Humanin

Introduction to Humanin

Humanin is a remarkable mitochondrial-derived peptide (MDP) that has garnered significant attention for its diverse roles in cellular health and disease prevention. Mitochondrial peptides, such as humanin and MOTS-c, are a class of bioactive molecules produced within mitochondria that play crucial roles in cellular stress responses, apoptosis regulation, and maintaining mitochondrial health. Encoded within the mitochondrial genome, humanin is produced from a short open reading frame and is highly conserved across chordate species, underscoring its evolutionary importance as an ancient mitochondrial signal. In contrast to the nuclear genome, which encodes most mammalian mitochondrial proteins, humanin is one of the few peptides encoded by mitochondrial DNA itself, highlighting the complexity of mitochondrial-nuclear interactions. The evolutionary importance of humanin is further emphasized by the role of mammalian mitochondrial proteins in mitochondrial function, dynamics, and quality control. As a mitochondrial derived peptide, humanin is involved in regulating critical cellular processes such as apoptosis, insulin sensitivity, and the modulation of inflammatory markers. Cohen P is recognized as a leading researcher in the field of mitochondrial peptides and aging, contributing significantly to our understanding of the molecular mechanisms that influence lifespan.

Research using humanin transgenic mice has provided valuable insights into its physiological functions. These mice exhibit unique phenotypes, including reduced body length, body weight, and litter size, which mirror some effects observed in other model organisms like C. elegans. Notably, humanin has demonstrated a protective effect against toxic insults, such as cyclophosphamide-induced male germ cell apoptosis, highlighting its role in protecting germ cells and safeguarding reproductive health. Furthermore, humanin’s influence on insulin sensitivity positions it as a potential modulator of metabolic health, while its ability to regulate inflammatory markers suggests a broader impact on immune function and chronic disease prevention. Importantly, humanin levels generally decline with age across multiple species, and this decrease is associated with aging-related diseases such as Alzheimer’s and MELAS, suggesting that maintaining or increasing humanin levels may be linked to improved healthspan and lifespan.

Overall, the mitochondrial derived peptide humanin stands out as a key player in maintaining cellular homeostasis, protecting germ cells, and supporting metabolic and immune health through its actions at the mitochondrial level. The integrity and composition of mitochondrial membranes are crucial for the proper localization and function of humanin, influencing its neuroprotective and metabolic effects.

Potential Health Benefits of Humanin in Oxidative Stress

1. It has been implicated in protecting neurons from various stresses, with the humanin peptide exerting neuroprotective effects by interacting with specific membrane receptors such as the trimeric receptor complex (CNTFR, WSX-1, gp130) and FPR2, potentially offering therapeutic benefits for neurodegenerative diseases. The HN peptide is also recognized for its antiapoptotic properties, contributing to its neuroprotective function.
2. Humanin may possess anti-inflammatory properties, which could be beneficial in mitigating inflammation-related conditions.
3. It has been demonstrated to inhibit cell death pathways, specifically by inhibiting the mitochondrial apoptotic pathway and reducing cell apoptosis, including in tunel positive cells, suggesting a role in promoting cell survival and tissue integrity. These properties make humanin a promising target for therapeutic research.

Derived peptide humanin protects various cell types from oxidative stress and apoptosis. Additionally, humanin has been shown to protect human retinal pigment epithelial cells from oxidative damage.

Key Takeaways of Humanin Guide 2025

1. Humanin shows promising multifaceted therapeutic potential across neurodegenerative, metabolic, cardiovascular disorders, and cancer, though further clinical trials are necessary to validate its efficacy. Notably, levels of humanin have been associated with health status and disease risk in various studies.
2. Humanin’s therapeutic effects are mediated through receptor interactions, signaling pathways like PI3K/Akt, and mitochondrial stabilization, influencing gene expression related to mitochondrial and cellular health, enhancing cell survival and potentially benefiting various health conditions.
3. Humanin offers versatile administration options including intravenous, subcutaneous, oral formulations, and nasal sprays/drops, potentially enhancing accessibility and effectiveness in therapeutic applications.
4. Humanin is primarily used in specific health conditions like cognitive decline, diabetes, cardiovascular disease, and triple negative breast cancer, but caution is needed due to potential contraindications such as allergies, pregnancy, severe chronic diseases, autoimmune disorders, and uncontrolled medical conditions.
5. Humanin is generally well-tolerated, but individuals should be mindful of potential mild gastrointestinal and systemic side effects, seeking medical advice if symptoms persist.

What is the mitochondrial derived peptide Humanin

A mitochondrial-derived peptide, humanin (HN), consisting of 24 amino acids, works quite miraculously. It is one of several recently discovered mitochondrial peptides with important biological functions. It is known for its neuroprotective and cytoprotective properties.

The peptide’s ability to protect cells from stress-induced injury and inhibit apoptotic pathways makes it useful in neurodegenerative disorders like Alzheimer’s disease, where cell death induced by amyloid-beta peptides is a hallmark. Therefore, humanin works as a rescue factor abolishing neuronal cell death and preserving neuronal functions by preventing cell death induced by neurodegenerative factors. The effect of HN has also been demonstrated in experimental models of neurodegenerative disease, where it reduces neuronal loss and improves cellular survival.

Besides its neuroprotective functions, HN exerts potential benefits in metabolic disorders like diabetes mellitus and cardiovascular diseases by maintaining cardiac mitochondrial function and supporting mitochondrial bioenergetics. Nonetheless, more clinical trials are needed to determine its efficacy and therapeutic role in human cells. Key studies published in Proc Natl Acad Sci have advanced understanding of humanin and its biological significance.

How Does Humanin Work in Mitochondrial Function?

Humanin works in various ways to exert its therapeutic role in different health conditions. Primarily, humanin interacts with target cells and exerts its effects through multiple mechanisms.

Humanin binds certain protective membrane receptors like formyl peptide receptor-like 1 (FPRL1) and the ciliary neurotrophic factor receptor (CNTFR), mediating humanin’s cytoprotective and signaling effects. These receptors increase cell survival in stressful conditions and damage. In addition, humanin interacts with growth factor binding proteins such as IGFBP3, which modulate its effects on apoptosis and metabolic regulation.

The peptide also activates signaling cascades like PI3K/Akt, which play an important role in inhibiting programmed cell death, thereby prolonging the lifespan of cells, especially cortical neurons. Humanin inhibits the mitochondrial apoptotic pathway by interacting with key proteins involved in mitochondrial-mediated cell death.

Therefore, humanin peptide suppresses apoptosis, which is particularly helpful in age-related diseases.

Being a mitochondrial-derived peptide, humanin helps stabilize mitochondrial membrane potential and reduces oxidative stress by decreasing reactive oxygen species. The integrity and composition of mitochondrial membranes play a key role in humanin’s function and its ability to protect mitochondrial health. This is crucial for energy production and cell survival, helping prevent neuronal cell death. Humanin belongs to a broader family of mitochondrial peptides, which are involved in cellular signaling, stress responses, and maintaining mitochondrial health. By supporting energy production, humanin also contributes to mitochondrial bioenergetics, enhancing cellular energy metabolism and resilience.

Chemical Structure of Humanin

Research on Humanin in Humanin Transgenic Mice

The humanin gene is encoded within mitochondrial DNA and is highly conserved across species, functioning as an ancient mitochondrial signal. Endogenous hn is naturally expressed in various cells and tissues, where its regulation is linked to biological functions such as cellular stress responses, mitochondrial health, aging, and disease mechanisms.

1. Humanin exhibits a high level of cortical rescue activity leading to neuroprotective effects.
2. One human experimental model suggests that the HNGF6A analog of humanin plays a therapeutic role in diseases such as diabetes.
3. Recent studies suggest that humanin may play a beneficial role in Parkinson’s disease due to its mitochondrial membrane stabilizing properties.
4. Studies report that humanin can improve cognition in mice with induced intracerebral hemorrhage, proving its role in brain recovery. Some studies specifically use male mice to assess the protective effects of humanin against male germ cell apoptosis, and demonstrate that humanin protects germ cells from various stressors.
5. Research suggests that humanin can help improve object memory by increasing acetylcholine levels in the hippocampus.
6. Humanin is known to increase insulin sensitivity and enhance pancreatic β cell survival, leading to therapeutic efficacy in diabetes mellitus.
7. Humanin exhibits a proapoptotic activity of TNF-alpha in tumor cells. Studies often use specific murine and human breast cancer cell lines, such as 4T1, MCF7, T47D, and MDA-MB-231, to investigate humanin’s effects on apoptosis and survival. Humanin is also overexpressed in pituitary tumor cells compared to normal pituitary tissue, suggesting a potential role in tumorigenesis and resistance to apoptosis. This suggests a potential role of humanin in cancer treatment. Additionally, enhancing chemotherapy induced suppression of tumor growth has been observed with humanin administration in preclinical models. In male mice, studies on male germ cells have shown that humanin provides cytoprotective effects and prevents apoptosis during injury or chemotherapy.

Humanin and Healthspan: Implications for Longevity and Aging

Humanin, a mitochondrial derived peptide, has emerged as a significant factor in the quest to extend healthspan—the period of life spent in good health, free from chronic disease and disability. Research has shown that humanin plays a pivotal role in supporting longevity by enhancing the body’s resilience to age-related diseases and cellular stressors.

Studies involving humanin transgenic mice have provided compelling evidence for humanin’s impact on healthspan. These mice display improved metabolic health, marked by better regulation of glucose and lipid metabolism, and a notable reduction in oxidative stress. By minimizing the damaging effects of reactive oxygen species, humanin helps preserve mitochondrial function, which is essential for maintaining cellular energy and vitality as organisms age.

One of the key protective mechanisms of the humanin peptide is its ability to suppress apoptosis, or programmed cell death. This function is especially critical in tissues vulnerable to age-related decline, such as neuronal cells in the brain and pancreatic beta cells responsible for insulin production. By promoting cell survival in these vital cell types, humanin contributes to the prevention of neurodegenerative conditions like Alzheimer’s disease and supports metabolic health, reducing the risk of insulin resistance and diabetes.

Furthermore, humanin’s protective effects extend to cardiovascular health. By safeguarding cardiac cells from oxidative stress and apoptosis, humanin helps reduce the incidence and severity of cardiovascular disease, a leading cause of morbidity in older adults. Its broad cytoprotective actions make it a promising candidate for interventions aimed at delaying the onset of age related diseases and enhancing overall healthspan.

In summary, the mitochondrial derived peptide humanin stands out as a key modulator of longevity, working at the cellular level to combat oxidative stress, support metabolic and cardiovascular health, and promote the survival of critical cell populations. Ongoing research continues to explore how boosting humanin levels or mimicking its actions could pave the way for novel therapies to extend healthy years of life.

How is Humanin administered?

Humanin is versatile in its modes of administration, available in various formulations.

Common administration methods include intravenous, subcutaneous, and intraperitoneal injections. Intravenous injection delivers the peptide directly into the bloodstream for rapid absorption and maximum efficacy.

Subcutaneous administration involves injecting into fatty tissue beneath the skin for steady, prolonged release. Intraperitoneal administration is primarily used in animal studies.

Humanin is also available in oral formulations and nasal sprays/drops, offering non-invasive options.

Potential Candidates for Humanin Treatment

Humanin is primarily used for elderly individuals with cognitive decline or neurodegenerative disorders like Alzheimer’s disease and dementia. Age and humanin levels are inversely correlated, with humanin concentrations declining as people age.

Individuals with diabetes and insulin resistance may benefit from humanin due to its effects on insulin sensitivity and enhancing pancreatic β cell function. The peptide also helps maintain metabolic homeostasis in diabetics. Humanin supports cardiovascular health by maintaining cardiac mitochondrial function, making it useful in cardiovascular disorders. Humanin and related peptides may protect against age-related macular degeneration by supporting retinal pigment epithelium (RPE) cells.

In Alzheimer’s disease, familial Alzheimer’s disease genes are important risk factors that may interact with humanin pathways.

Contraindications for humanin include:

1. Allergic reactions
2. Pregnancy and breastfeeding
3. Severe chronic diseases such as chronic kidney disease
4. Autoimmune disorders, including pancreatic β cell dysfunction
5. Uncontrolled medical conditions

Humanin as a Neuroprotective and Cytoprotective Peptide

Humanin is a 24-amino acid mitochondrial-derived peptide released by astrocytes and other cells in response to stress. As one of the identified mitochondrial derived peptides, humanin represents a new class of bioactive molecules. These mitochondrial peptides are produced within mitochondria and play key roles in cellular stress responses, apoptosis regulation, and maintaining mitochondrial health. Humanin exhibits neuroprotective effects by interacting with specific cell surface receptors to activate pathways that enhance cell survival, reduce oxidative stress, and protect against apoptosis; the HN peptide is particularly noted for its antiapoptotic properties and its role in preventing cell death due to oxidative stress and neurodegenerative conditions.

Humanin’s ability to preserve mitochondrial function and regulate inflammatory responses makes it a promising therapeutic candidate for neurodegeneration, cardiovascular diseases, metabolic disorders, and aging-related cellular damage. It also supports mitochondrial bioenergetics, influencing cellular energy production and metabolic regulation. It is recognized as a mitochondrial protein affecting lifespan in various species. Endogenous humanin levels are regulated within the body and may serve as biomarkers of cellular stress and injury.

Humanin Side Effects

Humanin is generally well-tolerated, with mild side effects primarily gastrointestinal in nature. Potential side effects include:

• Injection site reactions
• Allergic reactions
• Nausea and vomiting
• Headache
• Fatigue

It is important to consult a healthcare professional if symptoms persist.

Humanin Dosage

Due to limited clinical research, humanin dosing regimens are not well-established. Research studies often use doses ranging from 0.1 mg/kg to 10 mg/kg.
For humans, subcutaneous or intravenous administration of 2 mg to 10 mg of humanin per day is common.
Consult a healthcare professional to determine the appropriate dose.

Humanin Cost

Humanin cost varies depending on brand, strength, dosage formulation and compounding pharmacy making it. It is currently not commercially available.

Humanin vs Bendavia (SS-31)

Both humanin and Bendavia (SS-31) are neuroprotective peptides but differ in composition, mode of action, side effects, and administration.

Humanin, a member of the mitochondrial peptides family, primarily acts via cell surface receptors to broadly promote cell survival and mitochondrial protection, while SS-31 directly targets mitochondrial proteins involved in bioenergetics and energy production, thereby improving mitochondrial bioenergetics.

Both show promise in neuroprotection, with SS-31 particularly suited for mitochondrial dysfunction-related conditions like cardiovascular diseases and ischemic injuries.

Conclusion

Humanin is a mitochondrial-derived peptide with significant roles in regulating apoptosis, enhancing insulin sensitivity, and modulating inflammatory markers. Its overexpression is linked to increased lifespan in model organisms, and it protects cells from stress and toxic insults. Circulating humanin levels decline with age but remain stable in long-lived species like the naked mole-rat. Higher humanin levels in offspring of centenarians suggest a connection to longevity.

Humanin’s therapeutic potential spans age-related diseases including triple negative breast cancer, cardiovascular disease, and Alzheimer’s disease. Studies highlight its involvement in tumor cell survival and chemoresistance, emphasizing its relevance in cancer research. Its role in metabolic and cardiovascular health further underscores clinical promise. Ongoing research into humanin’s mechanisms and impact on inflammatory markers will be crucial for developing novel therapies aimed at lifespan extension and age-related disease management.