Humanin

Origin and structure

Humanin was discovered in 2001 by Yuichi Hashimoto, Ikuo Nishimoto and colleagues at Keio University School of Medicine in Tokyo. They put a library of genes from the occipital cortex of a patient with Alzheimer's disease into nerve-derived cells that died when they expressed a mutant Alzheimer's gene, and kept the genes that let cells survive. The protective stretch was a 75-base reading frame coding for a 24-amino-acid peptide, MAPRGFSCLLLLTSEIDLPVKRRA, which they named humanin.

In 2003 other laboratories found the same peptide independently, as a partner of IGFBP-3, one of the proteins that carry IGF-1 in the blood, and as a peptide that binds Bax, a protein that triggers cell death. The Bax group pointed out that an identical reading frame sits in mitochondrial DNA; it lies in the gene for the 16S ribosomal RNA. That makes humanin one of the mitochondrial-derived peptides, a family that also includes MOTS-c. The same group suggested that the sequence arose in mitochondria and was later copied into the nuclear genome.

How it is thought to work

Inside the cell, humanin binds Bax, a protein that sets off programmed cell death (apoptosis), and keeps it from moving to the mitochondria, where Bax would release the signals that kill the cell. It also binds IGFBP-3.

Outside the cell, humanin acts on receptors on the cell surface: a three-part receptor (CNTFR, WSX-1 and gp130) related to the interleukin-6 receptor, and the formyl-peptide receptor FPRL1. These switch on survival pathways such as STAT3, AKT and ERK. In rats, humanin infused into the brain improved the body's insulin sensitivity, and the effect on the liver depended on STAT3 signalling in the hypothalamus, which suggests that part of its metabolic action runs through the brain.

Most of these mechanisms were worked out in cell cultures, and several of the animal studies used more potent synthetic analogues such as HNG rather than humanin itself. Whether the body's own humanin, at the levels found in blood, does the same is not established.

Is humanin approved?

No. Humanin is not an authorised medicine in the EU, the Netherlands or the US, and no registered clinical trial has given it to people.

In the Netherlands the medicines register of the CBG (Geneesmiddeleninformatiebank), which also lists the medicines authorised EU-wide, contains no product with humanin. It may therefore not be sold, advertised or supplied as a medicine or for use in people. Humanin offered online is research material, not a medicine.

• EU and the Netherlands: no marketing authorisation; no product in the Dutch medicines register (checked 28 October 2026).
• US: not approved by the FDA. Humanin does not appear in any of the three categories of bulk substances nominated for pharmacy compounding under section 503A (FDA list updated 14 May 2026).
• Sport: WADA does not name humanin, but class S0 prohibits at all times any pharmacological substance with no approval for human therapeutic use. According to USADA, the 2027 list, in force from 1 January 2027, names peptides in general in S0.

What the research shows

Almost all of the research is in cells and animals. In people, humanin has only been measured, in blood, spinal fluid or tissue: ClinicalTrials.gov lists seven studies that mention it (checked 28 October 2026), and none gives humanin or an analogue to participants. The main findings:

• Alzheimer's models (cells and mice): humanin protected nerve-derived cells against damage from familial Alzheimer's genes and amyloid-beta, and HNG injected into the brain prevented amyloid-induced memory loss in mice.
• Metabolism (rats): humanin infused into the brain improved insulin sensitivity, and a single dose of a potent analogue lowered blood glucose in Zucker diabetic fatty rats.
• Ageing (worms and mice): worms engineered to make extra humanin lived slightly longer on average, 19.0 against 17.7 days. In 100 female mice treated with HNG from 18 months of age for 14 months, lifespan did not increase, although the treated mice were lighter, carried less visceral fat and had lower inflammatory markers. Aged mice in the same programme did better on a balance test (23 and 24 mice per group) and on memory tests in smaller subgroups of 7 or 8 mice.
• Blood levels and age (people): a 2009 study reported lower levels in older people, but in 693 people aged 21 to 113 levels rose with age and were highest in centenarians, and higher levels of these stress-related molecules, humanin among them, went with worse health markers in 70-year-olds. In another study, 18 children of centenarians had higher levels than 19 controls.
• Disease (people): in a very small comparison, 4 people with Alzheimer's disease had less humanin in their spinal fluid than 3 controls. A common genetic variant at the end of the humanin reading frame, linked to 14% lower blood levels, went with faster cognitive ageing in 10,158 participants of the US Health and Retirement Study.
• Cancer (mice): in a model of triple-negative breast cancer, humanin given to the mice sped up tumour growth and lung metastases and weakened chemotherapy.

Humanin, HNG and MOTS-c

HNG, also written S14G-humanin, is humanin with one change: glycine instead of serine at position 14. In cell tests it protects at concentrations about 1,000 times lower than native humanin. Several of the animal studies above used HNG or other analogues rather than humanin itself, so results for one cannot simply be carried over to the other. Neither has been tested in people.

MOTS-c is a separate mitochondrial-derived peptide, coded in the gene for the 12S rather than the 16S ribosomal RNA. Unlike humanin, it is named on the WADA Prohibited List, as a metabolic modulator in class S4.4.1.

Safety: what is and is not known

There are no human safety data. Humanin and HNG have never been given to people in a registered or published trial, so nothing is known about side effects in humans, about repeated exposure, or about interactions with medicines.

The concern raised most often follows from how humanin works: a peptide that keeps cells from dying might also keep cancer cells alive. That is not only a theory. In the 2020 breast-cancer mouse study, humanin made tumours grow faster and spread more and weakened chemotherapy, and the same group found more humanin in triple-negative breast-cancer biopsies than in healthy breast tissue. Other researchers have studied humanin analogues for the opposite purpose, to shield healthy tissue during chemotherapy, so the animal evidence on cancer is mixed and unresolved.

Frequently asked questions

Has humanin been tested in humans?

Not as a treatment. Every human study so far measures the body's own humanin, in blood, spinal fluid or heart tissue, and relates it to age or disease. ClinicalTrials.gov lists seven such studies (checked 28 October 2026), none of which gives humanin or an analogue to participants, and no published trial has done so either. Its effects and safety in people are therefore unknown.

Is humanin legal in the Netherlands?

Humanin is not a registered medicine in the Netherlands: the Dutch medicines register, which also lists EU-wide authorisations, contains no product with it. It may therefore not be sold, advertised or supplied for use in people. Trading it as research material is a different status, which our guide on research-use-only products in the Netherlands explains. For athletes it is prohibited however it was obtained.

Is humanin banned in sport?

Not by name, but it falls under WADA class S0, which prohibits at all times any pharmacological substance that no health authority has approved for human therapeutic use. The US anti-doping agency USADA warns that a peptide not named on the list may still be prohibited, and says the 2027 list, in force from 1 January 2027, names peptides in general in S0. The related mitochondrial peptide MOTS-c is named on the list as a metabolic modulator. Athletes in the Netherlands can check with the Dopingautoriteit.

What is the difference between humanin and HNG?

HNG (S14G-humanin) is a synthetic variant with glycine instead of serine at position 14. In cell tests it works at concentrations about 1,000 times lower than native humanin, and many animal studies used HNG rather than humanin. They are different substances: amounts, effects and risks of one do not translate to the other, and neither has been tested in people.

Does humanin extend lifespan?

Not in mammals so far. Worms engineered to make extra humanin lived about 7% longer on average (19.0 against 17.7 days), but in 100 old female mice treated with HNG for 14 months lifespan did not change, even though metabolic markers improved. In people, blood levels have been linked to longevity in some studies and to poorer health in others; none of this shows that giving humanin would lengthen life.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.