Humanin

Typical use cases

Dosing guidelines

Titration

Reported community practice begins at a low dose (e.g., ~0.5 mg weekly) and adjusts based on subjective response; commonly run in 4-8 week cycles with 2-4 week breaks, often 2-4 cycles per year. These are reported patterns, not recommendations.

Reconstitution

Lyophilized powder reconstituted with bacteriostatic water; e.g., a 5 mg vial with 1 mL yields 5 mg/mL. Add diluent slowly down the vial wall and swirl gently rather than shaking; typically drawn with U-100 insulin syringes.

Injection sites

Subcutaneous injection, typically into the abdomen (avoiding the navel) or other subcutaneous fat sites

Storage & handling

Lyophilized vials stored refrigerated at 2-8°C (long-term may be frozen); once reconstituted, kept at ~2-8°C and typically used within roughly 4-6 weeks. Avoid repeated freeze-thaw cycles and protect from light.

Side effects

• Injection-site irritation, redness, or discomfort Mild · Common
• Transient fatigue Mild · Uncommon
• Headache Mild · Uncommon
• Changes in blood glucose / insulin sensitivity (relevant alongside insulin or sulfonylureas) Moderate · Uncommon
• Allergic / hypersensitivity reaction Severe · Rare
• Theoretical anti-apoptotic (BAX-inhibition) effect potentially protecting abnormal cells Moderate · Rare

Research summary

Humanin (HN) was identified in 2001 as the first mitochondrial-derived peptide (MDP), encoded within a short open reading frame in the mitochondrial 16S rRNA (MT-RNR2) gene. The evidence base is predominantly preclinical. In cell and animal models, humanin shows broad cytoprotection against amyloid-beta toxicity, oxidative stress, serum starvation, hypoxia, and ischemia/reperfusion injury, acting through both intracellular mechanisms (binding and inhibition of pro-apoptotic proteins such as BAX, and interaction with IGFBP-3) and extracellular receptor signaling (FPRL1/FPRL2 formyl-peptide receptors and a tripartite gp130/CNTFR/WSX-1 cytokine-like receptor complex that activates AKT, ERK1/2, and STAT3). Longevity-relevant findings include lifespan extension when humanin is overexpressed in C. elegans and improved metabolic parameters in mid-life HNG-treated mice, alongside human correlative data showing that circulating humanin tends to decline with age, is reported lower in Alzheimer's CSF, and has been found elevated in offspring of centenarians. The potent synthetic analog HNG (humanin-S14G, a glycine substitution at serine-14) is reported in preclinical work to be substantially more neuroprotective than native humanin and is the form in most research/community products. Key limitations are the near-total absence of controlled human clinical trials, native humanin's very short plasma half-life, uncertain optimal dosing, and a theoretical concern that anti-apoptotic (BAX-inhibiting) activity could in principle protect abnormal cells.

Key references

• https://pmc.ncbi.nlm.nih.gov/articles/PMC7343442/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC3705736/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC3641182/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC5216912/
• https://pmc.ncbi.nlm.nih.gov/articles/PMC5549471/

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