Humanin is a microprotein encoded within the mitochondrial DNA. It's thought to act as a cytoprotective agent, helping cells survive under stress. It's unique among Anti-Aging & Longevity peptides because it originates within the mitochondria itself. One study showed that Humanin levels decline with age, suggesting a potential link to age-related decline (Miller et al., 2022).
This peptide isn't just a structural component; it actively communicates with the cell. Humanin interacts with specific receptors and signaling pathways, influencing cellular processes related to inflammation, apoptosis (programmed cell death), and overall cellular health. The potential of Humanin lies in its ability to modulate these core biological functions.
How Humanin Works
Humanin exerts its effects through several key mechanisms. One of the most well-studied is its interaction with the cMET receptor. The cMET receptor is a tyrosine kinase receptor involved in cell growth, survival, and motility. By binding to cMET, Humanin can activate downstream signaling pathways that promote cell survival and protect against apoptosis.
Another important pathway influenced by Humanin is the JAK/STAT3 pathway. This pathway is involved in a wide range of cellular processes, including cell growth, differentiation, and immune responses. Activation of JAK/STAT3 by Humanin can lead to increased expression of anti-apoptotic proteins and reduced inflammation, contributing to its cytoprotective effects.
Humanin can also modulate insulin sensitivity. It appears to enhance the action of insulin, potentially improving glucose metabolism. While the precise mechanisms are still under investigation, this effect may involve increased insulin receptor signaling and improved glucose uptake by cells. This may be related to its potential anti-diabetic effects (Kal et al., 2024).
What the Research Actually Shows
Neuroprotection: A study published in Alzheimer's Research & Therapy (Delgado-Peraza et al., 2023) examined the effects of exercise on neuron-derived extracellular vesicles (NDEVs) in the blood of individuals with Alzheimer's disease. While the study didn't directly administer Humanin, it found that exercise increased the levels of certain proteins within NDEVs, suggesting a potential neuroprotective effect. Evidence Grade: Preliminary (Indirect, exercise-induced changes)
Reproductive Function: Research in Biochimica et Biophysica Acta (BBA) - General Subjects (Lei & Rao, 2022) explores Humanin's role in reproduction. The review suggests Humanin may play a role in regulating various aspects of reproduction, including ovarian function and embryonic development. Evidence Grade: Preliminary (Review, primarily animal studies)
Mitochondrial Function and Aging: A review in Aging Cell (Burtscher et al., 2023) discusses the broader role of mitochondrial stress and mitokines (including Humanin) in aging. The authors point out that mitochondrial dysfunction is a hallmark of aging and that mitokines like Humanin may act as signaling molecules to communicate mitochondrial stress to the rest of the cell. Evidence Grade: Preliminary (Review, general overview)
Senescence: A study in Rejuvenation Research (Mendelsohn & Larrick, 2018) found that mitochondrial-derived peptides (MDPs), including Humanin, may exacerbate senescence under certain conditions. This suggests a complex role for Humanin in aging, where it may be beneficial in some contexts but detrimental in others. Evidence Grade: Preliminary (In vitro study)
Metabolic Regulation: A review in Peptides (Kal et al., 2024) discusses the anti-diabetic functions and evolutionary perspectives of mitochondrial-derived peptides (MDPs), including Humanin. The review suggests that Humanin may play a role in regulating glucose metabolism and insulin sensitivity. Evidence Grade: Preliminary (Review)
Humanin vs. MOTS-c
Both Humanin and MOTS-c are mitochondrial-derived peptides (MDPs) with potential anti-aging and metabolic benefits, but they differ in their primary mechanisms of action. Humanin mainly interacts with the cMET receptor and the JAK/STAT3 pathway to promote cell survival and reduce inflammation. MOTS-c, on the other hand, primarily affects metabolism by targeting AMPK, a key regulator of energy balance. AMPK activation improves insulin sensitivity and glucose metabolism.
While both peptides originate from mitochondria, their downstream effects are distinct. Humanin appears to have a broader cytoprotective effect, while MOTS-c is more specifically focused on metabolic regulation. Stacking them could offer synergistic benefits by addressing both cellular stress and metabolic dysfunction, although this is purely theoretical and not yet proven in clinical trials. A common stack would include Humanin, MOTS-c, Epitalon, and GHK-Cu.
The Honest Limitations
Much of the research on Humanin is still in the early stages. While there are promising findings from in vitro (cell culture) and animal studies, human clinical trials are limited. This makes it difficult to definitively determine its efficacy and safety in humans.
The specific dosages and administration protocols for Humanin are not yet well-established. Most studies have used varying concentrations in vitro or in animal models, and it's unclear how these translate to optimal human dosing. Furthermore, the long-term effects of Humanin supplementation are unknown. Most studies have been relatively short-term, and there is a need for longer-term studies to assess potential risks and benefits.
The potential for Humanin to exacerbate senescence under certain conditions, as suggested by Mendelsohn & Larrick (2018), also warrants further investigation. It's important to understand the specific contexts in which Humanin may be beneficial versus detrimental.
Sourcing High-Quality Humanin
Given the limited regulation of the peptide market, it's crucial to source Humanin from a reputable supplier. Look for suppliers that provide third-party testing and Certificates of Analysis (COAs) to verify the purity and identity of their products. A COA should confirm that the product contains the stated amount of Humanin and is free from contaminants. Be wary of suppliers that make exaggerated claims or lack transparency about their sourcing and testing practices. It's often worth paying a premium for a product that has been rigorously tested and verified. Also, ensure the Humanin is lyophilized (freeze-dried) and stored properly to maintain its stability. You can use our peptide dosage calculator to properly measure your dose.