24AA Animal Models
Humanin
The mitochondrial longevity signal — a 24AA peptide encoded inside mitochondrial DNA that declines with age and protects neurons, heart, and metabolic tissues from cell death.
In Plain English:
Humanin is a tiny peptide your own mitochondria produce to protect cells from dying. Discovered in 2001 in the brain of an Alzheimer's patient, it acts as a survival signal across many tissues — blocking the proteins that trigger cell death, dampening inflammation, and improving insulin sensitivity. Your levels drop roughly 40% as you age; centenarians' children have significantly more of it than peers. In animals, it reduces Alzheimer's plaques, halves heart-attack damage, and extends lifespan in worms. Human clinical trials have not yet been conducted.
Research Maturity
Animal Models (540 results on PubMed for 'humanin' (verified 2026-05-04)+ Studies)
Focus
Cellular Protection
Metabolic Health
Neuroprotection
Origin
Discovered 2001 by Hashimoto et al. at KEIO University (Tokyo) via functional screening of an Alzheimer's disease brain cDNA library. Encoded by a short open reading frame (sORF) within the 16S ribosomal RNA gene (MT-RNR2) of the mitochondrial genome — making it a founding member of the mitochondrial-derived peptide (MDP) family. Endogenous levels decline with age across humans, mice, and primates; naked mole-rats, which show negligible senescence, maintain stable humanin levels throughout life. Children of centenarians show significantly higher circulating humanin than age-matched controls.
Mechanism
Operates via two parallel pathways. Extracellularly: binds a trimeric receptor complex (CNTFR/WSX-1/gp130) activating JAK/STAT3 and ERK1/2 survival cascades; also engages G-protein coupled formylpeptide receptors FPRL1 and FPRL2. Intracellularly: directly sequesters pro-apoptotic proteins BAX, tBID, and BimEL, blocking their translocation to the mitochondrial membrane; also neutralises IGFBP3-induced apoptosis. Additional actions include stimulating chaperone-mediated autophagy (CMA), activating PI3K/AKT (promoting mitochondrial biogenesis in dopaminergic neurons), and upregulating BCL-2. Net result: suppression of apoptosis, necroptosis, and necrosis under oxidative stress, hypoxia, amyloid-beta exposure, and serum starvation.
Outcome
Animal/preclinical findings: reduces Alzheimer's-associated amyloid-beta neuronal toxicity and cognitive decline in transgenic AD mice; cuts myocardial infarct size by ~50% in ischaemia models; improves insulin sensitivity and lowers blood glucose in diabetic rats; extends C. elegans lifespan ~7% (daf-16/FOXO dependent); protects retinal pigment epithelium from oxidative damage; preserves male fertility during chemotherapy. Human correlational data: circulating humanin inversely correlated with Alzheimer's disease, MELAS syndrome, and type 2 diabetes; positively associated with coronary endothelial function and inherited longevity. No completed human interventional clinical trials as of 2026.
