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Humanin

Humanin · HN

C
Animal replicated
Research chemicalMitochondrial-Derived PeptideCytoprotective PeptideMDP
RouteInjectableGray-market only
C
Evidence grade: Animal replicated

Effect demonstrated in multiple animal studies; human data sparse or extrapolated. Grades summarize evidence quality, not whether a compound is appropriate, legal, or risk-free.

At a glance
What it is
MAPRGFSCLLLLTSEIDLPVKRRA — Mitochondrial-Derived Peptide (MDP) — Mitochondrial-Derived Peptide, Cytoprotective Peptide, MDP.
Why people use it
Neuroprotection · Cognitive Function and Brain Aging · Longevity and Healthspan · Cardiovascular Protection · Metabolic Effects · Cancer
What the evidence supports
Observational/correlative only. No human intervention trial for any indication. Human data: plasma decline with age confirmed; centenarian offspring correlation confirmed; IGF-1 inverse relationship confirmed in GH-deficient children and Laron Syndrome cohorts; lower levels documented in Alzheimer's disease and MELAS patients. No RCT. No open-label trial. All intervention data is animal (mouse, C. elegans).
If you only read one thing

Humanin levels decline with age. Children of centenarians have higher Humanin levels than age-matched controls. Animals with mutations that extend lifespan have elevated Humanin. These correlations are among the most compelling longevity biomarker findings in the aging literature. The community has responded by supplementing with Humanin/HNG. What the community has generally not processed: Humanin and IGF-1 are inversely regulated. GH treatment drops plasma Humanin by ~20% in humans. Laron Syndrome patients — who have GH receptor deficiency, extremely low IGF-1, and virtually no cancer — have 80% HIGHER Humanin than matched controls. The community routinely uses GH secretagogues (CJC-1295, Ipamorelin) to raise GH and IGF-1 for anti-aging purposes. Those same interventions likely suppress Humanin. If Humanin is a genuine longevity signal and not merely a correlate, the most popular anti-aging peptide protocol in the community may be working against the very mitochondrial signal that predicts longevity. This tension has not been resolved. It needs to be understood before any protocol decision is made.

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Published literature
0human trials0human studies0animal0in vitro
Evidence reality check
Human evidence
No human studies
0 observational; RCT evidence not present in corpus.
Preclinical base
0 lab signals
0 animal; 0 in-vitro/mechanistic.
Best-supported use
Aβ neuroprotection (in vitro)
A grade · Humanin/HNG protects neurons from Aβ toxicity; FPR2 + Bax + IGFBP-3 mechanisms confirmed. Cell culture; not in vivo human neurons; Alzheimer's drug pipeline history cautionary
Indication map
Supported / plausible / speculative / avoid
Supported
Aβ neuroprotection (in vitro)
A grade · Humanin/HNG protects neurons from Aβ toxicity; FPR2 + Bax + IGFBP-3 mechanisms confirmed. Cell culture; not in vivo human neurons; Alzheimer's drug pipeline history cautionary
Supported
Neuroprotection in animal models
B grade · Reduces Aβ burden; protects from ischemia; prevents AD-related apoptosis in mice. Animal; no human AD trial
Supported
Cognitive aging prevention
B grade · HNG twice weekly prevented age-related cognitive decline across multiple behavioral tests. Single group; aging mice; no human RCT
Supported
Longevity correlation (human observational)
B grade · Centenarian offspring have higher Humanin; naked mole-rat levels stable; age-related decline confirmed. Observational; correlation not causation; Cohen group primary

Humanin is the mitochondrial peptide that told us mitochondria are endocrine organs. Its discovery was more revolutionary than its community discourse reflects. The longevity correlations are among the most compelling in aging biology. And the IGF-1 inverse relationship is the most consequential underappreciated fact in the longevity peptide space.

The central tension resolved: Humanin levels decline with age in every species studied. People whose parents and grandparents lived to 100+ have more of it than their peers. The longest-lived mammal (naked mole-rat) maintains it throughout its exceptional lifespan. People with genetic mutations that suppress IGF-1 — who have low cancer rates and extended healthspan — have 80% more of it. And the compound that produced the highest circulating levels in a human intervention wasn't longevity-focused at all: it was GH treatment, which drops Humanin by ~20%. The standard community GH secretagogue protocol likely suppresses endogenous Humanin. Whether this matters, and whether exogenous HNG compensates for it, is the most important unanswered protocol question in the mitochondrial longevity stack.

The strongest argument for Humanin: the evidence architecture is more distributed than most longevity compounds. Neuroprotection against Aβ has been confirmed in multiple independent labs across multiple countries. The cardiovascular correlation is from the Mayo Clinic, not Cohen's group. The metabolic data is from Barzilai's group at Einstein. The longevity correlation is from Cohen's group but uses multiple independent species and human cohort designs that are methodologically credible. The C. elegans lifespan extension is well-documented and autophagy-dependent — one of the most conserved longevity pathways in biology. Humanin is not a Khavinson-type single-source compound.

The strongest argument for caution: no human intervention trial exists. The centenarian correlation is compelling but observational. The IGF-1 inverse relationship makes the pharmacological context of supplementing HNG in a high-IGF-1 environment (GH secretagogue users) different from the low-IGF-1 environment where high Humanin is associated with longevity. And the IGFBP-3 neutralization mechanism creates a theoretical cancer concern that is different in character depending on the IGF-1 context.

Categories
Cognition & MoodLongevity & Anti-agingMitochondrial & Energy
Properties
Active malignancy: hard stopWADA S4Not injectable
Evidence
CAnimal replicated
The Discovery Context
Discovered in 2001 by Nishimoto et al. during a screen for genes that protect neurons from Alzheimer's disease-relevant insults. The cDNA library screened was derived from the occipital cortex of an Alzheimer's patient — the brain region that survived the disease while surrounding areas were destroyed. 'Humanin' was named to reflect this survival.
Why It Matters — The Paradigm Shift
Humanin's discovery established that the mitochondrial genome — long thought to encode only 13 ETC proteins, 22 tRNAs, and 2 rRNAs — also produces secreted signaling peptides. This reframed mitochondria as endocrine organelles. Humanin, MOTS-c, and the SHLP family are all encoded in the same mitochondrial RNA region.
The HNG Analog — What Actually Gets Used
Native Humanin is weakly potent at practical doses. The synthetic analog HNG (S14G-Humanin, also called Humanin-G) — where serine at position 14 is replaced by glycine — is 1,000 to 10,000 times more potent than native Humanin and is used in most animal research. Most commercial research peptide vendors sell HNG rather than native Humanin. This is the compound most community users are actually taking.
The Centenarian Connection
Cohen et al. (Aging, 2020): children of centenarians (who are themselves more likely to become centenarians) have significantly higher circulating Humanin levels than age-matched controls without long-lived parents. Additionally, naked mole-rats — a model of negligible senescence with dramatically extended lifespan — maintain stable Humanin levels throughout their long lives, unlike other species where Humanin declines progressively with age.
THE IGF-1 INVERSE — THE COMMUNITY'S BLIND SPOT
Humanin and IGF-1 are inversely regulated: IGF-1 suppresses Humanin. GH treatment in GH-deficient children reduced plasma Humanin by ~20%. Laron Syndrome patients (GH receptor deficiency, very low IGF-1, virtually no cancer) have 80% HIGHER Humanin than matched controls. The community widely uses GH secretagogues (CJC-1295, Ipamorelin) to raise GH/IGF-1. Those same interventions likely suppress Humanin. If Humanin is a longevity signal — and the centenarian data suggests it is — the community's standard GH protocol may be working against its own longevity goals.
Animal Evidence
HNG extends lifespan in C. elegans via daf-16/FOXO (Cohen group). Humanin transgenic mice have extended healthspan phenotypes. HNG prevents age-related cognitive decline in aging mice (Scientific Reports 2018). Multiple independent labs document neuroprotection against Aβ toxicity, ischemia, and oxidative stress.
Community Dosing
0.5-2 mg HNG (or native Humanin) subcutaneously, typically weekly rather than daily. Cycling standard. Doses are empirical extrapolations from animal studies; no validated human dose exists.
FDA / Regulatory
Not FDA-approved. Not PCAC-reviewed. Research chemical only. Not a controlled substance.
WADA
Not currently listed on the 2026 WADA Prohibited List. Unlike MOTS-c (S4.4 explicitly named), Humanin/HNG has not been specifically added to the banned list as of May 2026. Verify current status before competition use.
Primary Research Group
Pinchas Cohen, USC Davis School of Gerontology. His group discovered most of the key Humanin/aging findings. Unlike many compounds in this reference, substantial independent replication exists in the neuroprotection literature from Japanese groups (Nishimoto, Hashimoto), US cardiology groups, and others — though the aging/longevity evidence is more Cohen-concentrated.
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Alternatives

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SHLP2
C
Same class · Mitochondrial-Derived Peptide

The Metabolically Active Member of a Six-Peptide Family From the Same Mitochondrial Gene as Humanin. A Receptor Has Been Found. An Obesity Protection Mechanism Has Been Identified. Lower Levels Are Associated With Prostate Cancer Risk. No Human Trial Has Been Run.

SHLP6
C
Same class · Mitochondrial-Derived Peptide

Every Other MDP in this reference Keeps Cells Alive. SHLP6 Tells Them to Die. This May Be Exactly the Point — and the Most Underappreciated Mechanism in the Entire Mitochondrial Peptide Family.

MOTS-c
C
Same class · Mitochondrial-Derived Peptide

Mitochondrial-derived peptide studied for AMPK signaling, metabolic stress resilience, and exercise-mimetic pathways.

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