Abstract
Humanin is a 21-24 amino acid micro-peptide encoded within the mitochondrial 16S rRNA gene. It is expressed in tissues with high metabolic demand and has been studied for its role in cytoprotection and cellular survival pathways.
Molecular Background
- Human sequence (24 aa): MAPRGFSCLLLLTSEIDLPVKRRA
- HNG analog: S14G substitution with reported increased potency
- Forms: Both secreted (circulating) and intracellular (mitochondrial/nuclear)
- Origin: First member of mitochondrial-derived peptide (MDP) family
Research Applications
- Cytoprotection Studies: Anti-apoptotic pathway research
- Metabolic Research: Insulin sensitivity and glucose metabolism
- Cardiovascular Research: Cardioprotection models
- Neuroscience: Neuroprotection and cognitive studies
- Aging Biology: Longevity correlation studies
Proposed Mechanisms
- Receptor Complex: Trimeric receptor (gp130-CNTFR-WSX-1) activation
- JAK2/STAT3 Pathway: Survival signaling activation
- Bax/Bid Inhibition: Direct binding preventing mitochondrial translocation
- IGFBP-3 Binding: Modulation of IGF-1 signaling
Age-Related Observations
Research has documented declining Humanin levels with age in various tissues. Observational studies have noted correlations between circulating Humanin levels and longevity phenotypes.
Preclinical Research
Published studies have examined Humanin in:
- Cardiovascular disease models
- Alzheimer's disease models
- Diabetes and metabolic disorder models
- Naturally aged animal studies
Current Research Status
Humanin has been independently validated across multiple laboratories, distinguishing it from some other bioregulator peptides. Human data remain primarily observational, with no interventional trials published as of December 2025.