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Humanin: Complete Guide

Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded in the mitochondrial genome (16S rRNA gene). Discovered in 2001 as a survival factor for neurons exposed to Alzheimer's disease-related insults, humanin has since been found to have broad cytoprotective, anti-apoptotic, and metabolic regulatory properties. Along with MOTS-c, it represents a growing class of mitochondrial peptides that function as retrograde signaling molecules.

Last updated: 2026-01-29

Quick Facts

Category
therapeutic
Also Known As
HN, HNG
Related Goals
anti aging

Who Researches Humanin?

Humanin is researched by people interested in anti-aging at the cellular level, particularly through mitochondrial-derived peptide signaling. It's relevant for researchers studying neuroprotection (Alzheimer's, stroke), metabolic health (insulin sensitivity, diabetes), and longevity biology. Humanin is often discussed alongside MOTS-c — another mitochondrial-derived peptide — as part of the emerging field of mitochondrial retrograde signaling. Those interested in why aging mitochondria drive systemic decline will find humanin research foundational.

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What Is Humanin?

Humanin was discovered by Nishimoto and colleagues in 2001 while screening for factors that protect neurons against amyloid-beta toxicity — the protein aggregates associated with Alzheimer's disease. Unexpectedly, the protective factor was encoded not in the nuclear genome but in the mitochondrial genome, within the 16S ribosomal RNA gene.

This was a conceptually revolutionary finding: mitochondria — the cell's energy-producing organelles — were producing signaling peptides that regulate cell survival and metabolism. Humanin became the founding member of the mitochondrial-derived peptide (MDP) family, which now includes MOTS-c, SHLPs, and other peptides encoded in mitochondrial DNA.

Mechanism of Action

Humanin acts through multiple pathways:

  • FPRL1/FPRL2 receptors: Activates formyl peptide receptor-like receptors, triggering anti-apoptotic signaling cascades
  • IGFBP-3 interaction: Binds IGF binding protein-3, modulating IGF-1 signaling and cell survival
  • BAX inhibition: Directly binds pro-apoptotic protein BAX, preventing mitochondrial outer membrane permeabilization and apoptosis
  • STAT3 signaling: Activates STAT3 pathway for anti-inflammatory and cell survival effects
  • Metabolic effects: Improves insulin sensitivity and glucose homeostasis through central and peripheral mechanisms

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Dosage Overview

Humanin research dosing varies widely by application and analog used. The synthetic analog HNG (S14G-humanin) is 1,000x more potent than native humanin. Animal studies typically use 0.1–4 mg/kg IP or SC. Human dosing protocols are not standardized as no clinical trials with humanin have been completed to date.

For injectable research preparations, standard peptide reconstitution with bacteriostatic water applies. Use the peptide calculator for reconstitution volumes.

Side Effects & Safety

  • Limited safety data: Most research is preclinical (cell culture and animal models)
  • Endogenous peptide: As a naturally produced mitochondrial peptide, humanin is expected to have favorable biocompatibility
  • No reported toxicity: Animal studies have not reported significant adverse effects
  • Theoretical concerns: Long-term anti-apoptotic signaling could theoretically affect cancer surveillance, though no evidence supports this concern currently

Frequently Asked Questions

References

  1. Hashimoto Y, et al.. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ. Proceedings of the National Academy of Sciences, 2001.
  2. Lee C, et al.. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 2015.

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Peptides Insider Editorial Team

Our content is reviewed for accuracy and grounded in peer-reviewed research where available. We do not provide medical advice. Always consult a qualified healthcare professional.