Peptide Guide · Longevity
Humanin
HN, MT-RNR2 peptide, mitochondrial-derived peptide
Humanin was found by asking what keeps neurons alive in Alzheimer’s disease. It turned out to be a hormone-like peptide coded in your mitochondrial DNA, one that declines as you age and that growth hormone pushes down.
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- Studied for
- Brain protection, insulin sensitivity and healthy aging
- Evidence
- Early research
- Taken as
- As prescribed by a clinician
Humanin, in short
Humanin is a short peptide coded in mitochondrial DNA, discovered in 2001 in a search for factors that protect neurons from Alzheimer’s-related damage. It blocks a cell-death switch called Bax and improves insulin action through the brain in rodents. It is studied for brain health, insulin sensitivity and healthy aging, with evidence from cells, animals and studies of natural human levels.
Medically reviewed by Robert Lufkin, MD (opens in a new tab)
Chief Medical Officer, Vitals Vault · Updated · 12 sources
Before you consider Humanin
How does Humanin work?
Humanin is a small signal that mitochondria, the cell’s power plants, send to the rest of the body.
Blocks a cell-death trigger
In cells, it grabs a protein that sets off cell death and keeps it away from the cell’s power plants.2
Helps the body use insulin
Given into the brain of rodents, it helped the whole body respond better to insulin.3
Longer healthy life in animals
Extra humanin lengthened life in worms. A stronger version improved metabolic health and lowered inflammation in middle-aged mice.9
Humanin benefits: what it is studied for
The research is early. The strongest signals come from cells and animals, and from human studies of natural humanin levels rather than treatment.
- Animal study01
- Animal study02
Insulin sensitivity
In rodent studies it improved insulin action, and a stronger version lowered blood glucose in diabetic rats.3
- Human study03
Natural levels in long-lived families
Children of centenarians had much higher circulating humanin than age-matched controls. No one was given humanin, so this shows a link, not a benefit.9
What the research shows
Early research- 1 · Cells in a lab Studied
Protected neurons from Alzheimer’s-related damage in cell culture and blocked a cell-death protein.12
Shows a mechanism
- 2 · Animals Studied
Improved insulin action in rodents and cognition in aged mice. Extra humanin lengthened life in worms.389
Shows an effect in a body
- 3 · PeopleNot yet
No trials have given humanin to people. Human studies only measured natural levels, which were higher in children of centenarians.97
Shows it works in people
Humanin has the broadest mechanism data of the mitochondrial peptides, with work from groups in Japan, the United States and Sweden. Some authors on the longevity papers disclose consulting ties to a company, CohBar. The human data describe natural levels and associations. Trials of humanin as a treatment have not been published.1897
The full guide to Humanin
Found by asking what keeps neurons alive
A lot of drug discovery starts with a target and looks for something to hit it. Humanin was found the other way around. In 2001, a team led by Ikuo Nishimoto at Keio University in Tokyo screened a library of gene sequences in neurons, exposed the cells to genes that cause familial Alzheimer’s disease, and watched which sequence kept them alive.
One did, and it worked across a wide range of Alzheimer’s genes and against amyloid beta, the protein that clumps in Alzheimer’s brains. It did not protect against every kind of damage. Neurons dying from an expanded polyglutamine protein, the kind behind Huntington’s disease, or from mutant superoxide dismutase-1, linked to ALS, were not rescued. The protection was specific.
The team called the gene Humanin. Its product was a short polypeptide that cells secreted into the surrounding fluid, and the rescue depended on its exact sequence. In other words, it behaved like a signal, made by one cell and able to protect others.
The researchers framed it as a clue for future Alzheimer’s medicines. Two decades later, humanin is better known as the founding member of a new class of hormones, peptides made by your mitochondria, and its story has wandered far from the brain into metabolism, aging and growth hormone.1
Mitochondrial or nuclear? The odd genetics of humanin
Where humanin comes from turned out to be a puzzle in itself. In 2003, a team in La Jolla, California, found that the mitochondrial genome contains an identical open reading frame, a stretch of DNA that can be read into the same peptide, and that the mitochondrial version also works.
They speculated that humanin arose in mitochondria and was later copied into the nuclear genome, which happens to many mitochondrial genes over evolution. Today it is generally described as a mitochondrial-derived peptide, encoded in the 16S ribosomal RNA region of mitochondrial DNA.
In 2016, a computer search of that same region turned up six more short peptides, named small humanin-like peptides, or SHLP1 to SHLP6. Two of them, SHLP2 and SHLP3, shared humanin’s protective effects on cells, and SHLP2, like humanin, fell in the blood with age.
Mitochondria also read DNA with a slightly different code, treating some three-letter words differently from the nucleus, turning certain stop signals into amino acids and certain amino acids into stops. Exactly which machinery builds each of these small peptides is still being worked out, which adds to the puzzle of where humanin really comes from.2610
How humanin works: blocking a cell’s self-destruct switch
Cells have a built-in self-destruct program called apoptosis, and one of its triggers is a protein called Bax. Bax sits quietly in the cell until a death signal arrives. Then it changes shape, moves to the mitochondria, punches holes in their membranes and releases cytochrome c, which sets the rest of the program in motion.
The 2003 La Jolla study showed that humanin binds Bax and stops it from moving to the mitochondria. Humanin peptides also blocked Bax from attaching to isolated mitochondria and suppressed the release of cytochrome c. When the researchers lowered humanin levels in cells, the cells became more sensitive to Bax.
That gives humanin a clear job inside the cell, guarding the mitochondria against one of the main drivers of cell death. Outside the cell, it acts more like a hormone, traveling in the blood and signaling through the brain, which is where the insulin story begins.
Its protection is not limited to neurons. A 2020 study described humanin as both neuroprotective and cytoprotective, meaning it shields many cell types, and mice engineered to make more of it were better protected against toxic insults. That breadth fits a molecule whose core job is to keep the cell’s death machinery switched off under stress.23
Humanin for brain health and memory
The brain was humanin’s first home. In the 2001 work, it protected neurons in culture against a wide range of Alzheimer’s-related insults. In 2018, a USC-led study showed that humanin protected human cells in culture and was enough to improve cognition in aged mice.
The same study looked at people. Using mitochondrial genetics, the team identified a single-letter variant, rs2854128, in the humanin-coding region that is linked to lower circulating humanin. In a large, nationally representative sample of older adults, carriers of that variant showed accelerated cognitive aging.
A 2020 study added that humanin levels are lower in people with Alzheimer’s disease and in MELAS, a mitochondrial disease that causes stroke-like episodes. None of this shows that giving humanin protects the brain in people. It does show that, in humans, a variant linked to lower humanin in one group tracked with faster cognitive aging in another.
There is also a metabolic bridge. The Einstein team that studied humanin and insulin argued that it links type 2 diabetes and neurodegeneration, two age-related diseases that share insulin resistance. If that view holds, the same falling signal may help explain why the brain and blood sugar so often decline together.189
Humanin and insulin sensitivity
Insulin resistance and Alzheimer’s disease travel together, so in 2009 a team at Albert Einstein College of Medicine asked whether humanin affects insulin. Using clamp studies, the gold-standard method for measuring insulin sensitivity, they infused humanin into the brains of rodents and saw whole-body insulin sensitivity improve.
The effect ran through STAT3 signaling in the hypothalamus, the brain’s metabolic control center, and blocking that signal cancelled it. Even when potent humanin analogs were given intravenously, their effect on the liver depended on the hypothalamus. A single dose of one analog lowered blood glucose in Zucker diabetic fatty rats, a model of type 2 diabetes.
The same paper found that humanin levels in the hypothalamus, skeletal muscle and cortex fell with age in rodents, and that circulating levels fell with age in both mice and people. The authors proposed that this decline could help explain why diabetes and neurodegeneration both become more common with age.
Exercise may push back. In a 2016 Swedish and Finnish study of 55 men with impaired glucose regulation, twelve weeks of resistance training raised humanin protein in thigh muscle by 35%. Blood levels did not change, but blood humanin correlated with improvement in a glucose tolerance test in the training group.37
Growth hormone and humanin pull in opposite directions
The most surprising humanin finding has nothing to do with the brain. In 2014, researchers looked at mice with altered growth hormone signaling. Ames dwarf mice, which lack growth hormone and live unusually long, had elevated humanin. Mice engineered to make extra growth hormone, which live shorter lives, had reduced humanin.
Then they tested it directly. Treating mice with growth hormone or IGF-1, the main hormone growth hormone drives, lowered circulating humanin. The same happened in human subjects given growth hormone or IGF-1. Across the mouse models, humanin levels tracked with lifespan.
This matters for anyone interested in peptides, because many popular ones are designed to raise growth hormone or IGF-1. The hypothesis that follows is straightforward. Pushing the growth hormone axis up may push humanin down, trading one signal linked to longevity for another linked to growth.
None of the studies cited here measured humanin in people taking growth hormone-raising peptides, and the long-term meaning of a lower humanin level is unknown. Treat this as a question worth asking your clinician, and a reminder that hormones in the body rarely move alone.4
Humanin and longevity: worms, mice, mole-rats and centenarians
In 2020, a large collaboration tested humanin across species. In C. elegans worms, overexpressing humanin was enough to extend lifespan, through a longevity gene called daf-16, the worm version of FOXO. Mice engineered to make more humanin were better protected against toxic insults.
Middle-aged mice treated with HNG, a potent humanin analog, showed better metabolic health and lower inflammatory markers. In the species studied, humanin generally falls with age, but in the naked mole-rat, a rodent that barely shows signs of aging, levels stayed surprisingly stable.
The human finding is the one people remember. Children of centenarians, who are more likely to reach 100 themselves, had much higher circulating humanin than age-matched people without that family history. It is an association, and it cannot say whether humanin helps them live longer or simply marks something else that does.
One more detail makes the story more credible. Humanin is described as conserved across animals, and evolution tends to keep sequences that do useful work. A peptide that turns up in long-lived families, in a rodent that barely ages and in lifespan experiments in worms earns serious attention, even before a single human treatment trial.9
Humanin vs MOTS-c
Humanin was the first of the small mitochondrial-derived signaling peptides to be identified, and its discovery prompted the search that turned up MOTS-c in 2015. MOTS-c comes from the neighboring 12S ribosomal RNA gene, while humanin and the six SHLPs come from the 16S gene.
The two are studied for overlapping goals through different routes. MOTS-c acts mainly on skeletal muscle, switching on the energy sensor AMPK and improving how muscle uses glucose. Humanin improves insulin action largely through the brain, via the hypothalamus, and protects cells by blocking the cell-death protein Bax.
Both are studied for healthy aging, both have strong animal data, and neither has published human treatment trials. The practical difference today is regulatory. MOTS-c can be compounded by 503A pharmacies with a prescription under FDA’s October 2026 policy, and humanin cannot.5103212
Humanin side effects, safety and the human evidence
We found no published human trial of humanin as a treatment. The human data described here measure natural humanin, its genetics, and how it responds to exercise or to growth hormone and IGF-1 treatment. None of them gave people humanin. The safety of taking humanin, at any dose and for any length of time, is unknown.
Two theoretical concerns follow from its biology. Humanin blocks cell death, and cancer cells survive by avoiding cell death, so its role in tumors is an open question. It also improves insulin action, so it could add to the effect of diabetes medicines.
It is also fair to know who has done the work. Several authors of the longevity and cognition papers disclose consulting roles and stock in a company, CohBar. The exercise study from Sweden and Finland is one of the independent data points.
People who should talk to a clinician before considering any mitochondrial peptide include anyone with a history of cancer, anyone on diabetes medicine, anyone taking growth hormone or growth hormone-raising peptides, anyone pregnant or breastfeeding, and anyone being treated for a neurological condition.23897
Labs that track the systems humanin is studied in
You cannot order a humanin level as a routine test, but you can measure the systems it is studied in. HbA1c reflects average blood sugar over about three months, and with fasting glucose it is the established test for prediabetes and diabetes. Fasting insulin can rise while glucose still looks normal, though on its own it does not reliably diagnose insulin resistance.
hs-CRP, high-sensitivity C-reactive protein, measures low-grade inflammation. In mice, a humanin analog lowered inflammatory markers, and chronic inflammation is one of the threads connecting metabolic disease and brain aging.
Vitals Vault does not offer humanin. Its panels at Quest Diagnostics measure these markers, and a licensed clinician can help you work on the same systems with training, sleep and nutrition, and with treatments that have stronger evidence.39
Where humanin stands in 2026
Humanin is not an FDA-approved drug. It does not appear on FDA’s April 2026 page of nominated compounding substances with safety concerns, and it is not one of the six peptides FDA’s October 2026 enforcement discretion allows 503A pharmacies to compound.
That leaves no regulated route for humanin as a prescription today. Products sold online as research chemicals are not made for people.1112
What this means for you
Humanin is a peptide your mitochondria make that guards cells against self-destruction, improves insulin action through the brain in rodents and tracks with longer, healthier lives across species. In people, lower levels go with faster cognitive aging, and resistance training raises it in muscle. None of the studies cited here tested it as a treatment in humans.
The useful questions today are about the levers you already control. Are you training for strength? Are your insulin and HbA1c where they should be? And if you take, or are considering, a peptide that raises growth hormone, is it worth asking what that does to the mitochondrial signals your body uses to age well?23974
What to expect with Humanin
Humanin is not available as a prescription, so there is no treatment course to describe. What the research does offer is a time frame for the levers you control. In the exercise study, twelve weeks of progressive resistance training, three sessions a week, raised muscle humanin.
A sensible plan is to measure HbA1c, fasting insulin, glucose and hs-CRP now, train for strength, and retest after about three months to see how the systems humanin is studied in have moved.7
Key Humanin studies
Hashimoto et al., 20011
Functional gene screen in cells · Neuronal cells exposed to Alzheimer’s genes and amyloid beta
Humanin abolished cell death from a wide range of Alzheimer’s insults
Limits: Cell culture only
Guo et al., 20032
Cell and biochemical study · Human cells and isolated mitochondria
Humanin binds Bax and blocks its move to the mitochondria
Limits: Lab work only
Muzumdar et al., 20093
Rodent clamp studies · Rats and mice; human blood levels
Improved insulin sensitivity via the hypothalamus; levels fall with age
Limits: Treatment tested only in rodents
Lee et al., 20144
Mouse models plus human treatment data · Long- and short-lived mice; people given growth hormone or IGF-1
Growth hormone and IGF-1 lowered humanin; humanin tracked with mouse lifespan
Limits: Mostly mouse models
Gidlund et al., 20167
Randomized exercise trial · 55 men with impaired glucose regulation
Resistance training raised muscle humanin by 35%
Limits: No change in blood levels; men only
Yen et al., 20188
Mouse study plus human genetic cohorts · Aged mice; older US adults
Humanin improved cognition in mice; a low-humanin variant tracked with faster cognitive aging
Limits: Human data are associations
Yen et al., 20209
Multi-species study · Worms, mice, naked mole-rats, children of centenarians
Humanin extended worm lifespan and was higher in children of centenarians
Limits: Human data are associations
Humanin myths and evidence
Humanin is a proven anti-aging treatment
No published study we found has tested it as a treatment in people. The evidence comes from cells, animals and observational human studies of natural levels.98
Mitochondria only make energy
Mitochondria also make signaling peptides from their own DNA, including humanin, MOTS-c and six humanin-like peptides. Some, including humanin and SHLP2, have been found circulating in the blood, though how hormone-like each one is varies.65
Raising growth hormone is always good for aging
Growth hormone and IGF-1 lowered humanin in mice and people, and long-lived growth hormone-deficient mice had high humanin. The relationship between the two is more complicated than more is better.4
You cannot change your humanin levels
In men with impaired glucose regulation, twelve weeks of resistance training raised humanin protein in muscle by 35%.7
How is Humanin taken?
Humanin dosage
There is no FDA-approved dose of humanin, and no human dose has been published. The human studies so far measure the humanin the body makes; none gave humanin to people. Animal doses do not translate to people. A prescribing clinician would have to decide any use.
Typical Humanin dosage
No human dose of humanin has been published. We found no trial giving humanin to people in PubMed or on ClinicalTrials.gov; the human studies only measure the humanin the body makes, in blood or muscle. Animal doses do not translate to people. A clinician would have to decide any use and dose.
Already have a prescribed dose? The peptide dosage calculator turns it into the units to draw on an insulin syringe.
No dose has been published from studies in people yet, so there is no typical dose to show. A prescribing clinician decides whether Humanin fits and how it is given.
Is Humanin right for you?
A clinician makes the call. These are the questions they will ask first.
It may suit
- Adults interested in mitochondrial health and healthy aging research
- People who want to track insulin, HbA1c and inflammation over time
Talk to a clinician first if you are
- Pregnant or breastfeeding
- A history of cancer, because humanin protects cells from death and its role in tumors is not settled
- Taking diabetes medicine, because humanin influences insulin action
- Taking growth hormone or growth hormone-raising peptides, which lower humanin levels
- Any neurological condition under treatment
Vitals Vault peptide care starts with a blood panel and a licensed clinician, and ends with a retest.
Get early access to peptide careMitochondria talk to the rest of the body
Mitochondria are not only power plants. They send signals to other organs, and humanin is one of them. Levels fall with age in rodents and in people, and a genetic variant linked to lower humanin went with faster cognitive aging in older adults.
How you live may move this signal. In men with impaired glucose regulation, twelve weeks of resistance training raised humanin protein in muscle.873
What else moves the same system
- 01Lift weightsResistance training raised humanin protein in the muscle of men with impaired glucose regulation.
- 02Keep glucose steadyHumanin is linked to insulin action, so keeping fasting insulin in range supports the same system.
- 03Protect sleepSleep affects insulin sensitivity and inflammation, two systems humanin is studied in.
- 04Track inflammationhs-CRP, fasting insulin and HbA1c show the systems humanin is studied in.
Labs to check with Humanin
A blood test before you start and a retest after shows what actually changed for you. It is how Vitals Vault approaches every treatment.
- TestA baseline panel at Quest Diagnostics.
- DecideA licensed clinician reviews your history and results.
- RetestThe same markers again, side by side.
Is Humanin FDA approved?
No. Humanin is not an FDA-approved drug and does not appear on FDA’s compounding safety page (current as of April 22, 2026). It is not one of the six peptides covered by FDA’s October 2026 enforcement discretion. Research so far is in cells, animals and observational human studies of natural levels.11129
Humanin timeline
2001
Humanin is identified as a secreted factor that protects neurons from Alzheimer’s-related cell death.1
2003
Humanin is shown to bind Bax and block a key step in cell death; an identical sequence is found in mitochondrial DNA.2
2009
Humanin is shown to improve insulin sensitivity in rodents, and circulating levels fall with age in humans and mice.3
2014
Growth hormone and IGF-1 are shown to lower humanin levels in mice and people.4
2016
Resistance training raises humanin protein in the muscle of prediabetic men; a related paper names six other mitochondrial peptides.76
2020
Humanin is linked to lifespan in worms and to metabolic healthspan in mice, and is higher in children of centenarians.9
April 2026
FDA’s compounding safety page is updated; humanin does not appear on it.11
Humanin questions
What is humanin used for?
Humanin is studied for neuroprotection, insulin sensitivity and healthy aging. It is not FDA-approved to treat any condition, and we found no published therapeutic human trials.
What are the benefits of humanin?
It protected neurons against Alzheimer’s-related damage in culture, improved insulin sensitivity in rodents, improved cognition in aged mice and extended lifespan in worms. Human data so far are about natural levels, not treatment.
How does humanin work?
It acts as a signal from mitochondria to other tissues. Inside cells it binds Bax, a protein that triggers cell death, and stops it from damaging mitochondria. In the brain it engages STAT3 signaling in the hypothalamus to improve insulin action.
What are the side effects of humanin?
Human safety data for humanin as a treatment have not been published. Because it influences cell survival and insulin action, people with a cancer history or on diabetes medicine need a clinician’s input.
What is the humanin dosage?
There is no FDA-approved dose, and no human dose has been published: no trial has given humanin to people. Animal doses do not translate to people. A prescribing clinician would have to decide any use.
Humanin vs MOTS-c, what is the difference?
Both are mitochondrial-derived peptides. Humanin comes from the 16S rRNA region and is best studied for neuroprotection and insulin action. MOTS-c comes from the 12S region and is studied for muscle, exercise and glucose use.
Is humanin FDA approved?
No. Humanin is not an FDA-approved drug, does not appear on FDA’s April 2026 compounding safety page, and is not one of the six peptides covered by FDA’s October 2026 compounding policy.
Do humanin levels decline with age?
Yes in rodents and humans. Circulating levels fall with age, and a variant that lowers levels was linked to faster cognitive aging in older adults. Growth hormone and IGF-1 also push levels down.
Can I get humanin through Vitals Vault?
Not at this time. Vitals Vault is opening clinician-led peptide care that starts with a blood test, and humanin is not part of it. Join the peptides waitlist to hear what is offered.
Peptides, prescribed and measured
Vitals Vault is opening peptide care that starts with your blood work, is prescribed by licensed US clinicians and ends with a retest. Join the waitlist to hear first.
- Prescription only
- Licensed US clinicians
- Quest Diagnostics labs
Keep reading
Full Peptide Guide- MOTS-cA peptide coded in your mitochondrial DNA, studied for insulin sensitivity, weight and exercise capacity.
- EpitalonA four-amino-acid pineal peptide studied for telomeres, melatonin and healthy aging.
- GHK-CuA copper-binding tripeptide found in human blood, studied for skin repair, collagen and hair.
- FDA peptide update 2026What FDA’s October 2026 decision on six peptides means for you.
- GlutathioneThe body’s main antioxidant, a three-amino-acid peptide sold as a supplement and given by IV in clinics.
Sources
- 1. Hashimoto Y, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Abeta. Proc Natl Acad Sci U S A. 2001 (opens in a new tab)
- 2. Guo B, et al. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature. 2003 (opens in a new tab)
- 3. Muzumdar RH, et al. Humanin: a novel central regulator of peripheral insulin action. PLoS One. 2009 (opens in a new tab)
- 4. Lee C, et al. IGF-I regulates the age-dependent signaling peptide humanin. Aging Cell. 2014 (opens in a new tab)
- 5. Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 (opens in a new tab)
- 6. Cobb LJ, et al. Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. Aging (Albany NY). 2016 (opens in a new tab)
- 7. Gidlund EK, et al. Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism. Physiol Rep. 2016 (opens in a new tab)
- 8. Yen K, et al. Humanin prevents age-related cognitive decline in mice and is associated with improved cognitive age in humans. Sci Rep. 2018 (opens in a new tab)
- 9. Yen K, et al. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY). 2020 (opens in a new tab)
- 10. Kal S, et al. Mitochondrial-derived peptides: antidiabetic functions and evolutionary perspectives. Peptides. 2024 (opens in a new tab)
- 11. FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (current as of April 22, 2026) (opens in a new tab)
- 12. NCPA. FDA grants enforcement discretion for compounding six peptides. October 29, 2026 (opens in a new tab)