Happy Tuesday!
I just launched a brand new episode on Humanin, and it’s live right now on Spotify and iTunes.
This one is really cool because Humanin is a mitochondrial peptide most people have never heard of.
It’s different from SS-31 and MOTS-c and I predict it is going to matter more and more as brain health becomes the issue of our lifetime.
If you have had someone in your family deal with Alzheimer’s, dementia, or cognitive decline, you already know why I care about this topic.
Humanin is one of the few peptides that keeps showing up in the research as a cell-protective signal tied to aging, stress resilience, and cognition.
Let’s dive into what it does.
FYI, BioLongevity Labs is still offering 40% off all injectable peptides and bioregulators. You can use code HUNTERW at checkout for an extra 15% off.
Background
Humanin is an endogenous mitochondrial-derived peptide, meaning your body naturally produces it.
It’s 24 amino acids and encoded inside mitochondrial DNA, not your nuclear DNA.
Specifically, it’s embedded as a small open reading frame within the mitochondrial 16S rRNA gene.
This matters because mitochondria are not just “energy factories.”
They’re one of the main control centers for aging.
They regulate energy output, oxidative stress, inflammatory signaling, and apoptosis, a programmed form of cell death.
And what Humanin appears to be is one of the “messages” mitochondria release when the cell is under threat.
In multiple species, humanin levels tend to decline with age, and in families with exceptional longevity, circulating levels are higher.
That doesn’t prove supplementation equals longevity, but it does tell us Humanin is correlated with the biology of long life.
Mechanisms
Once Humanin is present in the system, it works on two levels.
First, it binds to cell surface receptors and turns on survival pathways.
Humanin’s biology is tied to signaling like STAT3, and studies have actually measured a 10-fold increase in hypothalamic STAT3 phosphorylation after central Humanin infusion.
Second, Humanin exhibits a “soldier peptide” behavior, blocking cell death at the mitochondrial level.
In one paper, they describe Humanin as cytoprotective across many insults, and in another paper they frame Humanin as neuroprotective both in vitro and in vivo.
In plain English, stress hits the cell, mitochondria start getting damaged, apoptosis pathways get activated, and Humanin is part of the system that says, “No. Not today.”
That’s why I think of it as a stress resilience peptide.
Benefits
Let’s put the benefits into numbers.
Brain and cognitive aging: In a 2018 Scientific Reports paper, they identify a mitochondrial SNP (rs2854128) associated with a 14% decrease in circulating Humanin, and in a large U.S. aging cohort, that SNP was linked to an increase in “cognitive age.”
In African-Americans with the alternate allele, cognitive age was about two years older than those with the reference allele.
This implies that Humanin decline is tied to real-world cognitive aging.
Cardiovascular aging: In old mice treated long-term with the Humanin analog HNG, interstitial collagen deposition (fibrosis) dropped from 0.24% to 0.07%. That’s a massive reduction in the scar-like remodeling that accumulates with age.
They also cut TUNEL-positive apoptosis from 27.8% down to 13.1%.
Humanin supports mitochondrial integrity and cell survival.
Dosage
This is where I’m going to be very direct.
We do not yet have large-scale human supplementation trials for Humanin.
So you’re not going to see an “official” protocol the way you might for other compounds. But we do have a very clear practical framework you can use.
My recommended longevity range: 1 to 2 mg per day, 5 days on, 2 days off for 8-12 weeks.
That schedule keeps it simple, keeps you consistent, and gives you built-in breaks so you don’t run something endlessly for no reason.
Over a week, that’s usually 5 to 10 mg total, depending on whether you’re closer to 1 mg or 2 mg per day.
Most people get Humanin as a 10 mg vial. Here’s what I would do from there:
Reconstitute with 2 mL bacteriostatic water.
If you’re using a standard insulin syringe, 1 mg = 0.2 mL = 20 units.
2 mg = 40 units.
Subcutaneous is the usual route.
If someone is dealing with an actual neurodegenerative situation, that’s a different conversation on dosing. I would probably recommend 5-10mg per day in that case.
But for longevity, stress resilience, and brain aging prevention, the 1-2 mg/day framework is the starting point I like.
Final Thoughts
Humanin is one of the most underutilized peptides in the longevity world right now.
Amongst the mitochondria peptides, in my opinion, it’s the one that leans the hardest into brain health and cell survival.
The data we do have is enough to respect it.
In humans, lower Humanin levels linked to genetics show up as measurable cognitive aging differences, including a reported two-year shift in cognitive age in certain groups.
In aged mice, Humanin analog treatment dramatically reduced markers of fibrosis and apoptosis in the heart.
My take is simple.
You rotate mitochondrial support throughout the year. You stay sensitive. You stay consistent.
And you keep your mitochondria and your brain in the best environment possible.
If you want deeper guidance, check out the Axion Collective.
Taylor and I do live coaching calls every Thursday at 8 pm EST.
Best,
Hunter Williams