Humanin
HN · MT-RNR2 peptide · HNG · S14G-Humanin · Humanin-G
First mitochondrial-derived peptide discovered, studied for cytoprotection and metabolism.
Typical dose
1 mg
3x per week
Range
0.5–2
mg
Half-life
—
see Dosing
Evidence
Animal only
Subcutaneous
What it is
Humanin is a 24-amino-acid peptide encoded within the mitochondrial 16S rRNA gene, identified in 2001 in the surviving neurons of an Alzheimer's brain — hence the name. It was the first mitochondrial-derived peptide found, and it opened the field that MOTS-c and the SHLP peptides later joined.
Its core biology is cytoprotection. Humanin blocks apoptosis triggered by a wide range of insults, and circulating levels fall with age in humans while being notably high in centenarians and their offspring and in long-lived mutant mice. In animals it improves insulin sensitivity, protects cardiac tissue from ischaemic injury, and preserves cognition in Alzheimer's models.
Two practical points. First, most published research uses HNG (S14G-Humanin), an analogue with a single serine-to-glycine swap at position 14 that is far more potent than the native sequence — what is sold as "humanin" may be either, and the dose implications differ. Second, there has never been a human trial of injected humanin or HNG, so all dosing is extrapolation.
How it works
Humanin works from outside the cell as well as inside it. Secreted humanin binds a trimeric receptor complex (CNTFR/WSX-1/gp130) and signals through STAT3, and it also acts intracellularly by binding pro-apoptotic Bax and BimEL and preventing them from permeabilising the mitochondrial membrane. The net effect is a cell that survives stress it would otherwise die from.
Metabolically it raises insulin sensitivity partly through a hypothalamic route, and it interacts with the IGF-1 axis — humanin binds IGFBP-3, which both prolongs its own circulation and shifts IGF-1 availability. That IGFBP-3 interaction is why measured half-life varies so much between studies and between analogues.
Dosing
These figures assume the HNG analogue, which is what almost all research uses and what most vendors ship. Native humanin is markedly less potent, so a product confirmed as native sequence is usually run at the top of this range or above. Confirm which one you have before setting a dose.
Reconstitution calculator
Pre-loaded with Humanin’s vial size, water volume and typical dose. Change anything.
Typical: 1 mg · range 0.5–2
Draw to
40 u
0.4 mL · 1 mg
Concentration
2.5 mg/mL
25 mcg per unit
Doses per vial
5
Vial lasts
12 days
Draw to 40 units on the barrel.
Once mixed
Refrigerate at 2-8 C, protect from light, and use within 2-3 weeks — shorter than most peptides because of oxidation risk at the cysteine.
2 mL of bacteriostatic water into a 5 mg vial gives 2.5 mg/mL, so a 1 mg dose is 0.4 mL (40 units); into a 10 mg vial the same 2 mL gives 5 mg/mL and 1 mg is 0.2 mL (20 units). Humanin contains a cysteine and is prone to oxidation and aggregation — add the water slowly down the wall, swirl rather than shake, and keep it out of light.
Storage
Before mixing
Refrigerated at 2-8 C the sealed powder holds for 12-24 months; -20 C is preferable for long storage given the free cysteine.
After mixing
Refrigerate at 2-8 C, protect from light, and use within 2-3 weeks — shorter than most peptides because of oxidation risk at the cysteine.
Reported benefits
- ▪Blocks apoptosis from a broad range of cellular insults
- ▪Improved insulin sensitivity and glucose handling in rodent models
- ▪Cardioprotective against ischaemia-reperfusion injury in animals
- ▪Preserved cognition and reduced amyloid toxicity in Alzheimer's models
- ▪Circulating levels track healthy longevity in humans and are elevated in centenarian offspring
- ▪Protected retinal and endothelial cells from oxidative stress in vitro
Side effects
- ▪No human safety data exists — the side-effect profile is genuinely unknown, not merely benign
- ▪Injection-site redness or irritation in anecdotal reports
- ▪Possible additive glucose lowering with insulin, metformin or a GLP-1
- ▪Interaction with the IGF-1/IGFBP-3 axis of uncertain consequence during long use
- ▪Theoretical concern that a broad anti-apoptotic signal could help abnormal cells survive as well as healthy ones
- ▪Product identity risk: native humanin and HNG are sold interchangeably and are not equipotent
Do not use if
- ▪Active or recently treated malignancy, on the anti-apoptotic argument
- ▪Pregnancy and breastfeeding — no data
- ▪Use alongside insulin or sulfonylureas without glucose monitoring
- ▪Known hypersensitivity to the peptide or to benzyl alcohol in bacteriostatic water
Evidence level — Animal only
Preclinical animal data — no meaningful human trials.
Not FDA-approved for any indication; sold as a research chemical in most markets.
Commonly run with
MOTS-c
Mitochondrial-encoded peptide studied for insulin sensitivity and exercise capacity.
5 mg · 3x per week
SS-31
Cardiolipin-binding mitochondrial peptide, FDA-approved as elamipretide for Barth syndrome.
10 mg · Once daily
Epitalon
Pineal-derived tetrapeptide studied for telomerase activation and circadian regulation.
10 mg · Once daily during a course
Humanin FAQ
What is the difference between humanin and HNG?+
HNG is humanin with serine at position 14 replaced by glycine. That single change makes it dramatically more potent and more stable, which is why nearly all published research uses it. Vendors often label HNG simply as humanin, so ask for the sequence or a certificate of analysis before dosing.
Is there any human evidence at all?+
Only observational. Human studies have measured naturally circulating humanin and correlated higher levels with longevity, better insulin sensitivity and slower cognitive decline. Nobody has injected it into humans in a published trial, so causation in people is unestablished.
Does it do anything for training or body composition?+
Nothing directly. It is not anabolic, does not raise GH or IGF-1 output, and has no appetite effect. The interest is metabolic and cytoprotective, so it belongs in a longevity stack rather than a performance one.
Why is the recommended storage time shorter than other peptides?+
The sequence contains a free cysteine, which oxidises and can drive disulfide-linked aggregation in solution. Keeping the reconstituted vial cold, dark and used within two to three weeks limits how much of the peptide degrades before you inject it.
References
- 1.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 of the United States of America (2001) PMID 11371646
- 2.Humanin: a novel central regulator of peripheral insulin action — PLoS One (2009) PMID 19623253
- 3.The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan — Aging (Albany NY) (2020) PMID 32575074
- 4.Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers — Aging (Albany NY) (2016) PMID 27070352
More longevity & mitochondrial
Epitalon
Pineal-derived tetrapeptide studied for telomerase activation and circadian regulation.
10 mg · Once daily during a course
MOTS-c
Mitochondrial-encoded peptide studied for insulin sensitivity and exercise capacity.
5 mg · 3x per week
SS-31
Cardiolipin-binding mitochondrial peptide, FDA-approved as elamipretide for Barth syndrome.
10 mg · Once daily