Humanin is a small peptide, 24 amino acids long, encoded in the DNA of mitochondria, the energy-producing parts of cells.[3][11] Japanese researchers discovered it in 2001 because it protected nerve cells from damage caused by Alzheimer’s disease genes.[1] It has never been tested as a treatment in a human trial, and it is not an approved medicine.[16][17]
What is humanin?
Humanin was found by screening genes from an apparently normal region of a brain affected by Alzheimer’s disease.[3] The gene sits in the mitochondrial 16S ribosomal RNA gene (MT-RNR2).[11] It was the first of a family now called mitochondrial-derived peptides, which also includes MOTS-c and six small humanin-like peptides (SHLPs).[12][13]
The best-known lab version is HNG (also called S14G-humanin or humanin-G), in which one amino acid is swapped. In early cell studies, HNG blocked all five Alzheimer’s-related insults tested, while three other growth factors blocked only some of them.[2]
How humanin works
Most of what is known comes from cell and animal studies:
- Cell-surface receptors: humanin acts on FPRL1, a receptor also used by amyloid-beta, which may let it block amyloid’s effects.[3] It also binds a three-part receptor complex (CNTFR, WSX-1 and gp130) that switches on protective STAT3 signaling.[4]
- IGFBP-3: it binds this growth-factor-binding protein, and the pair can work together or against each other depending on the cell type. In nerve cells, IGFBP-3 strengthened humanin’s protection against amyloid-beta.[5]
- Insulin: in rodents, humanin delivered to the brain improved insulin sensitivity through the hypothalamus, and a potent analog lowered blood sugar in diabetic rats.[6]
- Energy: in muscle cells, humanin may raise ATP, the cell’s energy currency.[14]
Humanin benefits: what the research shows
Brain and Alzheimer’s disease
- Cells: humanin blocked nerve cell death caused by several familial Alzheimer’s genes and by amyloid-beta, but not by unrelated toxins such as glutamate.[1][2]
- Mice: humanin improved cognition in aged mice.[7]
- People: a variant in the humanin gene that lowers blood humanin was linked to faster cognitive aging in a large, nationally representative group of older adults.[7] People with Alzheimer’s disease had lower humanin levels than healthy controls in two studies.[8][9]
Aging and lifespan
- Worms: adding extra humanin lengthened lifespan in C. elegans.[8]
- Mice: twice-weekly HNG injections in middle-aged mice improved metabolic health markers and reduced inflammation markers.[8]
- Naked mole-rats: humanin levels stayed unusually stable with age in this long-lived rodent.[8]
Human association studies
These studies measure the body’s own humanin. They show links, not cause and effect:
- Age: blood humanin was lower in older people and mice in a US study,[6] but an Italian study of healthy adults found levels rose with age.[9]
- Centenarians’ offspring: children of people who lived to 100 had much higher blood humanin than people of the same age.[8]
- Heart: people with poor coronary artery function had lower humanin (1.3 vs 2.2 ng/mL) than those with normal function.[10] A Russian study found lower humanin in 59 people with coronary heart disease than in healthy people.[15]
- Exercise: one session of hard interval cycling raised humanin in the muscle and blood of 10 young men.[11]
- Mitochondrial disease: humanin was increased in damaged muscle fibers from people with MELAS, a mitochondrial disorder.[14]
Small humanin-like peptides (SHLPs)
The same stretch of mitochondrial DNA that encodes humanin holds six more short peptides, named small humanin-like peptides 1 to 6. In cell studies, SHLP2 and SHLP3 behaved much like humanin: they reduced cell death and harmful reactive oxygen species and improved mitochondrial metabolism. In rodents, SHLP2 delivered to the brain improved insulin sensitivity, and like humanin, its blood levels fell with age.[12] In young men, a hard cycling session raised blood SHLP6 along with humanin, but not SHLP2.[11] None of these peptides has been tested as a treatment in people.
Humanin dosage
There is no established human dose. We found no registered trial that has given humanin to people,[17] and doses used in animal studies do not tell us what is safe or effective in humans. New Zealand’s regulator reported that mitochondria-derived peptides are imported for personal use and marketed for lifespan, inflammation and metabolism, while their protective effects have not been shown in humans.[16]
Humanin side effects and safety
Humanin’s side effects in people are unknown because it has not been given to people in published trials.[17] General risks of unregulated injectable peptides include impurities, contamination and immune reactions. Because humanin acts on growth and cell-survival pathways, including IGFBP-3,[5] long-term effects in people cannot be predicted from cell and animal work.
Humanin vs MOTS-c
| Humanin | MOTS-c | |
|---|---|---|
| Discovered | 2001, Japan[1] | 2015, USC[13] |
| Gene location | Mitochondrial 16S rRNA[11] | Mitochondrial 12S rRNA[13] |
| Length | 24 amino acids[3] | 16 amino acids[13] |
| First studied for | Brain cell protection[1] | Insulin sensitivity and metabolism[13] |
| Human treatment trials | None[17] | Only an analog (CB4211)[19] |
The MOTS-c discoverers said humanin’s existence prompted them to look for other peptides hidden in mitochondrial DNA.[13] New Zealand’s regulator grouped both under one proposed prescription-only class after people imported them for personal use.[16]
Humanin vs SS-31
SS-31 (elamipretide) is often mentioned alongside humanin, but it is different. It is a synthetic peptide designed to act on mitochondria, not made by them, and in 2025 it received FDA accelerated approval as Forzinity to improve muscle strength in Barth syndrome.[18] Humanin has no approval for any condition.
Is humanin legal?
- US: humanin is not an FDA-approved drug, and we found no registered human treatment trial.[17]
- New Zealand: in 2025, Medsafe proposed classifying humanin, MOTS-c and other mitochondria-derived peptides as prescription medicines after people imported them for personal use. It said none of them were scheduled in New Zealand or Australia at the time.[16]
This is general information, not legal advice. For other peptides marketed for aging, see our longevity peptides overview, and for brain-focused peptides, our cognitive peptides overview.
