LongevityHNHNG (S14G-humanin, synthetic analog)

Humanin

Endogenous mitochondrial-derived peptide · real biology, no human trials

Humanin is unusual in this library because it is a molecule your own body already makes. It was the first 'mitochondrial-derived peptide' (MDP) ever identified — a 24-amino-acid peptide encoded inside the mitochondrial MT-RNR2 gene — and it carries a large, legitimate basic-science literature on protecting neurons, blocking programmed cell death (apoptosis), and tuning metabolism. The honest issue is the gap between that biology and any actual use. The evidence is almost entirely from cell-culture dishes, rodents, and human observational data: circulating humanin levels fall as people age, and are higher in the long-lived children of centenarians. Those are associations — they do not show that injecting humanin helps anyone. There are essentially zero human interventional trials testing administered humanin for efficacy or safety. A further catch: most of the striking animal results come not from native humanin but from a lab-made super-analog called HNG (S14G-humanin), reported to be roughly 1,000 times more potent — so even the mouse data don't cleanly transfer to the native peptide a vendor would actually sell. There is no approved therapeutic use anywhere, no established human dose, and no human safety dataset. The defensible framing is 'real endogenous biology and a promising aging biomarker'; the unproven leap is 'inject it for longevity.'

The short version

Humanin is a small peptide — 24 amino acids — that your mitochondria, the energy factories inside your cells, actually produce on their own. It was discovered in 2001 as a 'rescue factor' that kept neurons alive in the face of Alzheimer's-related toxicity, and it became the founding member of a class called mitochondrial-derived peptides. So unlike most research peptides, this one is a genuine part of human biology, not a purely synthetic invention.

The science on what it does inside cells is solid in its own lane: humanin blocks apoptosis (the cell's self-destruct program), interacts with specific receptors, and influences insulin and metabolic signaling. But here is the honest core. Almost all of that evidence comes from cells in dishes and from rodents — and in people, what we have is observational: humanin levels in the blood drop with age, and tend to run higher in people who inherit exceptional longevity. Those are correlations. They are interesting clues about aging biology, but they do not prove that giving someone extra humanin does anything good.

Two more cautions a careful reader should hold. First, the most impressive animal results usually used not native humanin but a redesigned, far more potent lab version called HNG — so even the mouse data overstate what the natural peptide does. Second, there are essentially no human trials of injected humanin: no established dose, no efficacy data, and no human safety record at all. The fair summary is that humanin is real, fascinating endogenous biology and a promising marker of healthy aging — but the popular pitch to inject it for longevity rests on extrapolation, not human evidence.

Molecular identity

Specs

Molecular formula: C₁₁₉H₂₀₄N₃₄O₃₂S₂
Molecular weight: 2687.2 g/mol (average)
Monoisotopic mass: 2685.4822 Da
PubChem CID: 16131438

Sequence: MAPRGFSCLLLLTSEIDLPVKRRA (24 AA)PubChem CID 16131438
Type: Mitochondrial-derived peptide (MDP) — first MDP identified; endogenousReviews, J Clin Invest 2022 (PMID 35499074)
Gene / origin: MT-RNR2 open reading frame (within mitochondrial 16S rRNA)Hashimoto et al., PNAS 2001 (PMID 11371646)
Molecular target: Pro-apoptotic Bax antagonism + IGFBP-3 binding; signals via CNTFRα/WSX-1/gp130 receptor complex (cytoprotective)PMID 14561895; PMID 19386761
Synthetic analog: HNG = S14G-humanin (Ser→Gly at position 14); ~1,000× more potent, used in most in-vivo workAnalog literature, Exp Ther Med 2017 (PMID 29043002)
Plasma half-life: Not established for native humanin (no human PK); the only PK study measured the HNG analog in rodents (~30 min mice / >4 h rats, IP) — does not transfer to native peptidePMID 23836030Half-life curve →
Regulatory status: Not approved as a drug anywhere; sold only as a research chemicalRegulatory record (no approval exists)

Plain English

Mechanism

Humanin's best-established biology is cytoprotective — it helps keep stressed cells alive. It antagonizes pro-death signaling from the Bcl-2 family of proteins, notably interfering with the protein Bax, and it binds a circulating protein called IGFBP-3; that humanin–IGFBP-3 interaction regulating cell survival is one of the foundational primary findings. In plain terms, humanin acts as a 'survival signal' that pushes back against programmed cell death.

It also works through specific cell-surface receptors. The best-characterized is a three-part cytokine receptor complex (CNTF-receptor-alpha together with WSX-1 and gp130); humanin was shown to block neuronal death by engaging this complex. A second candidate receptor (a formyl-peptide-receptor-like protein, FPRL1/FPR2) has been implicated but is less firmly pinned down. On the metabolic side, work in rats found humanin acting centrally, in the hypothalamus, to improve the body's insulin sensitivity — a 'central regulator of peripheral insulin action.'

Where to draw the honesty line: the cytoprotective, receptor, and insulin-signaling biology is real and reproduced, but it is cell and rodent work — and the metabolic effects in particular come largely from the more-potent HNG analog. The broader claims of 'longevity,' 'anti-aging,' or 'systemic healthspan' benefits in humans are mechanistic hypotheses and associations, not demonstrated outcomes of administering humanin to people. The reviews treat humanin as a candidate in aging biology, not a proven intervention.

Sources:PMID 14561895 PMID 19386761 PMID 19623253

Why people reach for it

Potential benefits

Humanin is unusual — a peptide your own mitochondria make, with real basic-science behind it. Here's what draws people to it, with the honest core that the human evidence is observational, not interventional.

A molecule your own body makes — Humanin is endogenous — the first mitochondrial-derived peptide ever identified, encoded in the MT-RNR2 gene — so unlike most research peptides it's a genuine part of human biology rather than a purely synthetic compound.
A cell-survival, anti-apoptosis signal — Its best-established biology is cytoprotective: it pushes back against programmed cell death (interfering with the pro-death protein Bax and binding IGFBP-3), which is why it's framed as a 'survival signal' in the research.
A promising marker of healthy aging — Circulating humanin falls with age and runs higher in the long-lived children of centenarians — striking associations that make it an interesting biomarker in aging biology (associations, not proof that injecting it helps).
Studied for metabolic and insulin signaling — In rodent work humanin acted centrally to improve insulin sensitivity — a 'central regulator of peripheral insulin action' — which is why it shows up in metabolic-health discussions.
A natural fit for mitochondrial-support stacks — As a mitochondrial-derived peptide it slots logically alongside other mito-focused agents (NAD+ precursors, MOTS-c, SS-31) that come at mitochondrial biology from a different angle.

Sources:PMID 14561895 PMID 19623253 PMID 25040290 PMID 35499074

What people reach for Humanin for, drawn from what the research reports and how it's used — not proven outcomes or medical claims. Honest limits: the human evidence is observational, there are essentially zero human interventional trials, and most striking animal results used the ~1,000× more potent HNG analog, not native humanin.

Implied timing

Best time to dose

Implied best time

Anytime (consistent)

Most people take Humanin at a consistent daily time — it's a mitochondrial-derived cytoprotective/metabolic peptide with no time-locked action, so regularity matters more than the exact hour.

Humanin's biology — anti-apoptotic survival signaling, receptor-complex activation, metabolic tuning — isn't a process that peaks at one time of day, so there's no mechanistic reason to favor morning over evening.
There's no human pharmacokinetic data for native humanin (its half-life isn't established in people), so there's nothing to time a dose around; a steady daily slot is simply the practical default for once-daily use.
Because it's run as a daily longevity/mitochondrial-support compound, a repeatable time builds the habit and keeps spacing even — which matters more here than any specific hour.

No study establishes an ideal time of day for Humanin — this is reasoned from its mechanism and how it's used. As a rule of thumb most peptide dosing lands in the midday-to-evening window; for Humanin any consistent daily time is fine.

How to run it

Dosing & protocol

Humanin is dosed here as a subcutaneous injection — the form sold as a research peptide and the route the on-page calculator is built for. There is no established human dose: all dosing in the literature comes from rodent studies, mostly using the ~1,000× more potent HNG analog. What follows is community convention assembled from that limited starting point — not a validated protocol. Read it as a map of how people run injectable humanin, with that caveat foregrounded.

No human interventional trials of administered humanin exist anywhere in the literature. Every number here is community convention extrapolated from rodent data (mostly HNG analog) and shared mechanism — doubly unproven. Humanin is not an FDA-approved drug and has no established human safety record.

Tiered dose ranges

Community convention for subcutaneous native humanin; no human trial exists to anchor these numbers.

Low / first run:: 500 mcg (0.5 mg) subcutaneously once daily — the conservative starting point most used to test individual response before escalating.
Standard convention:: 1,000 mcg (1 mg) once daily — the most commonly reported community dose for ongoing longevity and mitochondrial-support goals.
Higher range:: Up to 2,000 mcg (2 mg) once daily — occasionally reported; no additional human rationale over the 1 mg level exists; approach cautiously.
HNG analog note:: HNG (S14G-humanin) is reported ~1,000× more potent than native humanin. If the compound is HNG, doses would be dramatically lower — typically in the nanogram range in animal studies. Vendor products labeled 'humanin' are generally the native peptide.

Subcutaneous administration

Humanin is injected into subcutaneous fat; site selection and rotation are the actionable choices.

Injection site:: The abdomen (staying a couple of inches clear of the navel), the love-handle area, or the outer thigh. Rotate sites between doses to prevent local irritation and lipohypertrophy (fatty lumps from repeated injection at one spot).
Measuring the dose:: Drawn on a U-100 insulin syringe from the reconstituted vial. At the standard mix (10 mg vial + 2 mL BAC water = 5,000 mcg per mL): 500 mcg = 10 IU · 1,000 mcg = 20 IU · 2,000 mcg = 40 IU. The on-page calculator handles any vial size.
Time of day:: No peptide-specific timing data exists for humanin, and it isn't time-locked — a consistent daily time matters more than the exact hour, following general daily-peptide practice. See Best time to dose above.
Food window:: Subcutaneous administration bypasses the gut, so humanin can be injected independently of meals.

Cycle & washout

No human cycle data exist; the conventions below mirror how the community runs other longevity peptides in this class.

Standard cycle:: 4–8 weeks of daily use, then assess. The absence of human safety data argues for shorter initial runs with careful monitoring.
Washout:: A 2–4-week break between cycles is the common convention, both for reassessment and out of general caution about unknown long-term effects on apoptosis and IGF signaling — powerful pathways humanin touches.
Pulsed alternative:: Some community protocols use 5-days-on / 2-days-off rather than continuous daily dosing; no human data supports one pattern over the other for humanin.

Reconstitution at a glance

The on-page calculator does this live; the quick math for the standard 10 mg vial:

Mixing:: 10 mg vial + 2 mL bacteriostatic water = 5,000 mcg per mL. On a 100-unit (1 mL) insulin syringe: 500 mcg = 10 IU · 1,000 mcg = 20 IU · 1,500 mcg = 30 IU · 2,000 mcg = 40 IU.
Why these numbers:: Matching the calculator's default bacWaterMl = 2 mL keeps the on-page numbers consistent. If you prefer a different dilution, use the calculator to recompute syringe units.

Sources:PMID 29043002 PMID 19623253 PMID 35499074

Substrate the signal needs

Nutritional cofactor precision

Humanin is a mitochondrial-derived peptide whose biology centers on cytoprotection, anti-apoptosis, and metabolic / insulin signaling — all processes that run on the same mitochondrial energy machinery. The cofactors below supply and support that machinery. This is mechanistic reasoning mapped onto humanin's known mechanism, not a humanin nutrition study — humanin's own human cofactor data is essentially nil.

Reasoned from humanin's mitochondrial-derived cytoprotective / metabolic mechanism — not a cofactor study of humanin. All supplement doses are general community convention, not humanin-specific findings. Human evidence behind humanin itself is observational and preclinical.

Supply the substrate — NAD+ precursors (NR / NMN) + CoQ10

The mitochondrial energy chain humanin operates within runs on NAD+ and coenzyme Q10; both decline with age on a trajectory that mirrors humanin's own decline.

NAD+ precursors (NR or NMN):: Nicotinamide riboside (NR) 300–500 mg/day or nicotinamide mononucleotide (NMN) 250–500 mg/day, taken in the morning with food. NAD+ is the central cofactor of mitochondrial ATP production; its age-related decline runs in parallel with humanin's. On-mechanism pairing: supporting NAD+ addresses the substrate supply that humanin's cytoprotective signaling operates within.
CoQ10 (ubiquinol form):: 200–400 mg ubiquinol daily with a fat-containing meal (fat-soluble; absorption is poor without it). Coenzyme Q10 carries electrons in the mitochondrial electron transport chain — the same energy apparatus humanin's mito-derived signaling sits atop. Ubiquinol is the reduced, more bioavailable form vs. ubiquinone.

Amplify the machinery — B-vitamins + magnesium

The enzymatic reactions of mitochondrial energy metabolism cannot proceed without B-vitamin cofactors or without magnesium as the carrier of usable ATP.

B-complex (B1, B2, B3, B5, B12):: A quality B-complex once daily with food, covering thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), and B12. These vitamins are rate-limiting cofactors in the TCA cycle and oxidative phosphorylation — the core reactions mitochondria use to produce ATP. Without them the energy chain stalls regardless of what mitochondrial-derived signals are circulating.
Magnesium (glycinate or malate):: 300–400 mg elemental magnesium daily, in the evening. Usable cellular energy is carried as magnesium–ATP; without adequate magnesium the ATP that mitochondria produce cannot be utilized. Magnesium glycinate or malate are better-tolerated forms than oxide.

Mitigate the cost — metabolic baseline + alpha-lipoic acid

Humanin's metabolic and insulin-sensitivity signaling lines up with general mitochondrial health practices; these reduce the background 'noise' that blunts mitochondrial function.

Alpha-lipoic acid (ALA):: 300–600 mg/day, taken with meals. ALA is a mitochondrial antioxidant and insulin-sensitizer that works inside the mitochondrion itself — relevant because humanin's metabolic signaling was characterized in the context of insulin sensitivity. R-ALA is the biologically active enantiomer and is preferred.
Metabolic-health basics:: Exercise (the strongest known stimulus of mitochondrial biogenesis), a low-glycemic whole-food diet, and adequate sleep are the background context that determines mitochondrial function and, by extension, the environment humanin-level signaling operates in. No supplement replaces these for mitochondrial output.

Combinations + timing

Stacking notes + timing windows

Humanin's natural stack partners are the other mitochondrial-derived peptides — MOTS-c and SS-31 — and NAD+ precursors, all hitting mitochondrial biology from a different angle. The rationale is complementary signals on the same system, not the same lever twice. The honesty caveat matters doubly here: humanin's own human evidence is observational and preclinical, so any stack layers an unstudied combination on top of an already-unproven agent.

User combinations reasoned from complementary mechanisms and shared mitochondrial-health biology — not regimens studied head-to-head, and emphatically not in humans. Each partner is individually preclinical or observational; combining them multiplies uncertainty. Doses are community convention; 'reached for' describes usage patterns, not proven indications.

Humanin + MOTS-c

The complementary mtDNA-encoded duo — both peptides are encoded in the mitochondrial genome but signal through distinct pathways.

Why it works:: Humanin is primarily a cytoprotective / anti-apoptotic signal — it prevents cell death. MOTS-c acts more on metabolic signaling and exercise-mimicking pathways (notably AMPK activation and glucose metabolism), a distinct mechanism from humanin's anti-apoptotic / receptor-complex biology. Two different outputs from the same mitochondrial origin. Note: both are observational/preclinical in humans; stacking them is reasoning, not studied synergy.
The protocol:: Humanin 1,000 mcg SC once daily + MOTS-c at its community convention (typically 10–20 mg SC once daily in the morning, though MOTS-c dosing is also convention-only). Same injection session is common — rotate sites.
Outcome:: Reached for in longevity-focused mitochondrial-support stacks where both cytoprotection and metabolic signaling are goals. The honest catch: two unproven signals in combination means no one has any idea what the interaction looks like.

Humanin + SS-31 (elamipretide)

Humanin signals cell survival from outside the mitochondrion; SS-31 stabilizes the mitochondrial membrane from within — structurally complementary.

Why it works:: SS-31 (elamipretide) is a cell-penetrating peptide that targets cardiolipin on the inner mitochondrial membrane, protecting the electron transport chain from oxidative damage and preserving membrane integrity. Humanin acts upstream as a survival signal (anti-apoptotic, cytoprotective). They address different aspects of mitochondrial health: SS-31 maintains the physical structure; humanin modulates the cell-death / survival decision. Complementary levers, not the same one twice.
The protocol:: Humanin 1,000 mcg SC once daily + SS-31 at its community convention (typically 100–200 mcg SC daily or on alternating days; SS-31 has early human trial data in specific cardiac conditions but no validated general-use dose). Rotate injection sites.
Outcome:: Reached for in mitochondrial-support contexts where membrane integrity and cell survival are both goals — particularly in aging and metabolic health framing. SS-31 is further along in human research than humanin, though not in general wellness use.

Humanin + NAD+ precursors (NR / NMN)

The age-parallel stack — humanin levels and NAD+ both decline with aging on a related trajectory; supporting NAD+ addresses the energy substrate humanin's mitochondrial signaling depends on.

Why it works:: NAD+ precursors (nicotinamide riboside or NMN) raise intracellular NAD+ levels, fueling the mitochondrial electron transport chain. Humanin is mitochondria-derived and operates within the same mitochondrial biology. Rather than a receptor-to-receptor synergy, this is substrate supply meeting signaling — the energy chain runs better when NAD+ is adequate, and humanin's cytoprotective signals are part of that system. Non-overlapping mechanisms.
The protocol:: Humanin 1,000 mcg SC once daily + NR 300–500 mg orally with breakfast or NMN 250–500 mg sublingually in the morning. NAD+ precursors are oral supplements; no injection needed. They can run concurrently with humanin without interaction concerns at these doses (though neither combination has been studied).
Outcome:: The most straightforward humanin pairing — adds the best-documented mitochondrial-support intervention (NAD+ precursors have more human data than humanin itself) to the weaker-evidenced mitochondrial signal. The honest frame: NR/NMN have some human trial data; humanin does not — so the 'stack' is mostly the NR/NMN doing verified work while humanin's contribution remains speculative.

Reconstitution math

Reconstitution calculator

Calculated for a 1 mL U-100 insulin syringe (100 units/mL).

Peptide per vial

BAC water added

Desired dose

Units per dose

Draw to this mark on a U-100 syringe

Volume per dose: 0.2 mL
Doses per vial: 10
Concentration: 5 mg/mL

One vial lasts

Daily: 10 days
Every other day: 20 days
5×/week: 14 days

Research use only. Not for human consumption. Outputs are reference values based on research literature — verify all measurements independently.

From the studies

Side effects from research

There is no human safety dataset for humanin — that absence is itself the key fact. No controlled human trials have characterized its tolerability, adverse-event profile, immune reactions, or long-term risk. So no human side-effect profile can be reported.

Being endogenous (made by the body) is not the same as being safe to inject. The body produces humanin at very low physiological concentrations; dosing it from outside at higher levels is a different situation, and the pathways it acts on — apoptosis, IGF, insulin — are biologically powerful, so off-target or systemic effects are plausible but completely uncharacterized in humans.

The honest statement to publish is simply: human safety is unknown, because no clinical safety data exist for administered humanin.

As reported in literature

Research dosing ranges

There is no human dosing table to present, because no human interventional trials of administered humanin exist. The rows below summarize the actual evidence tiers — cell, rodent (mostly the HNG analog), and human observational — so the correlational nature of the human data is never mistaken for a tested treatment. No route, dose, or schedule here should be read as a human regimen.

Dose	Route	Model	Outcome	Sources:
Endogenous / in-vitro	n/a	Cell culture — discovery as a neuronal 'rescue factor'	Abolished neuronal death caused by multiple familial Alzheimer's genes and amyloid-beta — the founding finding (cells, not people)	PMID 11371646
Rodent (HNG analog)	IP / SC	Animal models — neuroprotection, cardiac, metabolic (predominantly HNG)	Protective effects reported, but mostly with the ~1,000× more potent HNG analog — does not transfer cleanly to native humanin	PMID 29043002
Central infusion	ICV (brain)	Rat — central regulation of peripheral insulin action	Hypothalamic action improving whole-body insulin sensitivity (mechanistic rodent study)	PMID 19623253
Observational only	n/a	Human — circulating humanin vs. age (Aging Cell 2014)	Blood humanin DECLINES with age and is regulated by IGF-I — an association, not evidence that restoring it helps	PMID 25040290
Observational only	n/a	Human — cross-sectional cohorts (summarized in reviews)	Higher in long-lived offspring of centenarians; variably associated with metabolic and Alzheimer's status — correlations, not interventional proof	PMID 35499074

Quick answers

Frequently asked

Is humanin a natural part of the body?

Yes. Humanin is an endogenous peptide encoded inside the mitochondrial MT-RNR2 gene — the first mitochondrial-derived peptide ever identified. Your own cells make it. But being natural does not make injecting it proven or safe.

Does humanin slow aging or extend lifespan in people?

There is no human evidence that it does. The human data are observational — humanin levels fall with age and are higher in people who inherit exceptional longevity — which are correlations, not proof. Most of the dramatic anti-aging and protective results are in rodents, and usually with the more-potent HNG analog rather than native humanin.

What is HNG, and why does it matter?

HNG is S14G-humanin, a lab-made analog with a single amino-acid change (serine to glycine at position 14) that makes it roughly 1,000 times more potent and more stable than native humanin. Most striking animal results use HNG — so when a study says 'humanin did X,' it often actually means HNG, not the native peptide a vendor typically sells.

Is there an established dose for humanin?

No. There is no validated human dose, no human dose-finding study, and no human pharmacokinetic data. All dosing in the literature is from rodent studies, mostly using the HNG analog. Any specific milligram 'protocol' is extrapolation without human evidence.

Is humanin banned in sport?

It is not explicitly named on the 2026 WADA Prohibited List, but as a non-approved peptide with growth-factor-like and metabolic signaling activity it would most plausibly fall under the non-approved-substances category (S0), which bans such substances at all times. That is an inference, not a verbatim listing — an athlete should treat it as prohibited and confirm with their anti-doping authority.

Primary sources

References

PMID 11371646Hashimoto et al., PNAS 2001 — discovery of humanin as a neuronal 'rescue factor'
PMID 14561895Ikonen et al., PNAS 2003 — humanin interacts with IGFBP-3 to regulate survival/apoptosis
PMID 19386761Hashimoto et al., Mol Biol Cell 2009 — humanin acts via a CNTFRα/WSX-1/gp130 receptor complex
PMID 19623253Muzumdar et al., PLoS One 2009 — humanin as a central regulator of peripheral insulin action (rat)
PMID 25040290Lee et al., Aging Cell 2014 — IGF-I regulates the age-dependent decline of humanin (human observational)
PMID 29043002S14G-humanin (HNG) analog reference — neuroprotection, Exp Ther Med 2017
PMID 35499074Review — mitochondria-derived peptides in aging and healthspan, J Clin Invest 2022
PMID 32910336Review — mitochondrial-derived peptides in aging and age-related diseases, GeroScience 2021
PubChem CID 16131438PubChem record — formula, MW, sequence
WADA 2026WADA 2026 Prohibited List (humanin not individually named; S0 status by inference)

Research use only · Not medical advice · Updated 2026-06-01