Humanin is a 24-amino-acid peptide encoded within the mitochondrial genome, first identified in 2001. Research is mostly cell and rodent work, often using the more potent analog HNG (S14G).
Humanin acts both inside the cell and as a secreted signal. Established findings include binding to the pro-apoptotic protein BAX and to IGFBP-3, and signaling through the FPRL1 (FPR2) receptor and a CNTFR/WSX-1/gp130 receptor complex that activates JAK2/STAT3 [4]. In C. elegans, lifespan effects of humanin overexpression depended on daf-16/FOXO, suggesting links to insulin/IGF signaling; how these pathways translate to mammals is still proposed rather than established [3].
| Study | Model | Reported result | Source |
|---|---|---|---|
| Discovery of humanin [1] | Cell Neuronal cell-death assays with familial-mutation genes and amyloid-beta | Identified via functional expression screening; the secreted peptide blocked neuronal cell death from multiple insults but not from mutant SOD1 or Q79. | Peer-reviewed PNAS 2001 |
| HNG in aging mice: cognition [2] | Mouse Female C57BL/6N mice, HNG from 18 months of age, tested at 24 and 28 months | Researchers measured better Barnes maze and Y-maze performance, fewer activated hippocampal microglia, and lower circulating inflammatory markers vs controls. | Peer-reviewed Sci Rep 2018 |
| Lifespan and healthspan [3] | Mouse Female C57BL/6N mice given HNG from 18 months for 14 months; C. elegans overexpression | Mice: lower visceral fat, higher lean mass, lower IGF-I, no lifespan difference. Worms: mean lifespan 19.0 vs 17.7 days, daf-16 dependent. | Peer-reviewed Aging (Albany NY) 2020 |
| Intranasal humanin in neurotoxin models [5] | Mouse MPTP neurotoxin and α-synuclein transgenic mouse models; SH-SY5Y and primary neurons | Labeled humanin reached mouse midbrain within 30 minutes; researchers measured neuron survival and mitochondrial function markers. | Peer-reviewed Theranostics 2023 |
| HNG in an atrial remodeling model [6] | Mouse Angiotensin II infusion model, male C57BL/6J mice; rat cardiomyocytes and fibroblasts | HNG reduced arrhythmia inducibility and atrial fibrosis, lowered Drp1/Fis1, IL-1β and IL-6, and reduced oxidative stress in cultured cells. | Peer-reviewed Biomedicines 2026 |
| Systematic review [4] | Review Systematic review of humanin in aging research | Summarizes receptor signaling, BAX and IGFBP-3 interactions, and age-related changes in circulating humanin. | Peer-reviewed Biology (Basel) 2023 |
Human trials are listed for research context only; outcomes are reported in the linked publications. Animal and lab results do not establish effects in humans.
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