Humanin
Humanin scored 5.4 / 10 (⚖️ Neutral) on the BioHarmony scale as a Substance → Peptide → Other Peptide.
Humanin is a 24-amino-acid mitochondrial-derived peptide that declines with age and runs much higher in children of centenarians, per Yen 2020, but it scores Neutral because zero human interventional trials of injected humanin exist and one 693-person cohort tied high levels to worse outcomes, per Conte 2019.
What is Humanin?
Humanin is a tiny peptide your own mitochondria make, and that is the whole reason it is so interesting. It is a 24-amino-acid mitochondrial-derived peptide encoded inside your mitochondrial DNA, which means it is a native signal your body already produces, not a foreign drug invented in a lab. It scores Neutral at 5.3 because the biology is genuinely compelling while the human proof is missing. Researchers found that children of centenarians, who tend to live unusually long themselves, carry much higher circulating humanin, and that the peptide generally declines as people age, per Yen 2020. That is the kind of longevity-association story that gets attention. The catch, and it is a big one, is that no one has ever run a human trial that injects humanin and measures whether it actually helps.
Humanin was first cloned in a search for what kept a few neurons alive in an Alzheimer's brain, and the gene that turned up encoded a small secreted peptide that stopped neuronal death, per Hashimoto 2001. Since then it has been cast as the cytoprotective, cell-survival half of a two-peptide family, with its sister MOTS-c playing the metabolic, exercise-mimetic role. Humanin works mostly through cell-survival signaling: it engages a receptor called FPRL1, binds a protein called IGFBP-3, and routes through the JAK and STAT3 pathway. The honest summary is a legitimate, conserved, age-declining mitochondrial signal with a clean mechanism and an empty human interventional file. That gap, not the biology, is what holds the score at Neutral.
Terminology
A few terms decide how you read this report, because the distance between an interesting molecule and a proven therapy is exactly where humanin sits. The most important distinction is between observational and interventional evidence, and the second is between native humanin and the much stronger lab analogue most studies actually used. Get those two right and the rest of the report falls into place.
- MDP: Mitochondrial-derived peptide. A small protein encoded inside mitochondrial DNA rather than the cell nucleus. Humanin and MOTS-c are both MDPs.
- HNG: Humanin-G, a synthetic version of humanin with an S14G change that makes it roughly 1000 times more potent. Most headline studies used HNG, not native humanin.
- Interventional trial: A study that gives people the actual substance and measures what happens. Humanin has none of these.
- Observational study: A study that measures a natural marker, such as how much humanin someone already has, against an outcome like age or survival. All the human humanin data is this type.
- Retrograde signaling: Mitochondria talking back to the rest of the cell and body to coordinate stress and survival. Humanin is a classic example.
- FPRL1: A cell-surface receptor humanin uses, the same one amyloid-beta exploits.
- IGFBP-3: Insulin-like growth factor binding protein 3. Humanin binds it, which links the peptide to a cell-survival axis and to a theoretical cancer caution.
- Mitokine: A signal released from mitochondria that travels to other tissues. Humanin is studied as one alongside FGF21 and GDF15.
How do you take Humanin?
Dosing & Protocols
Dosing information is summarized from published research and community reports. This is not a prescribing guide. Consult a healthcare provider before starting any protocol.
View 1 route and 4 protocols
Routes & Forms
| Route | Form | Clinical Range | Community Range |
|---|---|---|---|
| Subcutaneous injection | Lyophilized powder reconstituted with bacteriostatic water; verify identity and purity by certificate of analysis | No approved clinical dose | Native humanin roughly 1 to 3 mg, 2 to 3 times weekly; HNG analogue roughly 100 to 500 mcg, 2 to 3 times weekly |
Protocols
Conservative native humanin (anecdotal) Anecdotal
- Dose
- 1 mg
- Frequency
- 2 times weekly
- Duration
- 8 to 12 weeks, then a 4 to 6 week break
Mirrors the twice-weekly cadence used in the preclinical mouse longevity work, scaled to grey-market human practice. No human dose validation exists.
Standard native humanin (anecdotal) Anecdotal
- Dose
- 1 to 3 mg
- Frequency
- 2 to 3 times weekly
- Duration
- 8 to 12 weeks per cycle
The most commonly cited community range. Subcutaneous is the norm. Doses and cycle lengths are unstandardized across vendors and guides.
HNG analogue (anecdotal, higher potency) Anecdotal
- Dose
- 100 to 500 mcg
- Frequency
- 2 to 3 times weekly
- Duration
- 8 to 12 weeks per cycle
HNG is far more potent than native humanin, so the absolute mass is much lower. Most preclinical longevity and metabolic data leaned on HNG, but it has no human trials either.
Stacked with MOTS-c (anecdotal positioning) Anecdotal
- Dose
- Native humanin 1 to 3 mg plus MOTS-c per its own protocol
- Frequency
- 2 to 3 times weekly
- Duration
- 8 to 12 weeks per cycle
Community framing pairs humanin (the cytoprotective arm) with MOTS-c (the metabolic arm) as two halves of the mitochondrial-derived-peptide stack. The pairing itself is anecdotal, not trial-tested.
How this score is calculated →
What are the benefits of Humanin?
Upside contribution: 1.91
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Efficacy | 25% | 2.8 | 0.700 | |
| Breadth | 15% | 3.2 | 0.480 | |
| Evidence | 25% | 3.0 | 0.750 | |
| Speed | 10% | 2.8 | 0.280 | |
| Durability | 10% | 2.2 | 0.220 | |
| Bioindividuality | 15% | 3.2 | 0.480 | |
| Total | 2.910 |
Upside Rationale
The upside comes almost entirely from mechanism and from one striking human association, not from proven results. Humanin's real assets are a coherent, reproducible cytoprotective and insulin-sensitizing mechanism, plus an eye-catching longevity correlation in the children of centenarians, per Yen 2020. Its hard ceiling is that no human interventional trial of administered humanin exists, so every efficacy claim rests on cells, animals, or correlations. Breadth and bioindividuality score moderately because the biology plausibly touches many systems and the most likely responders are easy to describe. Evidence quality is the dimension that both gives and takes away, since the mechanism is strong but the human interventional column is empty.
Efficacy (2.8/5.0): Efficacy is moderate because humanin's effects are consistent in models yet entirely unproven as a human therapy. In rodents, central humanin improved whole-body insulin sensitivity through hypothalamic STAT3 and potent analogues lowered blood glucose, per Muzumdar 2009, and in cells it abolished neuronal death from Alzheimer's insults, per Hashimoto 2001. Those are real, reproducible signals. What is missing is any human interventional effect size, because no trial has ever given humanin to people and measured a clinical outcome. The marquee metabolic work also leaned on the far more potent HNG analogue, which is a different molecule. A coherent mechanism without a single human outcome trial cannot score as strongly effective, which is why efficacy lands in the middle rather than the top.
Breadth of Benefits (3.2/5.0): Breadth is humanin's quiet strength, because the peptide plausibly touches several systems at once. It is neuroprotective and anti-apoptotic, per Hashimoto 2001, and insulin-sensitizing centrally, per Muzumdar 2009. On top of that, the published preclinical record adds a suppressor role on hepatic triglyceride secretion, activation of chaperone-mediated autophagy as a recognized proteostasis pathway, and, through the more potent HNG analogue, cardioprotection in cardiac cells. The boundary is that breadth of mechanism is not breadth of proof. Each of these systems has a model-level endpoint, not a human one, so humanin scores well on how many doors it touches and modestly on how many it has actually opened in people. The supporting hepatic, autophagy, and cardiac citations appear in the evidence list below.
Evidence Quality (3.0/5.0): Evidence quality is the most double-edged dimension for humanin. On one side, the mechanism is strong and the human observational longevity dataset is genuinely interesting, built on the centenarian-offspring finding and a 693-person mitokine cohort, per Yen 2020. On the other, there is zero human interventional trial of administered humanin, and the largest human cohort muddied the direction by tying high levels to worse outcomes in the oldest old, per Conte 2019. So humanin has more human observational depth than many grey-market peptides but the same empty interventional column. That combination, a rich mechanistic and correlational base with no efficacy trial, is exactly why evidence lands at the midpoint rather than higher.
In a cohort spanning ages 21 to 113, mitokines including humanin rose with age and were highest in centenarians, yet they tracked with worse handgrip, insulin sensitivity, and triglycerides around age 70 and ran inversely to survival in the oldest subjects. That hormetic pattern is the honest counterweight to any simple claim that more humanin means a longer life. Conte 2019, J Gerontol A Biol Sci Med Sci
Speed of Onset (2.8/5.0): Speed is mixed and largely theoretical for humanin. At the cell level, cytoprotective signaling is fast, with survival pathways engaging quickly in vitro. The problem is that the outcomes people actually care about, longevity insurance, neuroprotection, and metabolic resilience, are slow, months-scale processes, and none of them has been measured in a human on humanin. The preclinical longevity work dosed mice twice weekly over time rather than chasing an acute effect, per Yen 2020. Because the felt effects are described as protective rather than noticeable, there is no reliable human onset timeline to point to. The score sits just below the midpoint to reflect fast biochemistry paired with slow, unverified real-world payoff.
Durability (2.2/5.0): Durability is low because humanin is a peptide subject to normal turnover, so any exogenous effect is transient and depends on repeated dosing. Grey-market protocols inject 2 to 3 times weekly precisely because a single dose does not persist, and the preclinical longevity work also treated mice twice weekly rather than once, per Yen 2020. There is no depot effect and no evidence of lasting benefit after stopping. When dosing ends, circulating humanin drifts back toward the person's own baseline, which itself declines with age, per Muzumdar 2009. This is a maintain-to-keep-it signal at best, which puts durability near the bottom of the range alongside most injected peptides.
Bioindividuality Upside (3.2/5.0): Bioindividuality is a relative bright spot because the most plausible responders are easy to name. The biology points toward aging, insulin-resistant, and low-endogenous-humanin individuals as the people most likely to see anything, since humanin declines with age and central infusion helped insulin action in models, per Muzumdar 2009. A specific genetic angle exists too: carriers of a humanin-region mtDNA SNP had lower circulating humanin and faster cognitive aging, per Yen 2018, which hints at a measurable responder profile. The centenarian-offspring biology adds a heritable longevity dimension on top of that genetic signal. These predictable modifiers lift the score, even though they remain hypotheses until a human trial tests them.
What are the risks & downsides of Humanin?
Downside contribution: 1.57 (safety risks weighted extra)
| Dimension | Weight | Score | Visual | Weighted |
|---|---|---|---|---|
| Safety | 30% | 2.4 | 0.720 | |
| Side effects | 15% | 2.0 | 0.300 | |
| Cost | 5% | 2.8 | 0.140 | |
| Effort | 5% | 3.0 | 0.150 | |
| Opportunity | 5% | 2.8 | 0.140 | |
| Dependency | 15% | 2.0 | 0.300 | |
| Reversibility | 25% | 1.8 | 0.450 | |
| Total | 2.200 | |||
| Harm subtotal × 1.4 | 2.478 | |||
| Opportunity subtotal × 1.0 | 0.430 | |||
| Combined downside | 2.908 | |||
| Baseline offset (constant) | −1.340 | |||
| Effective downside penalty | 1.568 |
Downside Rationale
The downside is dominated by uncertainty and sourcing risk rather than acute danger from the molecule itself. As an endogenous peptide present across the human lifespan, humanin carries no documented intrinsic catastrophic signal in the published literature, per Conte 2019, and it clears on stopping. The heavier weights come from a real but theoretical oncologic caution tied to chronic pro-survival signaling, the recurring injection burden, and the opportunity cost of spending effort on an unproven peptide when better-evidenced longevity levers exist. Dependency is essentially nil and reversibility is excellent. The dominant practical hazard is extrinsic: grey-market product with genuine sterility and purity risk.
Children of centenarians carry much greater circulating humanin than age-matched controls, and humanin overexpression extends lifespan in worms, which is the single most cited reason people find this peptide interesting. Yen 2020, Aging (Albany NY)
Safety Risk (2.4/5.0): Safety risk is moderate and driven by unknowns rather than a confirmed hazard. Humanin is an endogenous peptide present in human circulation throughout life, per Conte 2019, and the published preclinical literature shows no organ failure, no carcinogenicity signal, and no death-causing mechanism attributable to the peptide, so nothing in the evidence reaches a worst-case safety floor. The real caution is theoretical: because humanin is pro-survival and engages the IGFBP-3 axis, per Ikonen 2003, chronically raising a survival signal could be unwise in the setting of existing cancer. No human data confirm harm, but the absence of any long-term human safety study, combined with that mechanistic flag, keeps safety below the midpoint rather than fully reassuring.
Side Effect Profile (2.0/5.0): The side-effect profile is one of humanin's cleaner dimensions on current evidence. Reported issues in grey-market practice are limited to minor injection-site reactions such as redness and mild swelling, with no consistently reported systemic adverse effects at the doses people use. The important qualifier is that this is anecdotal and off-label, not trial-derived, so the apparent cleanliness partly reflects how little has been measured. There is no human safety trial to confirm a side-effect rate, and an endogenous peptide given by injection still carries the ordinary risks of any subcutaneous shot. The low score reflects a genuinely mild reported profile tempered by the thinness of the data behind it.
Financial Cost (2.8/5.0): Cost is moderate and recurring. Native humanin and the HNG analogue are sold as grey-market research chemicals, and while HNG's high potency keeps the absolute mass per dose low, the 2 to 3 times weekly injection cadence means the spend adds up across a multi-week cycle. Add in bacteriostatic water, syringes, and optional IGF-1 testing, and a real cycle runs into the low hundreds of dollars per month. It is not expensive per dose; the relevant framing is ongoing spend on a peptide with no proven human payoff.
Time/Effort Burden (3.0/5.0): Effort is meaningful and easy to underestimate. Humanin requires reconstituting a lyophilized powder with bacteriostatic water, subcutaneous injection 2 to 3 times weekly, cold-chain storage after reconstitution, and rotating injection sites. That is a real daily and weekly logistics load compared with an oral capsule, and the need to verify you actually received what you paid for adds a sourcing chore on top. None of this is extreme, but it is enough friction that it earns a score right at the midpoint.
Opportunity Cost (2.8/5.0): Opportunity cost is real because humanin competes for attention and budget with better-evidenced longevity levers. Money and effort spent on an unproven injectable could go toward interventions that at least have some human interventional data, such as the NMN NAD precursor or epitalon, or toward the training, sleep, and nutrition basics that move healthspan with far more certainty. The score stays just below the midpoint rather than higher because humanin is low-suppression and does not interfere with other tools, so running it does not actively sabotage a stack the way some interventions can.
Dependency/Withdrawal (2.0/5.0): Dependency risk is low. Humanin has no addictive mechanism and no rebound or withdrawal syndrome, so its effects simply fade toward your own baseline when dosing stops. There is no hormonal axis it shuts down and no documented tolerance pattern beyond the general expectation that a transient peptide needs repeat dosing to keep any effect going. The score sits low to reflect functional reliance, where benefits depend on continued use, rather than any true dependency.
Reversibility (1.8/5.0): Reversibility is excellent and one of humanin's genuine strengths. As a peptide subject to normal turnover, exogenous humanin clears after you stop, and circulating levels return toward your endogenous baseline, per Muzumdar 2009. There is no taper requirement, no lasting structural change, and no documented persistent effect once a cycle ends. A low reversibility score here means a clean stop, which is exactly what you want from an experimental compound: if it does not suit you, walking away leaves no lingering footprint beyond your own natural levels.
Is Humanin worth it?
Humanin is one of the more biologically interesting longevity peptides on the board, and it lands at Neutral because fascinating biology cannot outrun an empty human file. It is a real, conserved, endogenous mitochondrial signal that declines with age, runs high in the children of centenarians, and carries a clean cytoprotective and insulin-sensitizing mechanism, per Yen 2020. For someone chasing neuroprotection or longevity insurance, the safety posture is reassuring and the mechanism is legitimate. The honest ceiling is hard: no human interventional trial of administered humanin exists, the largest human cohort tied high levels to worse outcomes in the oldest old, per Conte 2019, the marquee work leaned on the unapproved HNG analogue, and the only product available is grey-market research chemical. This is an experiment-if-you-must intervention, not a recommendation.
✅ Best for: Aging adults who find the mitochondrial-derived-peptide biology genuinely compelling and want to run a careful self-experiment with eyes open. Insulin-resistant individuals drawn to the central insulin-sensitizing mechanism shown in rodents, who will track fasting glucose and HbA1c rather than assume benefit. People with a low-endogenous-humanin profile, such as carriers of the humanin-region mtDNA SNP, who fit the most plausible responder description. Citizen-science-minded users who accept research-peptide risk, will log objective biomarkers, and treat humanin as a contribution to their own data rather than a proven therapy. Anyone who can independently verify source sterility, identity, and purity by certificate of analysis.
❌ Avoid if: You have active, recent, or suspected cancer, because chronically raising a pro-survival signal that engages the IGFBP-3 axis is a real theoretical concern even without confirming human data. You are pregnant or breastfeeding, since there is no safety data in those states. You want proven results, because no human interventional trial supports any humanin claim and the largest human cohort points in a conflicting direction. You cannot vet your source, since grey-market peptides carry genuine sterility, identity, and endotoxin risk that can exceed the molecule's own modest hazard. You would rather put limited budget toward a longevity lever with at least some human interventional evidence behind it.
What is Humanin best for?
The overall BioHarmony score reflects the intervention's primary evidence profile. These subratings are independent assessments per use case.
| Use Case | Score | Summary |
|---|---|---|
| ○ Longevity / Lifespan Primary | 3.0 | Longevity is humanin's most interesting and most cited use case, yet it stays modest because the human evidence is correlational, not interventional. Children of centenarians carry much higher circulating humanin, the peptide extends lifespan in worms in a daf-16 and FoxO dependent way, and it generally declines with age across species, per Yen 2020. The honest counterweight is that a 693-person cohort tied high mitokine and humanin levels to lower survival in the oldest old, per Conte 2019. No trial has administered humanin to humans and measured a survival or aging endpoint, so the score reflects a strong association story with an empty interventional column. |
| ○ Neuroprotection Primary | 3.0 | Neuroprotection is where humanin was born and where the preclinical case is strongest, but it lands at a moderate score because it has never been tested as a neuroprotective therapy in people. Humanin was discovered as a factor that abolished neuronal death caused by familial Alzheimer's genes and amyloid-beta, per Hashimoto 2001, and it competitively blocks amyloid-beta at the FPRL1 receptor, per Ying 2004. The mechanism is coherent and reproducible in cells and animals, yet there is no human interventional neuroprotection trial, so the rating credits mechanism without claiming proven human benefit. |
| ○ Metabolic Health Primary | 3.0 | Metabolic health is humanin's second-strongest mechanistic story, but it sits at a moderate score because the cleanest data came from rodents and a more potent analogue. Continuous central humanin infusion improved whole-body insulin sensitivity through hypothalamic STAT3, and potent analogues lowered glucose in diabetic rats, per Muzumdar 2009. Central humanin also suppressed hepatic triglyceride secretion, per Gong 2015. No human trial has measured a metabolic endpoint after administered humanin, and the Conte cohort even tied high levels to worse insulin sensitivity at around 70, so the score credits mechanism while flagging the human ambiguity. |
| ○ Mitochondrial Primary | 3.2 | Mitochondrial signaling is the one area where humanin scores slightly higher, because the molecule is itself a mitochondrial product and a textbook example of the retrograde-signaling concept. Humanin is encoded inside mitochondrial DNA and acts as a mitokine that lets mitochondria talk back to the nucleus and distant tissues, per Kim 2017 and Miller 2022. The biology here is well-established rather than speculative. The score still stays modest because being a genuine mitochondrial signal is not the same as proving that injecting more of it helps a person. |
Frequently Asked Questions
What is humanin and how does it work?
Humanin is a 24-amino-acid peptide encoded inside your mitochondrial DNA, which makes it a mitochondrial-derived peptide and a native cytoprotective signal, per Yen 2020. It was discovered as a factor that stopped neuronal death from Alzheimer's genes, per Hashimoto 2001. It signals through the FPRL1 receptor, binds IGFBP-3, and acts through JAK and STAT3 to keep cells alive and to nudge insulin sensitivity centrally.
What does the longevity evidence for humanin actually show?
The longevity case is an association, not proof. Children of centenarians carry much higher circulating humanin, humanin extends lifespan in worms, and it generally declines with age, per Yen 2020. The honest caveat is that a 693-person cohort found high humanin and related mitokines tracking with worse function and lower survival in the oldest old, per Conte 2019. So the human data is correlational and even points in conflicting directions, and no trial has given humanin to people to test it.
Has humanin been tested in human clinical trials?
No. There is no human interventional trial of administered humanin measuring a longevity, cognitive, cardiovascular, or metabolic outcome. The human data is purely observational, meaning researchers measured natural humanin levels against age, longevity, and disease, as in Yen 2020 and the mixed-direction cohort in Conte 2019. Everything about giving humanin as a therapy rests on cells, animals, and the more potent HNG analogue, so no validated human efficacy number exists because no efficacy trial exists.
How is humanin different from MOTS-c?
Humanin and MOTS-c are sister mitochondrial-derived peptides that play different roles. Humanin is the cytoprotective and anti-apoptotic arm, while MOTS-c is the AMPK-driven metabolic and exercise-mimetic arm, per Kim 2017. Both decline with age and both lack human interventional trials. Communities often stack them as two halves of one signaling system, but that pairing is anecdotal. You can compare the metabolic sibling in our MOTS-c report.
What is HNG and why does it matter for humanin?
HNG, also called humanin-G, is a synthetic analogue with an S14G substitution that makes it roughly 1000 times more potent than native humanin, per Yen 2020. Much of the headline metabolic and cardioprotective work used HNG, including the cardiac cell study in Klein 2013. This matters because any claim that humanin works often leans on a different, more potent molecule. HNG is also entirely non-clinical, with no human trials of its own.
Is humanin safe to use?
Humanin has no documented intrinsic catastrophic signal in the published literature, and as an endogenous peptide already present across the lifespan, per Conte 2019, its risk posture differs from a foreign drug. The honest gaps are real: there is no long-term human safety data, and because humanin is pro-survival and engages the IGFBP-3 axis, per Ikonen 2003, there is a theoretical caution against chronic use with existing cancer. Grey-market sterility risk is a separate, practical hazard.
How do people dose humanin, and is there an approved dose?
There is no approved or validated human dose for humanin. Anecdotal grey-market protocols cite roughly 1 to 3 mg of native humanin subcutaneously, 2 to 3 times weekly, or 100 to 500 mcg of the far more potent HNG analogue at a similar cadence, often in 8 to 12 week cycles. These figures are reconstructions of off-label community practice with no FDA label, no validated therapeutic window, and no published human dose-response data, so treat every number as unverified.
Who is humanin for, and who should avoid it?
Humanin suits aging or insulin-resistant adults who find the biology compelling, accept research-peptide risk, will track objective markers, and treat it as an experiment rather than a therapy. It is not a recommendation, because no human interventional trial supports it. Avoid it with active or recent cancer, given the theoretical pro-survival concern, during pregnancy or breastfeeding with no safety data, or if you cannot vet a sterile, verified source. For better-evidenced longevity levers, see our NMN report and epitalon report.
What could change Humanin's score?
BioHarmony scores are living assessments. New research, regulatory changes, or personal context can shift the score up or down. These are the most likely scenarios that would change this intervention's rating.
The fastest way humanin moves up is a genuine human interventional trial, and the fastest way it drops is a credible human harm signal. Because the current score rests on a strong mechanism with an empty human efficacy column, even modest real human data would shift it more than usual. The dimensions most likely to move first are Evidence and Efficacy on the upside, and Safety on the downside, since a confirmed oncologic or hormetic harm signal would force a worst-case reassessment.
| Scenario | Dimension shifts | New Score |
|---|---|---|
| A human trial of humanin or HNG shows a meaningful neuroprotective, cognitive, or metabolic benefit | Evidence 3.0 to 3.8, Efficacy 2.8 to 3.6 | 5.9 / 10 👍 Worth trying |
| The centenarian-offspring association replicates with a prospective survival outcome, resolving the cohort ambiguity | Evidence 3.0 to 3.4, Bioindividuality 3.2 to 3.6 | 5.6 / 10 ⚖️ Neutral |
| Dedicated human pharmacokinetic data validates dosing without an outcome | Evidence 3.0 to 3.2 | 5.5 / 10 ⚖️ Neutral |
| A human signal suggests chronic humanin or HNG promotes tumor growth | Safety 2.4 to 4.0, Evidence 3.0 to 2.6 | 4.6 / 10 ⚖️ Neutral |
| A documented contamination or adverse-event cluster emerges from grey-market product | Safety 2.4 to 3.2, Side Effects 2.0 to 2.8 | 4.8 / 10 ⚖️ Neutral |
| A human trial of administered humanin fails to beat placebo for a marketed use | Efficacy 2.8 to 2.0, Evidence 3.0 to 2.4 | 5.0 / 10 ⚖️ Neutral |
Key Evidence Sources
- Hashimoto 2001, PNAS: a rescue factor (Humanin) abolished neuronal death caused by familial Alzheimer's genes and amyloid-beta.. 2001 discovery paper establishing humanin's neuroprotection in a cell model
- Ikonen 2003, PNAS: humanin binds IGFBP-3 and modulates IGFBP-3-driven apoptosis, linking it to the IGF survival axis.. 2003 mechanistic study identifying the humanin and IGFBP-3 interaction
- Ying 2004, J Immunol: humanin uses the formylpeptide receptor FPRL1 and competitively blocks amyloid-beta at that receptor.. 2004 receptor study defining the FPRL1 mechanism
- Hashimoto 2005, Life Sci: tyrosine-kinase-dependent STAT3 activation mediates humanin neuroprotection.. 2005 signaling study placing STAT3 downstream of humanin
- Muzumdar 2009, PLoS One: central humanin infusion improved whole-body insulin sensitivity via hypothalamic STAT3; circulating humanin fell with age.. 2009 rodent study on central insulin action and the age-related decline
- Klein 2013, Biochem Biophys Res Commun: the humanin analogue HNG reduced oxidative stress and preserved mitochondrial integrity in cardiac myoblasts.. 2013 cardioprotection study using the more potent HNG analogue
- Gong 2015, Am J Physiol Endocrinol Metab: central humanin suppressed hepatic triglyceride secretion in a rodent model.. 2015 metabolic study on hepatic lipid handling
- Kim 2017, J Physiol: review of mitochondrially derived peptides as regulators of metabolism and retrograde signaling.. 2017 review framing humanin and MOTS-c as complementary mitokines
- Gong 2018, J Cell Biol: humanin is an endogenous activator of chaperone-mediated autophagy.. 2018 proteostasis study tying humanin to chaperone-mediated autophagy
- Yen 2018, Sci Rep: humanin improved cognition in aged mice and a humanin-region mtDNA SNP tracked with accelerated cognitive aging in people.. 2018 cognitive-aging study with a human genetic-epidemiology arm
- Conte 2019, J Gerontol A Biol Sci Med Sci: in a 693-person cohort high mitokines including humanin rose with age but tracked with worse function and lower survival in the oldest old.. 2019 human observational cohort, the key counter-signal to the longevity story
- Yen 2020, Aging (Albany NY): the MDP humanin is a regulator of lifespan and healthspan, with much higher levels in children of centenarians.. 2020 landmark longevity-association paper and centenarian-offspring finding
- Miller 2022, J Clin Invest: review of mitochondria-derived peptides in aging and healthspan and their retrograde-signaling role.. 2022 review on MDPs as aging-relevant retrograde signals
What does the evidence say about Humanin?
Evidence on this intervention is summarized across three complementary streams: contemporary clinical research, pre-RCT-era pharmacology and observational use, and the traditional medical systems that documented it first. Convergence across streams signals higher confidence; divergence is surfaced honestly.
Modern Clinical Research
Confidence: Low
Citations: Yen 2020, Conte 2019, Muzumdar 2009, Hashimoto 2001
What to Track If You Try This
These are the data points that matter most while running a 30-day Experiment with this intervention.
How to read this section
- Pre
- Test or score before starting the protocol. Anchors a baseline.
- During
- Track while running the protocol so you can see if anything is changing.
- Post
- Re-test after a full cycle to confirm the change held.
- Up
- The marker should rise. For most positive outcomes, that is a good sign.
- Down
- The marker should fall. For most positive outcomes, that is a good sign.
- Stable
- The marker should hold steady. Big swings in either direction are a yellow flag.
- Watch
- Direction depends on dose, timing, and your baseline. Pay close attention to the trend.
- N/A
- No expected direction. The entry is there to anchor a baseline reading.
- Primary
- The Pulse dimension most likely to shift. Track this first.
- Secondary
- Also relevant, but a smaller or less consistent shift. Track if Primary is unclear.
Bloodwork to Order
Open These Markers In Your Dashboard
- Fasting Glucose Pre | Expected Watch During | Expected Watch
- HbA1c During | Expected Watch
- IGF 1 During | Expected Watch
Pulse Dimensions to Watch
- Energy During | Expected Watch | Primary
- Body During | Expected Watch | Secondary
- Calm During | Expected Watch | Tertiary
Subjective Signals (Daily Voice Card)
- Injection-site redness, swelling, or soreness Scale 1-5 | During | Expected Watch
- Subjective cognitive resilience or clarity over weeks Scale 1-5 | During | Expected Watch
Red Flags: Stop and Consult
- Any active, recent, or suspected cancer: do not use, given the theoretical pro-survival and IGFBP-3 signaling concern.
- Worsening or progressive injection-site reaction with each dose: stop and reassess source quality.
- Any systemic reaction such as fever or spreading redness, which can signal a contaminated grey-market product: stop immediately.
- Pregnancy or breastfeeding: do not use, since there is no safety data.
Other interventions for Longevity
See all ratings →📊 How BioHarmony scoring works
BioHarmony translates a weighted expected-value calculation into a reader-facing 0–10 score. Tier bands: Skip 0–3.6, Caution 3.7–4.7, Neutral 4.8–5.7, Worth Trying 5.8–6.9, Strong Recommend 7.0–7.9, Top-tier 8.0+.
Harm-type downsides (safety risk, side effects, reversibility, dependency) carry a 1.4× precautionary multiplier. Harm weighs more than benefit. Opportunity-type downsides (financial cost, time/effort, opportunity cost) are subtracted at face value.
Use case subratings are independent assessments of how well the intervention addresses specific health goals. They are not components of the overall score. Each subrating reflects the scorer's judgment based on use-case-specific evidence, safety, and effect sizes.
Every dimension is evaluated on a 1–5 scale, and the baseline (1) is subtracted before weighting. A perfect intervention with zero downsides contributes zero penalty rather than a residual floor, so top-tier scores are actually reachable.
EV = Upside − Downside
EV = 1.910 − 1.568 = 0.342
Formula v0.5 maps EV = 0 to score 5.0. Above neutral, 1 EV point equals 1 score point. Below neutral, 1 EV point equals about 0.71 score points, so EV = −7 reaches 0.0 while EV = +5 reaches 10.0. Both sides use the full 5-point half-scale.
Score = 5 + (0.342 / 5) × 5 = 5.3 / 10
