A 24-amino-acid peptide coded in mitochondrial DNA that protects cells in lab and animal studies. It has never been given to a human in a published study.
Also called HN, Humanin-like peptide, MT-RNR2 peptide, HNG, S14G-humanin, [Gly14]-humanin, Humanin-G
When Humanin's status or evidence changes, it's in the next morning's email.
Humanin is a short peptide, 24 amino acids long, encoded by a small stretch of the mitochondrial genome inside the 16S ribosomal RNA gene. Japanese researchers found it in 2001 while screening for genes that stop nerve cells from dying in models of Alzheimer's disease. It was the first of a group now called mitochondrial-derived peptides, which also includes MOTS-c. Humanin circulates in human blood, and cells release it under stress.
In cell and animal studies it protects many cell types from death. It binds two receptor systems on cell surfaces, FPRL1 and a three-part receptor of CNTFR, WSX-1 and gp130, and it binds IGFBP-3. A lab-made version with one change, HNG (glycine for serine at position 14), is about 1,000 times more potent and is the form used in most animal experiments. In rats, humanin infused into the brain improved whole-body insulin sensitivity. In middle-aged mice, HNG twice a week improved some metabolic health measures, and worms engineered to make more humanin lived longer.
Human data are observational only. Blood levels have been measured in hundreds of people, with conflicting results: some studies found levels fall with age, while a study of 693 Italians aged 21 to 113 found they rise, with the highest levels in centenarians. Children of centenarians had higher levels than matched controls, and levels were lower in Alzheimer's disease. No clinical trial has given humanin or HNG to people, and no regulator has approved it.
What it binds to, and what happens inside the body after that, step by step.
Humanin acts both outside and inside cells. Outside, it binds FPRL1, a G-protein-coupled receptor, and a trimeric receptor made of CNTFR, WSX-1 and gp130 that switches on STAT3, which nerve cell protection depends on. It also binds IGFBP-3 with high affinity and blocks IGFBP-3-induced cell death. Its insulin-sensitizing effect in rats ran through the hypothalamus. How much of any of this happens at the levels found in human blood is unknown.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
No published study has given humanin or any analog to a human. Everything about its effects comes from cells, worms, mice and rats. Human research is limited to measuring natural blood levels, and those studies disagree on whether levels rise or fall with age, so they cannot show that taking humanin would do anything.
693 people aged 21 to 113, including centenarians
Humanin, FGF21 and GDF15 were all higher in old age and highest in centenarians; as a group, these stress molecules went with worse handgrip strength and insulin sensitivity, mainly in 70-year-olds.
Read the studyHealthy adults across ages, people with type 2 diabetes, people with Alzheimer's disease
Humanin rose with age in healthy people and was lower in Alzheimer's disease but not in type 2 diabetes.
Read the study30 adults randomized to endurance exercise, resistance exercise or rest
Blood humanin rose after 45 minutes of cycling but not after leg press; levels did not relate to fitness. No humanin was given.
Read the studyCultured nerve cells with familial Alzheimer's genes or amyloid-beta
The newly identified humanin peptide blocked nerve cell death from several Alzheimer's-related insults but not from other causes such as SOD1 mutations.
Read the studyC. elegans, transgenic mice, middle-aged mice on HNG, naked mole-rats; blood from children of centenarians
Extra humanin extended worm lifespan; HNG twice weekly improved metabolic markers in mice; children of centenarians had higher blood levels than controls.
Read the studyRats under insulin clamp; Zucker diabetic fatty rats
Brain infusion of humanin improved insulin sensitivity via hypothalamic STAT3, and a single dose of a potent analog lowered blood sugar in diabetic rats.
Read the studyCentenarian genetic data; APP/PS1/APOE4 mice
A rare P3S variant was enriched in centenarians carrying APOE4 and cut brain amyloid-beta in mice more than normal humanin.
Read the studyWhen a new Humanin study in people is published, the daily email covers it.
These are questions the published research has not answered.
No product containing Humanin is approved as a medicine by the FDA.
Humanin and HNG are sold only as research chemicals. No interventional human trial is registered on ClinicalTrials.gov; the registered humanin studies measure blood or tissue levels in conditions such as kidney injury, heart surgery and kidney transplant. WADA does not name humanin, but S0 bans any substance with no government approval for human therapeutic use.
When the FDA or WADA changes Humanin's status, it's in the next morning's email.
No human half-life has been published for Humanin, so we do not draw a clearance curve. Half-lives quoted online for it are usually estimates from animal data.
No human study or approved label has published a dose for Humanin, so there is no table to show.
No dose of Humanin has been tested in a published human study or approved on a label. Numbers that circulate online come from animal studies scaled up by guesswork or from sellers. We do not reproduce them.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
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Lifespan gains were seen in worms engineered to make more humanin, and HNG improved metabolic markers in middle-aged mice. No human has been given it in a published study.
Some studies found lower levels in older people, but a 693-person study found levels rise with age and peak in centenarians. In that study, higher levels of humanin and two related stress molecules went with worse grip strength and insulin sensitivity, mainly in 70-year-olds.
It protected nerve cells from Alzheimer's-related damage in cell and mouse studies, and levels are lower in people with Alzheimer's. No trial has tested it in people.
HNG is a synthetic analog with glycine replacing serine at position 14, about 1,000 times more potent in lab tests. It does not occur in the body and has no human safety data.
No published stability data for research-grade humanin or HNG.
No published stability data for any solution intended for injection.
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