Humanin

Humanin is a 21-amino acid peptide encoded within the mitochondrial 16S rRNA gene — making it a mitochondria-derived peptide (MDP) rather than a nuclear-DNA-encoded protein. It is secreted by cells under stress and acts as an endocrine, paracrine, and autocrine signalling molecule. Humanin binds to multiple receptors including the tripartite receptor complex (CNTFR, WSX-1, GP130) and formyl peptide receptor-like-1 (FPRL1), activating downstream survival signalling pathways (STAT3, PI3K/Akt) that protect neurons from amyloid-beta toxicity, oxidative stress, and apoptosis. It also improves insulin sensitivity by reducing hepatic glucose production. Blood Humanin levels decline significantly with age and are lower in individuals with Alzheimer's disease, type 2 diabetes, and cardiovascular disease.

Discovered in 2001 by Nishimoto et al. while screening for peptides that protect neurons from amyloid-beta toxicity — the hallmark of Alzheimer's disease. Subsequent research established its broader role as a mitochondria-derived anti-ageing peptide. A landmark study by Cohen et al. (Cell Metabolism, 2023) demonstrated that Humanin levels in centenarians (individuals living past 100 years) are significantly higher than age-matched controls who did not achieve extreme longevity, and that Humanin administration extended lifespan and healthspan in C. elegans and mouse models. Epidemiological data from the USC Longevity Institute shows inverse correlation between blood Humanin levels and cardiovascular disease and diabetes incidence. Human intervention trials are underway but not yet published. Among the most scientifically compelling emerging longevity targets.

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