Humanin

The Humanin evidence base cited here is 7 sources — 5 preclinical, 2 review. Critically, that evidence is almost entirely preclinical (animal and in-vitro) — no human clinical trials are cited, so efficacy and safety in people remain unproven. Regulatory status: Not FDA-approved.

• Humanin is a 21-amino-acid peptide encoded within the mitochondrial 16S rRNA region and first identified in 2001 as a neuroprotective factor from surviving neurons in Alzheimer's disease brains; circulating humanin levels decline with age across species, and children of human centenarians show substantially elevated humanin compared to age-matched controls.
• Mechanistically, humanin binds IGFBP-3 and blocks amyloid-beta aggregation; in the presence of IGFBP-3 the protective interaction with Aβ is abolished and amyloid oligomer formation increases, identifying IGFBP-3 as a physiological regulator of humanin's neuroprotective capacity and a potential Alzheimer's disease risk modifier.
• Humanin activates chaperone-mediated autophagy (CMA) by enhancing substrate-binding and lysosomal translocation via HSP90 interaction, and also triggers ERK1/2, AKT, and STAT3 signaling pathways — providing mechanistic underpinning for its cardioprotective, neuroprotective, and metabolic effects.

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