Humanin

Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of the mitochondrial genome. It was discovered in 2001 from a cDNA library of a surviving neuron in an Alzheimer's disease brain — a cell that had resisted the neurodegeneration surrounding it. This origin is significant: Humanin was identified because of its neuroprotective function, and subsequent research has expanded its role to encompass cytoprotection across virtually every tissue type studied. Along with MOTS-c, Humanin is a founding member of the mitochondrial-derived peptide class.

Humanin exerts its cytoprotective effects through multiple receptor-mediated pathways. It binds to the heterotrimeric receptor complex composed of CNTFR (ciliary neurotrophic factor receptor), WSX-1 (IL-27 receptor subunit), and gp130, activating the JAK2-STAT3 signaling cascade that promotes cell survival and inhibits apoptosis. Humanin also binds to FPRL-1 (formyl peptide receptor-like 1) and the intracellular protein IGFBP-3, modulating IGF-1 signaling. Its anti-apoptotic mechanism involves direct interaction with pro-apoptotic members of the Bcl-2 family (particularly Bax and Bid), preventing their oligomerization at the mitochondrial membrane and blocking the intrinsic apoptotic cascade. Additionally, Humanin reduces endoplasmic reticulum stress, inhibits amyloid-beta toxicity, and modulates inflammatory signaling.

The research literature on Humanin spans neuroprotection, cardioprotection, metabolic regulation, and cellular aging. Studies demonstrate protection against Alzheimer's amyloid-beta toxicity, preservation of cardiac function in ischemia-reperfusion models, improved insulin sensitivity, reduced atherosclerotic plaque formation, and enhanced cellular stress resistance. Circulating Humanin levels decline with age and correlate inversely with age-related disease markers, suggesting endogenous Humanin depletion as a component of the aging process. Notably, centenarians and their offspring have been found to have higher circulating Humanin levels than age-matched controls, establishing an epidemiological link between Humanin and exceptional longevity.

Humanin is suited for researchers investigating neuroprotection, cytoprotection, cellular aging, mitochondrial signaling, and anti-apoptotic mechanisms. It is an emerging cornerstone of multi-pathway longevity protocols and represents the neuroprotective arm of mitochondrial-derived peptide research.

Reconstitute the 5mg vial with 1ml bacteriostatic water (yielding 5mg/ml). Administer via subcutaneous injection, typically 1-5mg per dose, 3-5 times per week. Humanin has a relatively short plasma half-life (approximately 30 minutes for native Humanin), though synthetic analogs with extended half-lives exist in the research literature. Daily or every-other-day dosing supports sustained cytoprotective signaling. Store at 2-8C after reconstitution. Lyophilized powder should be stored at -20C. Humanin is sensitive to oxidation; protect reconstituted solution from prolonged light exposure.

---

## Beauty & Skin