Humanin
Humanin was the first recognised mitochondrial-derived peptide, encoded within the mitochondrial 16S rRNA gene. It has been investigated preclinically for neuroprotection (particularly against amyloid-beta toxicity), insulin sensitivity and cardioprotection, and more-potent analogues such as HNG have been studied in the laboratory. Human data are essentially observational (for example, circulating humanin levels), there are no completed controlled efficacy trials, and it remains experimental.
Mechanism
In plain terms, humanin appears to act as a survival signal that helps cells resist stress and programmed death. Technically, it is an approximately 24-amino-acid peptide encoded in mitochondrial DNA that acts both inside and outside the cell: it can bind and inhibit the pro-apoptotic protein Bax and interact with related proteins, and extracellularly it is reported to signal through a trimeric receptor complex (formyl-peptide-receptor-like-1 and the CNTFR/WSX-1/gp130 receptor) to activate cytoprotective pathways such as STAT3. These mechanisms are established mainly in cell and animal models.
Regulatory Status by Region
- United States (FDA)Not FDA-approved; a research/experimental peptide with no approved therapeutic use.
- Australia (TGA)Not on the ARTG; an unapproved experimental substance.
- European Union (EMA)No EMA marketing authorisation; not an approved medicine in the EU.
- WADANot listed by name on the Prohibited List; as a non-approved substance, athletes should verify current status with their anti-doping organisation.
Key Studies
- A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta (Hashimoto Y, Niikura T, Tajima H, et al. Proc Natl Acad Sci U S A. 2001;98(11):6336-6341. PMID 11371646)
- Humanin peptide suppresses apoptosis by interfering with Bax activation (Guo B, Zhai D, Cabezas E, et al. Nature. 2003;423(6938):456-461. PMID 12732850)