Humanin

Humanin was discovered in 2001 in a search for factors that protect neurons from amyloid-beta toxicity — the first of the mitochondrial-derived peptides to attract serious attention. It is twenty-four amino acids long, produced inside mitochondria and found in circulation, with levels that decline with age and change with metabolic disease. Preclinical work has since described cytoprotection in many cell types, metabolic effects in rodents and protection of the heart after ischaemia. The important distinction for readers is between humanin as an endogenous signalling peptide and humanin as a product: the clinical work that exists used a modified analogue, and circulating-level correlations are not the same as injecting the peptide.

Humanin acts through multiple routes rather than a single receptor, including the formyl peptide receptor-like 1 and, in some contexts, the IGF-1 receptor and STAT3 pathway. Its best-characterised effect is interference with apoptosis — it blocks the cellular self-destruct programme under stress — alongside reduced oxidative stress and improved mitochondrial function. It also behaves as a metabolic regulator, improving insulin sensitivity and reducing fat accumulation in rodents. The analogue HNG was engineered for greater potency and stability.

• Blocks apoptosis and reduces oxidative stress in many cell models
• Improved insulin sensitivity and reduced fat mass in rodent studies
• Improved cardiac function after ischaemia-reperfusion in animal models
• Circulating humanin levels correlate with metabolic and cognitive health in human cohorts

Reported benefits describe what the published literature and user reports suggest — not a promise of outcome for any individual.

Preclinical evidence for humanin is broad: neuroprotection, cardiac protection, metabolic improvement and reduced inflammatory signalling have all been shown in cell and animal models. Human evidence is narrower. Cohort studies associate higher circulating humanin with better metabolic and cognitive measures, and a synthetic analogue reached early-phase human testing in Alzheimer's disease with acceptable short-term tolerability but no demonstrated clinical benefit. That is the whole evidence base. Everything sold as humanin for self-injection is being used far beyond it, with no pharmacokinetic data, no dose-finding studies and no long-term safety record.

• No human adverse-event data for injected humanin
• Injection-site reactions and sterility risks of reconstituted powder
• Unknown effects of long-term administration

No human safety data. Because humanin influences apoptosis and interacts with growth-factor signalling, chronic administration is a theoretical concern as well as an unquantified one. The peptide sold by suppliers is also not necessarily characterised against the natural sequence, which matters more than usual for a molecule whose action depends on specific residues.

Not studied in combination with anything. It is often listed alongside other mitochondrial-derived peptides such as MOTS-c, which only compounds unverified interventions.