Humanin

The mitochondria, famously known as the “powerhouse of the cell,” does much more than just produce energy. Its dysregulation has been linked to numerous conditions, including cancer, neurodegenerative diseases, cardiovascular disorders, diabetes, brain injury, and inflammation. One of the ways mitochondria help maintain optimal body function is through peptide production.

Introduction to Humanin

Humanin, a mitochondrial-derived peptide, has garnered attention for its potential role in disease prevention and cellular function. Discovered in 2001, Humanin is a 24-amino acid peptide found in various tissues, such as the heart, brain, skeletal muscles, and kidneys. Humanin was initially identified for its protective properties in Alzheimer’s disease, where it demonstrated the ability to prevent neuronal cell death. Since then, research has revealed its broader roles in cellular defense, stress response, and longevity.

How Humanin Works

1. Protection Against Apoptosis (Cell Death): Humanin counters cell death induced by the Bax protein, a key player in apoptosis. By preventing Bax from moving to the mitochondria, Humanin reduces the release of proteins that trigger cell death.
   
   
2. Inflammation and Cellular Stress: Humanin activates signaling pathways, such as JAK/STAT, to protect various cell types, including neurons, leukocytes, and germ cells, under stressful conditions.
   
   
3. Neuroprotective Role: Humanin protects brain cells from toxicity associated with Alzheimer’s disease by interacting with a cytokine-receptor complex, which triggers protective signaling cascades. Its ability to combat amyloid β (Aβ) toxicity has implications for neurodegenerative diseases.
   
   
4. Support for Mitochondrial Health: Humanin enhances mitochondrial metabolism, lowers oxidative stress, and promotes mitochondrial biogenesis. Physical exercise has been shown to naturally boost Humanin production, aiding in glucose tolerance, insulin action, and cellular protection.

Benefits of Humanin

1. Chemotherapy Side Effects: Humanin helps mitigate the toxic effects of chemotherapy drugs, protecting germ cells, neurons, and other tissues from treatment-induced stress and damage.
   
   
2. Cardiovascular Health: Studies suggest a link between Humanin and heart health. Lower Humanin levels correlate with adverse cardiac outcomes, while increased levels provide protection against myocardial injury and oxidative stress in heart tissue.
   
   
3. Potential for Longevity: Research indicates that Humanin levels correlate with longevity. Centenarians tend to have higher Humanin levels, and the peptide has been associated with slower cognitive aging and increased lifespan in animal models.
   
   
4. Alzheimer’s Disease: Humanin’s neuroprotective properties may be beneficial in preventing and treating Alzheimer’s. By inhibiting neuronal cell death, Humanin offers a potential avenue for addressing cognitive decline and dementia.
   
   
5. Diabetes Management: Humanin improves insulin sensitivity and regulates blood glucose levels in diabetic animal models. Lower Humanin levels have been associated with type 2 diabetes, indicating its importance in maintaining metabolic homeostasis.

Additional Potential Benefits

Research on Humanin is still in early stages, but emerging studies suggest other health benefits:

• Anti-inflammatory Effects: Particularly noted in the lungs, suggesting potential applications in respiratory health.
  
  
• Bone and Cartilage Health: A patent exists for Humanin’s protective effects on bone and cartilage, especially against drug-related damage.
  
  
• Hair Growth: Humanin analogs may promote hair growth.
  
  
• Anti-aging Properties: Humanin may inhibit cellular aging mechanisms, potentially playing a role in managing conditions like age-related macular degeneration and chronic fatigue syndrome. 

Conclusion

With over 300 studies conducted since its discovery, Humanin represents a promising therapeutic peptide with diverse health applications. It is increasingly clear that Humanin contributes to more than mitochondrial energy production—it may be key to managing diseases associated with aging, neurodegeneration, and metabolic dysfunction. As research continues, Humanin could become a central figure in age-related and cellular health therapies.

Research

Yen K, Mehta HH, Kim SJ, Lue Y, Hoang J, Guerrero N, Port J, Bi Q, Navarrete G, Brandhorst S, Lewis KN, Wan J, Swerdloff R, Mattison JA, Buffenstein R, Breton CV, Wang C, Longo V, Atzmon G, Wallace D, Barzilai N, Cohen P. The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan. Aging (Albany NY). 2020 Jun 23;12(12):11185-11199. doi: 10.18632/aging.103534. Epub 2020 Jun 23. PMID: 32575074; PMCID: PMC7343442.

Aviv Cohen, Jenny Lerner-Yardeni, David Meridor, Roni Kasher, Ilana Nathan, Abraham H Parola. Humanin: A Multifactorial Anti-death Agent. Biochemistry and Molecular Biology Journal ISSN 2471-8084. DOI: 10.21767/2471-8084.100057

Jia Y, Ohanyan A, Lue YH, Swerdloff RS, Liu PY, Cohen P, Wang C. The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs. Apoptosis. 2015 Apr;20(4):551-61. doi: 10.1007/s10495-015-1105-5. PMID: 25666707; PMCID: PMC4351164.

Zapała B, Staszel T, Kieć-Wilk B, Polus A, Knapp A, Wybrańska I, Kaczyński Ł, Dembińska-Kieć A. Humanin and its derivatives as peptides with potential antiapoptotic and confirmed neuroprotective activities. Przegl Lek. 2011;68(7):372-7. Polish. PMID: 22010475. 

Zapała B, Kaczyński Ł, Kieć-Wilk B, Staszel T, Knapp A, Thoresen GH, Wybrańska I, Dembińska-Kieć A. Humanins, the neuroprotective and cytoprotective peptides with antiapoptotic and anti-inflammatory properties. Pharmacol Rep. 2010 Sep-Oct;62(5):767-77. doi: 10.1016/s1734-1140(10)70337-6. PMID: 21098860.

Yamagishi Y, Hashimoto Y, Niikura T, Nishimoto I. Identification of essential amino acids in Humanin, a neuroprotective factor against Alzheimer's disease-relevant insults. Peptides. 2003 Apr;24(4):585-95. doi: 10.1016/s0196-9781(03)00106-2. PMID: 12860203.

Arakawa T, Hirano A, Shiraki K, Niikura T, Kita Y. Advances in characterization of neuroprotective peptide, humanin. Curr Med Chem. 2011;18(36):5554-63. doi: 10.2174/092986711798347261. PMID: 22172065.

Yen K, Wan J, Mehta HH, Miller B, Christensen A, Levine ME, Salomon MP, Brandhorst S, Xiao J, Kim SJ, Navarrete G, Campo D, Harry GJ, Longo V, Pike CJ, Mack WJ, Hodis HN, Crimmins EM, Cohen P. Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans. Sci Rep. 2018 Sep 21;8(1):14212. doi: 10.1038/s41598-018-32616-7. PMID: 30242290; PMCID: PMC6154958.

Jung SS, Van Nostrand WE. Humanin rescues human cerebrovascular smooth muscle cells from Abeta-induced toxicity. J Neurochem. 2003 Jan;84(2):266-72. doi: 10.1046/j.1471-4159.2003.01524.x. PMID: 12558989.

Nguyen, T.T., Wei, S., Nguyen, T.H. et al. Mitochondria-associated programmed cell death as a therapeutic target for age-related disease. Exp Mol Med 55, 1595–1619 (2023). https://doi.org/10.1038/s12276-023-01046-5

Charununtakorn ST, Shinlapawittayatorn K, Chattipakorn SC, Chattipakorn N. Potential Roles of Humanin on Apoptosis in the Heart. Cardiovasc Ther. 2016 Apr;34(2):107-14. doi: 10.1111/1755-5922.12168. PMID: 26667157.

Yen K, Lee C, Mehta H, Cohen P. The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol. 2013 Jan 11;50(1):R11-9. doi: 10.1530/JME-12-0203. PMID: 23239898; PMCID: PMC3705736.

Ramanjaneya M, Bettahi I, Jerobin J, Chandra P, Abi Khalil C, Skarulis M, Atkin SL, Abou-Samra AB. Mitochondrial-Derived Peptides Are Down Regulated in Diabetes Subjects. Front Endocrinol (Lausanne). 2019 May 31;10:331. doi: 10.3389/fendo.2019.00331. PMID: 31214116; PMCID: PMC6554664. 

Alirezaee A, Safari F, Aliyari R, Einollahi N. A Review on Therapeutic Effects of Humanin, a New Peptide in Treatment of Type II Diabetes. 3 2015; 7 (28) :56-62
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