Humanin

Discovered in 2001 because it protected nerve cells from Alzheimer's-linked damage in the lab. It is encoded in mitochondrial DNA (the MT-RNR2 gene). Blood levels fall with age and are higher in the children of centenarians.

Outside cells it binds receptors that switch on survival signaling (JAK2/STAT3, PI3K/AKT, ERK). Inside cells it binds the cell-death proteins Bax and tBid and keeps them away from mitochondria. It also binds IGFBP-3, linking it to the IGF-1 system.

Human studies are observational: levels drop with age, are higher in centenarians' offspring, are lower in Alzheimer's spinal fluid and type 2 diabetes, and rise with exercise. In mice, the more potent analog HNG improved memory in Alzheimer's models, delayed ALS onset, reduced stroke and heart-attack damage, and reduced visceral fat in aged mice without extending lifespan. Overexpression modestly extended lifespan in worms. Human pharmacokinetics, brain uptake and cancer risk are unknown, and whether higher levels cause better aging or simply mark it is unclear.

No human side-effect data exists because it has never been given to people in a trial. The main theoretical concern is cancer: humanin is elevated in some gastric and bladder tumors, and some lab work shows it promoting tumor progression, though other work shows it shielding normal cells from chemotherapy. Effects on cell aging are mixed.

Not FDA-approved and no human program found. It is not on FDA's 503A nomination or Category 2 lists and has no USP monograph, so it has no lawful compounding pathway. Not named on the WADA list but likely falls under S0 (non-approved substances). Status as of October 2026.