Humanin
A 24-amino-acid peptide naturally produced by mitochondria. Related to MOTS-c but works differently. Protects cells against oxidative stress, cell death, and age-related damage by interacting with proteins involved in apoptosis and IGF signaling. One of the most studied peptides in longevity research, with evidence that levels decline in aging tissues.
Dosage
1-5 mg subcutaneous daily (research, HNG analogue)
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Administration
Subcutaneous injection (research)
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Effects
Cytoprotection
Blocks BAX-mediated apoptosis and protects cells from oxidative stress.
Anti-Aging
Levels decline 40% with age — restoration addresses cellular vulnerability.
Insulin Sensitivity
Improves glucose handling through STAT3-mediated signaling.
Mechanism of Action
Humanin is a 24-amino-acid peptide (MAPRGFSCLLLLTSEIDLPVKRRA) encoded within the 16S ribosomal RNA gene of the mitochondrial genome. Its discovery in 2001 was revolutionary — it was the first identified mitochondrial-derived peptide (MDP), challenging the long-held dogma that the mitochondrial genome only encodes 13 oxidative phosphorylation subunits, 22 tRNAs, and 2 rRNAs. Humanin, along with MOTS-C and the SHLP peptides discovered later, established mitochondria as endocrine organelles.
Humanin exerts cytoprotective effects through multiple mechanisms. Extracellularly, it binds to a trimeric receptor complex composed of CNTFR (ciliary neurotrophic factor receptor alpha), WSX-1 (IL-27 receptor alpha), and gp130 (the shared signaling subunit of the IL-6 receptor family). Activation of this complex triggers JAK/STAT3 signaling, which drives expression of anti-apoptotic genes (Bcl-2, Mcl-1) and cell survival programs. Intracellularly, humanin interacts directly with two pro-apoptotic proteins: it binds IGFBP-3, preventing IGFBP-3 from translocating to mitochondria and initiating apoptosis; and it binds BAX (Bcl-2-associated X protein), preventing BAX oligomerization and insertion into the outer mitochondrial membrane — the critical step in the intrinsic (mitochondrial) apoptosis pathway that releases cytochrome c and activates caspases.
Humanin also reduces cellular stress through multiple pathways. It decreases reactive oxygen species (ROS) production by optimizing mitochondrial electron transport chain function. It reduces endoplasmic reticulum (ER) stress by modulating the unfolded protein response (UPR). It improves insulin sensitivity through STAT3-mediated effects on hypothalamic signaling and peripheral insulin receptor substrate phosphorylation. Circulating humanin levels decline with age (approximately 40% reduction between youth and old age) and are inversely correlated with markers of age-related disease, suggesting that humanin decline contributes to the increased cellular vulnerability and apoptosis susceptibility seen in aging. Its most potent synthetic analogue, HNG (S14G-humanin), has a glycine-for-serine substitution at position 14 that increases cytoprotective potency approximately 1,000-fold.
Regulatory Status
Not FDA approved. Active area of research at major institutions (USC, Albert Einstein College of Medicine). Humanin analogues (HNG, S14G-Humanin) used in preclinical studies. Available through research suppliers.
Risks & Safety
Common
injection site irritation, mild fatigue.
Serious
limited human safety data, may protect cancer cells from programmed death (BAX interaction), may affect IGF-1 signaling.
Rare
allergic reactions.
Compare Humanin With
Research Papers
30Published: February 2, 2026
AI Summary
Adding humanin to bull semen at 5 micromolar improved post-thaw quality, antioxidant status, and in vitro fertility. The peptide may enhance sperm freezability for breeding programs.
Published: March 5, 2026
AI Summary
Humanin prevented steroid-induced bone growth problems and bone loss in Duchenne muscular dystrophy mice. The peptide may improve bone health during glucocorticoid therapy without worsening muscle.
Published: January 31, 2026
AI Summary
A review summarizes how mitochondria-derived peptides like humanin regulate liver metabolism and protect against fatty liver disease. Humanin inhibits cell death and modulates lipid metabolism.
Published: January 9, 2026
AI Summary
Researchers evaluated serum humanin as a possible breast cancer biomarker in Egyptian women. The abstract notes humanin's cytoprotective role; full results would show diagnostic performance.
Published: December 14, 2025
AI Summary
A review covers mitochondrial DNA's roles in colorectal cancer, including humanin's dual tumor-promoting and cytoprotective effects. mtDNA may inform liquid biopsies and treatment.
Published: November 28, 2025
AI Summary
SHLP2 protected bone-forming cells from oxidative stress, reduced cell death, and restored bone mineralization. The peptide may help in periodontitis and age-related bone loss.
Published: November 8, 2025
AI Summary
Blood and plasma humanin and MOTS-c RNA levels were lower in Alzheimer's patients than in controls; protein levels did not distinguish groups. Transcript levels may serve as early AD biomarkers.
Published: October 28, 2025
AI Summary
Herkinorin protected human neurons from oxygen-glucose deprivation by affecting opioid receptor trafficking. The abstract describes the model; full results would clarify neuroprotection mechanisms.
Published: November 3, 2025
AI Summary
Abstract too short to summarize.
Published: October 13, 2025
AI Summary
Researchers examined nitrosative stress, humanin, MOTS-c, and ferroptosis in corneal cells from keratoconus patients. The abstract states the aim; full findings would clarify their roles.
Published: October 8, 2025
AI Summary
Machine learning linked humanin and other mitochondrial markers to heart disease risk in early diabetes stages. Biomarker importance shifted from mitochondrial to inflammatory markers as diabetes progressed.
Published: September 26, 2025
AI Summary
Exercise improved heart function in aging rats by raising humanin and IGF-1 levels. Both moderate and high-intensity training may benefit the heart through the IGF-1-humanin pathway.
Published: October 6, 2025
AI Summary
Computer modeling and zebrafish tests suggested SHLP6 may protect against neurodegeneration and aging by modulating apoptosis and antioxidant pathways. The peptide reduced stress-induced damage.
Published: August 27, 2025
AI Summary
Humanin produced by macrophages that clear dead cells helped resolve inflammation in mice and dampened inflammatory cytokine release from human neutrophils. The peptide may aid inflammation resolution.
Published: August 28, 2025
AI Summary
Humanin was detected in goat testes, epididymis, and sperm, with stronger expression in the rainy season when sperm quality was higher. The peptide may support male reproductive function.
Published: August 5, 2025
AI Summary
Humanin and GAS5 were lower in prostate cancer than in benign disease; combining them with MOTS-c and miRNAs improved risk stratification. The panel may aid non-invasive prostate cancer diagnosis.
Published: December 25, 2025
AI Summary
A review evaluates humanin, MOTS-c, and SHLPs as potential treatments for Alzheimer's, Parkinson's, and Huntington's. The peptides may reduce oxidative stress and neuroinflammation; clinical translation needs more work.
Published: September 16, 2025
AI Summary
A review covers mitochondrial-derived peptides in Parkinson's disease. Humanin, SHLPs, and MOTS-c may modulate stress, inflammation, and metabolism, offering new therapeutic targets.
Published: September 6, 2025
AI Summary
Researchers tested whether Gly[14]-humanin improves cyclophosphamide-induced premature ovarian failure. The abstract states the aim; full results would show whether the peptide protects ovarian function.
Published: June 19, 2025
AI Summary
A review covers how humanin, MOTS-c, and SHLPs may protect blood vessels from aging and cardiovascular disease. The peptides regulate apoptosis, inflammation, and oxidative stress in vascular cells.
Published: July 18, 2025
AI Summary
Humanin can form amyloid-like fibrils; certain mutants that block fibrillization also impair secretion and BCL-2 binding. The work clarifies humanin's structure and how it inhibits cell death.
Published: March 31, 2025
AI Summary
SHLP-6 protected zebrafish from copper-induced oxidative stress and neurodegeneration by modulating NLRP3 and Cav1. The peptide may help in copper toxicity and related brain injury.
Published: July 4, 2025
AI Summary
A review discusses humanin's role in Alzheimer's: it protects neurons from amyloid toxicity and oxidative stress, but aging and AD studies show conflicting levels. The work clarifies possible mechanisms.
Published: May 13, 2025
AI Summary
A review summarizes how humanin and MOTS-c may protect the heart and blood vessels. The peptides improve mitochondrial function and reduce oxidative damage; delivery and stability remain challenges.
Published: February 16, 2025
AI Summary
MOTS-c protected retinal cells from hypoxia and regulated genes involved in apoptosis and mitochondrial biogenesis. The peptide may help in age-related macular degeneration; effects differed by cell type.
Published: October 21, 2025
AI Summary
A review examines humanin's role in autophagy. The peptide and its analog HNG may induce autophagy and promote cell survival under metabolic and oxidative stress.
Published: February 13, 2025
AI Summary
High-intensity interval training raised serum humanin and reduced inflammation and oxidative stress in diabetic rats. Humanin may partly explain exercise's benefits in type 2 diabetes.
Published: January 20, 2025
AI Summary
Humanin reduced iron-dependent cell death in disc cells and slowed disc degeneration in lab and animal models. The peptide may offer a new way to treat low back pain from disc disease.
Published: January 13, 2025
AI Summary
Higher humanin levels were linked to better blood vessel function and survival in rheumatoid arthritis patients. The peptide may be a protective biomarker for cardiovascular risk in RA.
Published: February 4, 2025
AI Summary
Mismatched early nutrition reduced humanin in pancreatic beta cells and impaired insulin release; restoring humanin and FGF21 may reverse the damage. The work links perinatal diet to later diabetes risk.
Frequently Asked Questions
What is Humanin?
A 24-amino-acid peptide naturally produced by mitochondria. Related to MOTS-c but works differently. Protects cells against oxidative stress, cell death, and age-related damage by interacting with proteins involved in apoptosis and IGF signaling. One of the most studied peptides in longevity research, with evidence that levels decline in aging tissues.
What is Humanin used for?
A 24-amino-acid peptide naturally produced by mitochondria. Related to MOTS-c but works differently. Protects cells against oxidative stress, cell death, and age-related damage by interacting with proteins involved in apoptosis and IGF signaling. One of the most studied peptides in longevity research, with evidence that levels decline in aging tissues.
What is the dosage for Humanin?
No established clinical dosing. Research analogue (HNG — humanin G): most commonly used form. User-reported: 1-5 mg subcutaneous once daily. Often cycled 4-8 weeks.
What are the side effects of Humanin?
Common: injection site irritation, mild fatigue. Serious: limited human safety data, may protect cancer cells from programmed death (BAX interaction), may affect IGF-1 signaling. Rare: allergic reactions.
How does Humanin work?
Humanin is a 24-amino-acid peptide (MAPRGFSCLLLLTSEIDLPVKRRA) encoded within the 16S ribosomal RNA gene of the mitochondrial genome. Its discovery in 2001 was revolutionary — it was the first identified mitochondrial-derived peptide (MDP), challenging the long-held dogma that the mitochondrial genome only encodes 13 oxidative phosphorylation subunits, 22 tRNAs, and 2 rRNAs. Humanin, along with MOTS-C and the SHLP peptides discovered later, established mitochondria as endocrine organelles. Humanin exerts cytoprotective effects through multiple mechanisms. Extracellularly, it binds to a trimeric receptor complex composed of CNTFR (ciliary neurotrophic factor receptor alpha), WSX-1 (IL-27 receptor alpha), and gp130 (the shared signaling subunit of the IL-6 receptor family). Activation of this complex triggers JAK/STAT3 signaling, which drives expression of anti-apoptotic genes (Bcl-2, Mcl-1) and cell survival programs. Intracellularly, humanin interacts directly with two pro-apoptotic proteins: it binds IGFBP-3, preventing IGFBP-3 from translocating to mitochondria and initiating apoptosis; and it binds BAX (Bcl-2-associated X protein), preventing BAX oligomerization and insertion into the outer mitochondrial membrane — the critical step in the intrinsic (mitochondrial) apoptosis pathway that releases cytochrome c and activates caspases. Humanin also reduces cellular stress through multiple pathways. It decreases reactive oxygen species (ROS) production by optimizing mitochondrial electron transport chain function. It reduces endoplasmic reticulum (ER) stress by modulating the unfolded protein response (UPR). It improves insulin sensitivity through STAT3-mediated effects on hypothalamic signaling and peripheral insulin receptor substrate phosphorylation. Circulating humanin levels decline with age (approximately 40% reduction between youth and old age) and are inversely correlated with markers of age-related disease, suggesting that humanin decline contributes to the increased cellular vulnerability and apoptosis susceptibility seen in aging. Its most potent synthetic analogue, HNG (S14G-humanin), has a glycine-for-serine substitution at position 14 that increases cytoprotective potency approximately 1,000-fold.
How is Humanin administered?
Humanin is administered via subcutaneous injection (research).
What is the half-life of Humanin?
The half-life of Humanin is 0.5-4 hours (varies by analogue; HNG has extended activity).
Is Humanin legal?
Not FDA approved. Active area of research at major institutions (USC, Albert Einstein College of Medicine). Humanin analogues (HNG, S14G-Humanin) used in preclinical studies. Available through research suppliers.
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