▶ HUMANIN · SUBTOPIC · MECHANISM
HUMANIN Mechanism
For Laboratory Research Use Only. The mechanistic information below is descriptive of published research. No human dose is recommended. No clinical claim is made.
MECHANISM OF ACTION
Twenty-four-amino-acid peptide encoded in the mitochondrial 16S-rRNA (cousin to MOTS-c). Anti-apoptotic via BAX inhibition and neuroprotective in Alzheimer's-disease cell-line models. Discovered by Cohen group 2001 from cDNA library of dying neurons.
PHARMACOKINETIC HALF-LIFE
Reported half-life for HUMANIN: Short (minutes) plasma · longer in CNS. Half-life determines the kinetic window across which receptor occupancy is maintained and frames the dosing rhythm used in published literature.
PRIMARY SEQUENCE
HUMANIN is a defined sequence: Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala (native 24-residue). Synthesis proceeds via solid-phase peptide synthesis with HPLC-verified identity confirmation.
MECHANISTIC OUTCOMES IN LITERATURE
The following outcomes are the mechanistic endpoints reported in the peer-reviewed literature, with GIGARESEARCH evidence grades. Grades reflect study quality and replication, not clinical recommendation.
Hashimoto 2001 demonstrated humanin protects neurons against amyloid-beta toxicity in vitro and in rodent models.
Muzumdar 2009 demonstrated humanin improves insulin action in obese rats.
Circulating humanin levels correlate with longevity in human population studies (Lee et al., 2015).
MECHANISM Q+A
▶ Is there a humanin variant called HNG?
HNG (S14G-humanin) is a synthetic analog with a serine-to-glycine substitution at position 14 that increases potency ~1000-fold in some cell models. It is the variant most commonly used in mechanism studies.
CITED LITERATURE
- Hashimoto Y, Niikura T, Tajima H, et al.. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc Natl Acad Sci U S A 2001. PMID 11371641. link
- Muzumdar RH, Huffman DM, Atzmon G, et al.. Humanin: a novel central regulator of peripheral insulin action. PLoS One 2009. PMID 19470690. link
- Lee C, Zeng J, Drew BG, et al.. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015. PMID 25738459. link
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▶ LAST UPDATED · 2026-05-19