Humanin

Mitochondrial-derived peptide · Also known as HN, HNG (S14G analog), Humanin-G

What is humanin?

A 24-amino-acid peptide encoded within the mitochondrial genome, first discovered in 2001 from brain tissue of Alzheimer's patients. It functions as a stress-response signal from mitochondria, protecting cells from oxidative damage, apoptosis, and metabolic dysfunction.

Humanin was the first identified member of a new class of mitochondrial-derived peptides (MDPs). Research has found that circulating humanin levels decline with age in humans, while centenarians and their children maintain significantly higher levels than age-matched controls. Its potent analog HNG (S14G-humanin) is commonly used in research for enhanced activity.

Key takeaway: Humanin is a naturally occurring mitochondrial peptide linked to longevity and stress resistance, with strong preclinical evidence for neuroprotection and metabolic health, but no completed human clinical trials.

Benefits & evidence

Cellular stress protection Moderate confidence
Neuroprotection Moderate confidence
Metabolic health Preliminary confidence
Anti-aging / longevity Preliminary confidence
Cardiovascular protection Preliminary confidence

How it works

Humanin acts through both intracellular and extracellular pathways. Inside the cell, it binds pro-apoptotic proteins BAX, Bim, and tBid, directly blocking the cascade that triggers programmed cell death. As a secreted peptide, it activates the trimeric CNTFR/gp130/WSX-1 receptor complex, triggering JAK2/STAT3 signaling that promotes cell survival and reduces inflammation.

Humanin also interacts with the FPRL1 receptor to modulate stress-response kinase pathways (ASK1 and JNK). In metabolic contexts, it improves insulin sensitivity and lipid utilization. Animal studies show that biweekly HNG treatment in middle-aged mice reduced visceral fat, increased lean body mass, and lowered inflammatory markers. These effects position humanin as part of mitohormesis, the process where mitochondrial stress signals trigger protective adaptations throughout the body.

Dosing information

Typical dosing protocol
Starting dose

No established human dose

N/A
Maintenance dose

No established human dose

N/A

No completed human clinical trials. Animal studies used HNG analog at doses ranging from 84-252 mcg/kg IV (rat cardiac studies) to 4 mg/kg IP biweekly (mouse aging studies). Some practitioner protocols suggest 5-10 mg/week subcutaneously, but these lack clinical trial validation.

Side effects

Most side effects tend to improve as your body adjusts.

Limited safety data in humans Unknown
Injection site reaction (reported anecdotally) Common

Research (10 studies)