Humanin
Humanin (Mitochondrial-Derived Peptide)
Humanin is a 21-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of mitochondrial DNA, first identified in 2001 as a neuroprotective factor against Alzheimer's disease-related neuronal death. It is studied primarily for its cytoprotective, anti-apoptotic, and metabolic-regulating properties, with research interest spanning neuroprotection, cardiovascular health, insulin sensitivity, and longevity. Circulating humanin levels decline with age, making it a candidate biomarker and potential therapeutic target in aging and age-related diseases.
Mechanism of Action
Humanin exerts its effects primarily by binding to a trimeric receptor complex composed of CNTFR, WSX-1, and gp130, activating downstream JAK2/STAT3 and PI3K/Akt signaling pathways that suppress apoptosis and promote cell survival. It also binds intracellularly to the pro-apoptotic protein BAX, preventing its mitochondrial translocation and subsequent cytochrome c release, thereby blocking intrinsic apoptotic cascades. Additionally, humanin acts as an insulin sensitizer by modulating hepatic glucose output and improving peripheral glucose uptake via FPRL1/FPR2 receptor interactions, contributing to its metabolic and cytoprotective effects.
Evidence by Health Goal(17 goals)
Dosing Protocols
Morning, preferably on an empty stomach or post-fasting
Cycle: 8-12 weeks on, 4 weeks off
Subcutaneous injection is the most common route in research settings. Lower doses (100-200mcg) are used for general cytoprotection and metabolic support; higher doses (300-500mcg) explored for neuroprotective applications. No established clinical dosing exists; protocols are extrapolated from preclinical and early human studies.
Morning on an empty stomach
Cycle: 8-12 weeks on, 4 weeks off
Intranasal delivery is explored to facilitate CNS penetration for neuroprotective applications, bypassing the blood-brain barrier more effectively than peripheral injection. Bioavailability via this route is less characterized than subcutaneous injection.
Safety & Side Effects
Humanin has demonstrated a favorable safety profile in preclinical animal studies and limited human research, with no serious adverse events reported at physiological replacement doses; however, long-term safety data in humans is insufficient and clinical trials are still in early stages. It is not an approved pharmaceutical in any jurisdiction, and is available only as a research peptide, meaning quality, purity, and dosing accuracy depend heavily on vendor reliability.
Possible Side Effects
- !Injection site irritation, redness, or mild swelling with subcutaneous administration
- !Transient hypoglycemia or blood glucose fluctuations, particularly in insulin-sensitive individuals
- !Mild fatigue or lethargy reported at higher doses in some users
- !Nasal mucosal irritation or rhinorrhea with intranasal administration
- !Potential headache reported anecdotally at initiation
- !Theoretical immunomodulatory effects with long-term use not yet fully characterized
Interactions
- -May potentiate hypoglycemic effects of insulin or oral antidiabetic agents (e.g., metformin, sulfonylureas) - monitor blood glucose closely
- -Theoretical additive cytoprotective effects when combined with other mitochondrial-targeting compounds such as MitoQ or SS-31 peptides
- -May enhance neuroprotective effects of acetylcholinesterase inhibitors used in Alzheimer's disease treatment - combination effects unstudied in humans
- -Potential interaction with anticoagulant or antiplatelet therapies due to reported effects on platelet aggregation pathways - use caution
- -Concurrent use with growth hormone or IGF-1 axis compounds may amplify metabolic effects - combination protocols lack safety data
Cost & Where to Buy
Research-grade humanin peptide is available from specialty peptide vendors at approximately $30-80 per vial (typically 1-5mg lyophilized). Monthly cost depends heavily on dose frequency and vendor; higher-purity pharmaceutical-grade preparations command premium pricing. No pharmaceutical-grade humanin is commercially approved, so all sources are research chemical vendors with variable quality control.
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