Protocols · Longevity
Humanin dosage protocol
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Dosage protocol
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Humanin: research background
What the compound is
Humanin is a 24-amino-acid peptide encoded by mitochondrial DNA, classifying it as a mitochondrial-derived peptide (MDP). It functions as a signaling molecule, or mitokine, enabling communication of mitochondrial stress between cells and tissues (PMID 36642986, PMID 37106758, PMID 38132360). Humanin has been identified in various tissues, including brain tissue of patients with familial Alzheimer's disease (PMID 35104624).
How it is thought to work
Humanin is known to be a cytoprotective factor that preserves mitochondrial function and cell viability under stressful conditions, including cellular senescence (PMID 37106758, PMID 38132360). It is thought to protect neurons from death related to Alzheimer's disease by binding to a receptor complex on the cell surface that involves CNTFRalpha, WSX-1, and gp130 (PMID 19997871). Its mechanisms include anti-apoptotic signaling cascades, involvement in the insulin signaling pathway, mitochondrial function, and autophagic activity (PMID 35104624).
What laboratory and animal studies report
In various murine (mouse) models of Alzheimer's disease, including transgenic mice expressing familial AD genes, humanin was effective against AD-related neuronal dysfunction (animal study; PMID 19997871). Humanin has been shown to protect against oxidative stress and apoptosis in buffalo spermatozoa, with 5 µM humanin supplementation leading to higher mitochondrial membrane potential and DNA integrity (animal study; PMID 36183493). However, in glioblastoma (GBM) models, nanomolar concentrations of humanin promoted temozolomide (TMZ) resistance by activating DNA damage response (DDR) and accelerated blood-tumor barrier (BTB) formation (humanized organotypic GBM model and mouse models; PMID 39053460).
Human evidence so far
In a randomized controlled trial (ADEX) involving patients with mild to moderate Alzheimer's disease, neuron-derived extracellular vesicle (NDEV) levels of humanin in plasma increased in the exercise group but remained unchanged in the control group. This effect was particularly noted in APOE ε4 carriers (human study; PMID 37730689). Such findings suggest that exercise-induced cognitive benefits might be partly mediated by the upregulation of neuroprotective factors like humanin in NDEVs (human study; PMID 37730689).
Open questions and limitations
While humanin levels are altered in aging and associated with age-related diseases, it is not yet conclusively shown whether these changes contribute to aging or represent 'rescue factors' (PMID 36642986). Further research is needed to fully understand the role of humanin in aging and disease and to identify potential interventions (PMID 37106758). The effects of exercise duration, intensity, and type on NDEV humanin levels in early AD and other neurodegenerative disorders also require further investigation (human study; PMID 37730689).
Key terms explained
Mitokines are signaling molecules that communicate local mitochondrial stress to other mitochondria in distant cells and tissues (PMID 36642986). Cellular senescence is a cellular aging process characterized by a decline in cellular functions and proliferation, leading to increased cellular damage and death (PMID 37106758). Neuron-derived extracellular vesicles (NDEVs) are small membrane-bound sacs released by neurons that can be found in the blood and may serve as biomarkers (PMID 37730689). The GP130 receptor is part of a complex that humanin can bind to, influencing cellular signaling (PMID 19997871, PMID 39053460).
Studies cited in this section
- Mitochondrial stress and mitokines in aging. — Aging cell, 2023 (PMID 36642986)
- Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer's disease. — Alzheimer's research & therapy, 2023 (PMID 37730689)
- Humanin and the receptors for humanin. — Molecular neurobiology, 2010 (PMID 19997871)
- Humanin and Its Pathophysiological Roles in Aging: A Systematic Review. — Biology, 2023 (PMID 37106758)
- Myeloid cells coordinately induce glioma cell-intrinsic and cell-extrinsic pathways for chemoresistance via GP130 signaling. — Cell reports. Medicine, 2024 (PMID 39053460)
- An evidence of Humanin-like peptide and Humanin mediated cryosurvival of spermatozoa in buffalo bulls. — Theriogenology, 2022 (PMID 36183493)
- Roles of humanin and derivatives on the pathology of neurodegenerative diseases and cognition. — Biochimica et biophysica acta. General subjects, 2022 (PMID 35104624)
- Neuroprotective Action of Humanin and Humanin Analogues: Research Findings and Perspectives. — Biology, 2023 (PMID 38132360)
Summarised from the PubMed abstracts listed above. Educational reference only — not medical advice or instructions.
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