MOTS-c
A 16-amino-acid peptide encoded in mitochondrial DNA that acts as an exercise-mimetic metabolic regulator in mice. Human data is observational only.
Longevity
Humanin
A peptide encoded in mitochondrial DNA rather than the nuclear genome. Levels fall with age and correlate with longevity in humans, but no therapeutic trial exists.
Overview
Humanin was found while researchers were looking for genes that protected brain cells from Alzheimer-related death. It turned out to be encoded not in the cell nucleus but inside the mitochondrial genome, which was unexpected — mitochondria were not thought to produce signalling peptides. It protects cells from several kinds of stress-induced death, and blood levels decline steadily with age. Long-lived people and centenarians' offspring tend to have higher levels.
A 24-amino-acid peptide encoded within the mitochondrial 16S rRNA gene MT-RNR2, the founding member of the mitochondrial-derived peptide family alongside MOTS-c and the SHLPs. Binds a trimeric receptor complex of CNTFR, WSX-1 and gp130 to activate STAT3, and interacts with BAX and IGFBP-3 to inhibit apoptosis. Circulating levels correlate inversely with age and positively with longevity markers in human cohorts. The potent analogue HNG (S14G-humanin) is used in most animal work. Preclinical effects include improved insulin sensitivity, reduced atherosclerosis and neuroprotection. No registered human therapeutic trial has been conducted.
Research areas
Ageing biologyAlzheimer's diseaseInsulin sensitivityMitochondrial signalling
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| Intraperitoneal HNG in rodent models of insulin resistance and neurodegeneration | Muzumdar et al., PLoS One 2009 |
| Observational measurement of circulating humanin across age groups and in centenarian offspringObservational — this establishes correlation with age and longevity, not that supplementation does anything. | Yen et al., Aging 2020 |
Trial status
Human observational studies of endogenous levels exist. No interventional trials.
Reported safety signals
- No human interventional safety data exists.
- Its core mechanism is apoptosis inhibition, which is exactly what cancer cells exploit — an unaddressed concern for chronic administration.
- Sold through unregulated channels with unverified identity.
Common questions
Why does it matter that humanin comes from mitochondrial DNA?
Because it upended the assumption that mitochondria only supply energy and take instructions from the nucleus. Humanin and MOTS-c showed the mitochondrial genome encodes signalling peptides that act on the rest of the body — a genuinely new layer of physiology.
Primary sources
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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