ageing research.

Do humanin levels change with age?

Yes. Circulating humanin levels decline significantly with age. Studies show lower levels in older adults and in patients with age-related diseases. Children of centenarians tend to have higher humanin levels, suggesting a link to longevity.

Can you increase humanin levels naturally?

Research suggests exercise may increase humanin levels, though data is limited. Mitochondrial health through exercise, caloric restriction, and avoiding mitochondrial toxins may support endogenous humanin production.

Is HNG the same as humanin?

HNG (S14G-Humanin) is a synthetic analogue of humanin with a single amino acid substitution that makes it approximately 1,000-fold more potent. It is used extensively in research but is not a natural peptide.

Fact-checked by the Peptide Authority Editorial Board · Last reviewed: 8 March 2026

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Longevity & Anti-Ageing•Updated 2026-03-08•5 min read

What Is Humanin? Benefits, Research & Safety

A mitochondrial-derived peptide with cytoprotective and anti-apoptotic properties, researched for neuroprotection, metabolic regulation, and ageing.

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Also known as:

Humanin Peptide

MT-RNR2

DAnimal/cell evidence onlyUK: Sold as 'research only' (UK)WADA: Sport status unclear

UK summary: Not a licensed UK medicine. Mitochondrial-derived peptide investigated for neuroprotection and longevity. All studies are preclinical or small observational; no human therapeutic use.

Quick Facts

Overview

Humanin (HN) is a 24-amino acid peptide encoded by the mitochondrial genome (MT-RNR2 gene within the 16S rRNA region). It was discovered in 2001 as a factor that protected neurons from Alzheimer's disease-related toxicity, making it one of the first identified mitochondrial-derived peptides (MDPs). Humanin belongs to the same family as MOTS-c, both being peptides encoded within the mitochondrial genome rather than the nuclear genome. This discovery challenged the long-held assumption that mitochondrial DNA only encodes proteins involved in oxidative phosphorylation. The peptide exerts potent cytoprotective effects through multiple mechanisms, including inhibition of apoptosis (programmed cell death), reduction of oxidative stress, and modulation of inflammatory pathways. Humanin levels decline with age, leading researchers to hypothesise that it plays a role in the ageing process. Research interest in humanin spans neurodegenerative diseases (Alzheimer's, Parkinson's), metabolic conditions (insulin sensitivity, diabetes), cardiovascular protection, and general anti-ageing applications. Several synthetic analogues with enhanced potency have been developed, including HNG (S14G-Humanin), which is approximately 1,000-fold more potent than native humanin. Humanin is not approved for human therapeutic use and remains a research compound. All information is for educational purposes.

Evidence standards summary

Humanin — evidence and risk at a glance

Twenty standard modules scored against the Peptide Authority evidence grading methodology. Missing modules indicate the field has not yet been characterised editorially — treat absences as uncertainty rather than reassurance.

01Evidence snapshot

DAnimal/cell evidence onlyOverall grade against our evidence grading methodology.

Not a licensed UK medicine. Mitochondrial-derived peptide investigated for neuroprotection and longevity. All studies are preclinical or small observational; no human therapeutic use.

02Human evidence grade

ETheoretical / insufficientStrength of evidence from published human trials.

03Preclinical evidence grade

CLimited human evidenceAnimal-model and in-vitro evidence quality.

04Regulatory status

UK: Not licensed for any indication. Research compound only.
EU: Not approved for human use.
Notes: Humanin is a research peptide with no regulatory approvals anywhere. All studies are preclinical or observational. Products available are from research chemical suppliers and not intended for human use.

05Approved medical uses

None in the UK or EU as a finished medicine. (Or: not yet documented; treat as absence rather than approval.)

06Unapproved / promotional claims

Reverses Alzheimer's disease.
Extends human lifespan.
Treats long COVID and chronic fatigue.
Restores mitochondrial function in healthy adults.

07Common internet claims

Marketed in longevity stacks alongside MOTS-c and SS-31.
Sold by online retailers as research-only injectable.
Promoted on biohacker podcasts for mitochondrial health.

08Claim vs evidence

Claim	Evidence	Human evidence?	Regulatory concern	Safer wording
“Protects against Alzheimer's”	D	No	High	Preclinical neuroprotective effects against amyloid toxicity; no human RCT data.
“Extends lifespan”	E	No	High	Animal-model longevity claims; no human evidence.

09Safety uncertainty score

High

Limited human safety data; meaningful uncertainty about rare or long-term effects.

10Known adverse signals

Essentially no human safety data.
Injection-site reactions reported anecdotally.
Unknown chronic effects of supraphysiological humanin signalling.
Theoretical interactions with apoptosis-related drugs (chemotherapy).

11Drug-interaction uncertainty

High

Interaction picture sparse; meaningful uncertainty when combined with other medicines.

12Anti-doping status

WADA: Sport status unclearWADA strict-liability framing applies.

13UK legal position

UK: Sold as 'research only' (UK)

Not licensed for any indication. Research compound only.

Read the full UK legal guide → Research peptides and UK law

14EU legal position

Not approved for human use.

15What this page cannot tell you

Whether a UK-purchased vial contains humanin at the labelled concentration.
Whether the preclinical neuroprotection translates to human Alzheimer's prevention.
Long-term consequences of exogenous mitochondrial-derived peptide signalling.
Whether it interferes with apoptosis pathways relevant to cancer surveillance.

16Last reviewed

Last reviewed: 8 March 2026

Next review due: 8 March 2027

Spotted an error or something out of date? Send a correction.

17Citation quality score

CLimited human evidenceQuality of the sources we cite, graded against the evidence grading methodology.

18Research gaps

No registered Phase 1 trials in humans for any indication.
Pharmacokinetic data in humans absent.
Long-term safety unstudied.

19Safer alternatives / established care pathways

Evidence-based longevity interventions: exercise, sleep, Mediterranean diet, smoking cessation.
NHS memory clinic referral for genuine cognitive concerns; licensed Alzheimer's medications under specialist care.
Routine cancer-screening uptake — the highest-impact longevity intervention available.

20Doctor discussion prompts

Questions to ask a qualified clinician

These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

Is Humanin a licensed UK medicine?
What licensed treatments exist for the cognitive / longevity concern I'm raising?

Discovery & History

Humanin was discovered in 2001 by Yuichi Hashimoto and colleagues at the National Institute for Longevity Sciences in Japan. They used a functional expression screening approach to identify factors that could protect neurons from toxicity induced by familial Alzheimer's disease mutant proteins. The surprising finding was that this protective factor was encoded by the mitochondrial genome—an unprecedented discovery that expanded understanding of mitochondrial biology. The peptide was named "humanin" for its potential to benefit human health. Subsequent research revealed that humanin circulated in blood and cerebrospinal fluid, suggesting endocrine-like functions. Studies showed that circulating humanin levels correlated inversely with age and various age-related diseases. The discovery of humanin, along with MOTS-c (identified in 2015), established the concept of mitochondrial-derived peptides as a new class of signaling molecules with systemic effects on metabolism, stress responses, and ageing. Synthetic analogues, particularly HNG (with a serine-to-glycine substitution at position 14), were developed to enhance potency and stability for research applications.

Mechanism of Action

Humanin exerts cytoprotective effects through several pathways: **Anti-Apoptotic Signaling** Humanin inhibits programmed cell death: - Binds to and inhibits Bax (pro-apoptotic protein), preventing mitochondrial membrane permeabilization - Interacts with IGFBP-3, blocking its pro-apoptotic effects - Prevents cytochrome c release from mitochondria - Inhibits caspase activation cascade **STAT3 Pathway Activation** Humanin signals through a trimeric receptor complex: - Binds to CNTFR/WSX-1/gp130 receptor complex - Activates JAK/STAT3 signaling - Promotes cell survival gene expression - Enhances neuroprotective pathways **FPRL1/FPRL2 Receptor Activation** Alternative signaling pathway: - Activates formyl peptide receptor-like receptors - Triggers ERK1/2 signaling - Promotes anti-inflammatory responses **Metabolic Effects** Humanin influences metabolism: - Enhances insulin sensitivity through STAT3 - Reduces hepatic glucose production - Modulates IGF-1/insulin signaling axis - Interacts with IGFBP-3 to regulate growth factor availability

Researched Benefits

Based on preclinical and clinical research findings:

1
Neuroprotection against Alzheimer's-related toxicity
2
Anti-apoptotic effects in multiple cell types
3
Enhanced insulin sensitivity in animal models
4
Cardiovascular protection (reduced atherosclerosis in mice)
5
Reduced oxidative stress and mitochondrial dysfunction
6
Potential anti-ageing effects (correlates with longevity)
7
Protection against ischaemia-reperfusion injury

Claim vs Evidence

How popular claims about Humanin stack up against the current research, graded using our public evidence grading methodology.

Claim	Evidence	Human evidence?	Regulatory concern	Safer wording
“Protects against Alzheimer's”	D	No	High	Preclinical neuroprotective effects against amyloid toxicity; no human RCT data.
“Extends lifespan”	E	No	High	Animal-model longevity claims; no human evidence.

Theoretical Dosing & Protocols

⚠️ Educational Only: The following information is derived from research literature and is not a prescription or recommendation. No standardised human dosing exists. Always consult a qualified healthcare professional.

Theoretical Dosage	Research only; no established human dosing
Frequency	Variable in preclinical studies
Duration	Research protocols vary
Notes	Humanin and its analogues (HNG) are research compounds only. No human clinical trials for therapeutic use have been completed. Most data comes from cell culture and animal studies. Not available as a pharmaceutical product.

Administration Routes

Routes studied in research settings (educational only):

Intraperitoneal injection (animal studies)
Intravenous (preclinical research)
Intranasal (experimental)

Half-Life	Stability
Short in circulation; synthetic analogues have improved stability	Native humanin has limited stability; lyophilised powder stored at -20°C

Safety Profile & Known Risks

Commonly Reported Side Effects

Limited human data available
Generally well tolerated in animal studies

Rare Risks & Concerns

Unknown long-term effects in humans
Theoretical concerns about anti-apoptotic effects on tumour cells
Insufficient safety data for human use

Contraindications

Not approved for human use
Active malignancy (theoretical concern due to anti-apoptotic mechanism)
Pregnancy and breastfeeding

UK & EU Regulatory Context

🇬🇧 United Kingdom

Not licensed for any indication. Research compound only.

🇪🇺 European Union

Not approved for human use.

Humanin is a research peptide with no regulatory approvals anywhere. All studies are preclinical or observational. Products available are from research chemical suppliers and not intended for human use.

Clinical Studies Summary

Redox-sensitive miRNAs and Humanin could mediate effects of exercise and astaxanthin on oxidative stress and inflammation in type 2 diabetes.

This study was also registered in Iranian Registry of Clinical Trials (IRCT20230225057524N1). Consent for publication: Not applicable.

Sci Rep. 2025View on PubMed

Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer's disease.

Findings suggest that the cognitive benefits of exercise could be mediated by the upregulation of neuroprotective factors in NDEVs. Additionally, our results indicate that AD subjects carrying APOE ε4 are more responsive to the neuroprotective effects of physical activity.

Alzheimers Res Ther. 2023View on PubMed

Mitochondria‑derived peptides: Promising microproteins in cardiovascular diseases (Review).

It is necessary to improve drug delivery systems to enhance the bioavailability of MDPs. Moreover, integrating basic research with clinical trials is essential to bridge the gap between experimental findings and clinical applications.

Mol Med Rep. 2025View on PubMed

Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases.

Ethical Approval: Not applicable. Informed Consent: Not applicable.

Mol Neurobiol. 2025View on PubMed

Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities.

We also provide insights into the current advancements in clinical research related to the utilization of MDPs in the treatment of CVDs. This review may provide valuable information with MDPs for CVD diagnosis and treatment.

J Adv Res. 2024View on PubMed

Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives.

MDPs attenuate disease pathology including Type 1 diabetes (T1D), Type 2 diabetes (T2D), gestational diabetes, Alzheimer's disease (AD), cardiovascular diseases, prostate cancer, and macular degeneration. The current review will focus on the MDP regulation of T2D, T1D, and gestational diabetes along with an emphasis on the evolutionary pressures for conservation of the amino acid sequences of MDPs.

Peptides. 2024View on PubMed

Registered Trials & Regulatory Status

Registered trials

Currently recruiting

Furthest phase

none

Approved product

1 of 1 completed trials have never posted results. Unreported trials are not neutral: results that go unpublished are more often negative ones.

Comparison of the Effects of General Anesthesia and Combined Spinal-Epidural Anesthesia on Ferroptosis, Humanin and MOTS-c Levels in Renal Transplantation

Status: Recruiting · 68 participants · University of Gaziantep

Conditions: Kidney Disease, End-Stage, Kidney Transplant, Kidney

No results postedNCT07678073

Clinical Value of Plasma Humanin in Acute Kidney Injury

N/A

Status: Unknown · 60 participants · Guangdong Provincial People's Hospital

Conditions: Acute Kidney Injury

No results postedNCT06105229

Humanin Isoforms in Cardiac Muscle and Blood Plasma and Major Complications After Cardiac Operation

N/A

Status: Completed · 106 participants · University of Tartu

Conditions: Myocardial Ischemia, Coronary Artery Bypass Surgery

No results postedNCT03431844

Adverse event reports (FDA FAERS)

Not applicable: no licensed product contains this peptide, so it is not reported through FAERS. This is an absence of surveillance, not evidence of safety.

Source: ClinicalTrials.gov and openFDA. Updated automatically.

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Frequently Asked Questions

Questions to ask a qualified clinician about Humanin