Humanin
Also known as: HN, MTRNR2
Humanin is a 24-amino-acid mitochondrial-derived peptide that limits stress-induced apoptosis by binding pro-apoptotic proteins (BAX, Bid/Bim) and IGFBP-3 intracellularly and by signaling extracellularly through FPR2/FPRL1 and the CNTFR/WSX-1/gp130 complex to activate JAK2/STAT3, ERK1/2 and AKT survival pathways.
- Drug class
- Mitochondrial-derived peptide (cytoprotective/anti-apoptotic signaling peptide)
- Primary targets
- FPR2/FPRL1, FPRL2, CNTFR/WSX-1/gp130 receptor complex, BAX, IGFBP-3
- Dose reference
- Research-only; no validated or approved human dose. Preclinical studies typically use the potent analog HNG (S14G-humanin) in animal models (e.g., microgram-to-milligram-per-kg, intermittent injection) - these are experimental figures, not human dosing recommendations.
- Half-life
- Not formally characterized in humans; native humanin is reported to clear rapidly, and engineered analogs such as HNG were developed for greater stability and potency.
- Developer / origin
- Identified in 2001 by the Hashimoto/Nishimoto laboratory, Keio University School of Medicine (endogenous peptide; no commercial developer)
- Reference year
- 2001
- Evidence score
- 2/5 - Preclinical and observational only; no human therapeutic trials
Preclinical and observational only; no human therapeutic trials
Humanin has substantial mechanistic and preclinical evidence for cytoprotection, anti-apoptosis, neuroprotection and metabolic effects in cell and animal models, plus observational human biomarker associations linking endogenous levels to aging and longevity. However, there are no published randomized controlled human trials of humanin or its HNG analog as a therapy, and it has no regulatory approval, so therapeutic human evidence is essentially absent.
Mostly animal, ex vivo, cell, or indirect evidence.
Evidence basis
- Original 2001 PNAS discovery showing rescue of neuronal death from familial Alzheimer's mutations and amyloid-beta
- Mechanistic studies identifying FPR2/FPRL1 and CNTFR/WSX-1/gp130 receptor signaling and IGFBP-3/BAX interactions
- Structural (Nat Commun 2022) and review evidence (J Mol Endocrinol 2013; Front Cell Dev Biol 2022)
- Rodent and primate data plus human observational associations (centenarian offspring, cognitive aging) indicating circulating humanin declines with age and correlates with longevity
- Absence of any registered/published human RCT and no FDA or other regulatory approval
Key references
- PubMedA rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta (PNAS, 2001)
- Nature CommunicationsStructural basis of FPR2 in recognition of Abeta42 and neuroprotection by humanin (Nat Commun, 2022)
- PMCThe emerging role of the mitochondrial-derived peptide humanin in stress resistance (J Mol Endocrinol, 2013)
- PMCThe mitochondrial derived peptide humanin is a regulator of lifespan and healthspan (Aging, 2020)
How to read this entry
Dose references and half-life values are pulled from trial protocols, labels, reviews, or published summaries where available. They are context for research and comparison, not a personal dosing recommendation.
Status matters: approved drugs have regulated indications; investigational compounds are still being studied; research-only peptides do not have established human dosing, safety, or efficacy for consumer use.
Humanin guides
Read the matching guide or adjacent research pages for more context.
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