Humanin 10 MG

Description

Humanin is a naturally occurring micro-peptide notable for being encoded within mitochondrial DNA—a rare feature, as most proteins are encoded by nuclear DNA. It acts as a cytoprotective agent by interfering with Bcl2-associated X protein (Bax), thereby inhibiting apoptosis, or programmed cell death. Humanin variants have been identified in several mammals, including humans and rats, and are highly conserved across species, suggesting an essential biological function [1]. Studies indicate that Humanin provides protective effects in neurons, cardiac tissue, skeletal muscle, retinal cells, and vascular endothelium.

Humanin Structure

Source: Pubchem

Sequence: Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala Molecular Formula: C119H204N34O32S2
Molecular Weight: 2687.3 g/mol
PubChem SID: 16131438
CAS Number: 330936-69-1
Synonyms: formyl humanin, HNGF6A protein

Humanin Research

What Are Micro-peptides and How Does Humanin Protect the Brain?

Unlike traditional peptides and proteins, which are derived from post-translational modification of larger precursors, micro-peptides are translated directly from short open reading frames (sORFs) and typically bypass post-translational modification. Ranging from 100 to 150 amino acids in length, these sORFs were long overlooked by scientists, who once assumed that all functional peptides followed the full DNA → RNA → protein → modified protein pathway. The discovery of micro-peptides challenged that assumption, revealing that some peptides are functional immediately upon translation.

In humans, multiple sORFs have been identified, with functions that include enhancing mRNA processing, repairing DNA damage, and interacting with larger proteins to form complex assemblies. Humanin, one of the smallest micro-peptides identified to date, is just 24 amino acids long. It plays a key role in regulating apoptosis by interacting with Bcl2-associated X protein (Bax), blocking its function to preserve cells that might otherwise undergo programmed death.

Neuroprotection

Animal studies demonstrate that humanin not only inhibits apoptosis in general but also offers targeted neuroprotection. For example, in rat models of Alzheimer’s disease, humanin prevents neuron death caused by beta-amyloid accumulation [3]. Additional experiments show that it guards against excitotoxicity in neurons exposed to NMDA stimulation [1].

Similar protective effects have been observed in models of prion disease [4]. While humanin may not address the root causes of neurodegenerative conditions—such as plaque formation in Alzheimer’s—it may help slow disease progression by tipping the physiologic balance away from excessive apoptosis [5].

Humanin appears to block apoptosis via two mechanisms, both centered on preventing mitochondrial activation of cell death pathways. Under normal conditions, Bcl-2 family proteins signal mitochondria to release factors that activate caspases, the enzymes that coordinate cell breakdown and recycling [6]. Though this is beneficial in some cases (e.g., to prevent viral spread), it can lead to uncontrolled cell death in chronic disease. Humanin interferes with Bid and tBid—proteins that stimulate Bcl-2—and halts the apoptotic cascade at its source [7].

Emerging research from Argentina shows that humanin is secreted by astrocytes to protect synapses in hippocampal neurons [8]. This supports the hypothesis that declining humanin levels may contribute to age-related memory loss and increased risk of neurodegeneration. Some scientists now speculate that humanin supplementation could become a novel approach to mitigating cognitive decline in aging populations.

Humanin levels in relation to age. A significant decline in humanin levels is seen in older individuals.
Source: PubMed

Humanin Interfaces with IGF-1

Recent research from the University of Southern California has demonstrated that humanin interacts with insulin-like growth factor 1 (IGF-1). Specifically, humanin reduces circulating IGF-1 levels, while IGF-1 modulates humanin levels in return. Although the precise mechanisms of this interaction remain unclear, current evidence strongly suggests that humanin plays a significant role in IGF-1 signaling. These peptides exhibit both synergistic and antagonistic effects: they jointly inhibit apoptosis, enhance insulin sensitivity, reduce inflammation, and offer protection against certain cardiovascular diseases. In other contexts, they oppose each other’s effects. Further research is needed to clarify the pathways involved, but their mutual influence is well established [9].

Heart Disease

Research from the Mayo Clinic indicates that humanin is expressed in the walls of human blood vessels, where it provides protection against damage caused by oxidized low-density lipoprotein (LDL) cholesterol. Humanin reduces the formation of reactive oxygen species (ROS) triggered by LDL oxidation, resulting in a 50% reduction in both ROS levels and apoptosis in vascular tissues [10].

Although it is known that humanin levels decline with age, recent findings suggest that various disease states may also influence its expression. In the field of cardiology, researchers have long sought reliable biomarkers of mitochondrial function, especially in the context of cardiovascular disease. Since mitochondrial health reflects ischemia and disease progression, humanin may serve as a valuable diagnostic marker. Russian studies have found that humanin levels decline proportionally with cardiovascular disease severity [11]. This positions humanin as both a potential diagnostic tool and a therapeutic agent, as supplementation may help support compromised mitochondria.

Humanin Research and Retinal Disease

The retinal pigment epithelium (RPE) is a critical layer of the retina involved in nourishing retinal cells, filtering blood components, scattering light, and maintaining immune privilege within the eye. Damage to the RPE is commonly observed in age-related macular degeneration, diabetic retinopathy, and other major eye diseases. Current research shows that humanin plays a protective role in the RPE by reducing oxidative stress. In cell culture studies, humanin supplementation improves RPE function and increases resistance to apoptosis [12]. These findings may contribute to the development of new therapeutic and preventive strategies for retinal conditions such as macular degeneration.

Bone Health

Bone loss is a prevalent issue, particularly among aging women and individuals with certain medical conditions or treatments. Glucocorticoids—commonly used to treat autoimmune inflammation—are notorious for causing significant bone loss when administered in high doses or over extended periods. Research from Sweden and Korea has identified two protective effects of humanin on bone health. First, humanin prevents the death of chondrocytes—the cells that produce the collagen framework essential for bone development—without interfering with the anti-inflammatory effects of drugs like dexamethasone [13]. This action promotes cartilage and bone growth, counteracting glucocorticoid-induced bone loss.

Additionally, humanin appears to suppress osteoclast formation. Osteoclasts are essential for normal bone remodeling but can cause excessive bone degradation when overactive. By limiting osteoclast development, humanin helps prevent abnormal bone loss [14].

Notes on Use and Availability

In animal studies, humanin demonstrates low side effects, good oral bioavailability, and excellent subcutaneous absorption. However, dosing in mice does not translate directly to human use. Humanin sold by Peptide Sciences is intended solely for educational and scientific research purposes and is not approved for human consumption. It should only be purchased and used by licensed researchers.

Article Author

The above literature was researched, edited, and organized by Dr. Logan, M.D. Dr. Logan holds a Doctor of Medicine degree from Case Western Reserve University School of Medicine and a Bachelor of Science in Molecular Biology.

Scientific Journal Authors

Dr. Pinchas Cohen, M.D., is the Dean of the USC Leonard Davis School of Gerontology, Executive Director of the Ethel Percy Andrus Gerontology Center, and holder of the William and Sylvia Kugel Dean’s Chair in Gerontology. A pioneering researcher in mitochondrial peptides, Dr. Cohen is recognized for discovering several such peptides, including humanin, a 24-amino acid peptide encoded by the mt-16S-rRNA. His research focuses on the therapeutic potential of these peptides in conditions such as diabetes, Alzheimer’s disease, and age-related disorders. Other mitochondrial peptides under his investigation include:

• MOTS-c, encoded in the 12S region of the mitochondrial genome, which shows anti-diabetic and anti-obesity effects and acts as an exercise mimetic.
• SHLP2, encoded from the light strand of the mt-16S-rRNA, whose expression levels have been correlated with prostate cancer.

Dr. Alfonso Eirin, M.D., earned his medical degree in 2004 from the University of the Republic in Montevideo, Uruguay. He currently serves as a Senior Research Fellow in the Division of Nephrology and Hypertension at the Mayo Clinic in Rochester, Minnesota. Dr. Eirin’s research is centered on the mechanisms of renal and cardiac injury in atherosclerotic renovascular disease (ARVD) and the development of treatment strategies to improve renal outcomes and blood pressure regulation following revascularization.

Important Disclaimer

Dr. Pinchas Cohen (referenced in [9]) and Dr. Alfonso Eirin (referenced in [10]) are cited as leading scientists whose research has significantly advanced the understanding of humanin. These citations are solely for the purpose of acknowledging their scientific contributions. Neither Dr. Cohen nor Dr. Eirin is affiliated with, endorses, or advocates for the sale, purchase, or use of humanin or any product containing it. There is no implied or explicit relationship between these researchers and Peptide Sciences.

References

1. A. Caricasole, V. Bruno, I. Cappuccio, D. Melchiorri, A. Copani, and F. Nicoletti, “A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity,” FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., vol. 16, no. 10, pp. 1331–1333, Aug. 2002.
2. PubChem, “Humanin.” [Online]. Available: https://pubchem.ncbi.nlm.nih.gov/compound/16131438. [Accessed: 11-Sep-2019].
3. M. Matsuoka, “Humanin; a defender against Alzheimer’s disease?,” Recent Patents CNS Drug Discov., vol. 4, no. 1, pp. 37–42, Jan. 2009.
4. I. Sponne, A. Fifre, V. Koziel, B. Kriem, T. Oster, and T. Pillot, “Humanin rescues cortical neurons from prion-peptide-induced apoptosis,” Mol. Cell. Neurosci., vol. 25, no. 1, pp. 95–102, Jan. 2004.
5. A. R. White et al., “Sublethal concentrations of prion peptide PrP106-126 or the amyloid beta peptide of Alzheimer’s disease activates expression of proapoptotic markers in primary cortical neurons,” Neurobiol. Dis., vol. 8, no. 2, pp. 299–316, Apr. 2001.
6. C. Wang and R. J. Youle, “The Role of Mitochondria in Apoptosis,” Annu. Rev. Genet., vol. 43, pp. 95–118, 2009.
7. D. Zhai, F. Luciano, X. Zhu, B. Guo, A. C. Satterthwait, and J. C. Reed, “Humanin binds and nullifies Bid activity by blocking its activation of Bax and Bak,” J. Biol. Chem., vol. 280, no. 16, pp. 15815–15824, Apr. 2005.
8. S. C. Zárate, M. E. Traetta, M. G. Codagnone, A. Seilicovich, and A. G. Reinés, “Humanin, a Mitochondrial-Derived Peptide Released by Astrocytes, Prevents Synapse Loss in Hippocampal Neurons,” Front. Aging Neurosci., vol. 11, p. 123, 2019. 
9. J. Xiao, S.-J. Kim, P. Cohen, and K. Yen, “Humanin: Functional Interfaces with IGF-I,” Growth Horm. IGF Res. Off. J. Growth Horm. Res. Soc. Int. IGF Res. Soc., vol. 29, pp. 21–27, 2016.
10. A. R. Bachar et al., “Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress,” Cardiovasc. Res., vol. 88, no. 2, pp. 360–366, Nov. 2010.
11. A. A. Zhloba, T. F. Subbotina, N. S. Molchan, and Y. S. Polushin, “[The level of circulating humanin in patients with ischemic heart disease.],” Klin. Lab. Diagn., vol. 63, no. 8, pp. 466–470, 2018.
12. Sreekumar, Parameswaran & Ishikawa, Keijiro & Spee, Chris & Mehta, Hemal & Wan, Junxiang & Yen, Kelvin & Kannan, Ram & Hinton, David. (2016). The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction. Investigative Opthalmology & Visual Science. 57. 1238. 10.1167/iovs.15-17053. 
13. B. Celvin, F. Zaman, C. Aulin, and L. Sävendahl, “Humanin prevents undesired apoptosis of chondrocytes without interfering with the anti-inflammatory effect of dexamethasone in collagen-induced arthritis,” Clin. Exp. Rheumatol., Jun. 2019.
14. N. Kang, K. W. Kim, and D. M. Shin, “Humanin suppresses receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via AMP-activated protein kinase activation,” Korean J. Physiol. Pharmacol. Off. J. Korean Physiol. Soc. Korean Soc. Pharmacol., vol. 23, no. 5, pp. 411–417, Sep. 2019.

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