NMM Human
Description
Chemical Identity of NMM
NMM (C7H16N4O2) is a peptide-linked chemical component classified under the Protein Data Bank Japan (PDB) as an L-peptide linking molecule. Key characteristics include:
| Property | Value |
|---|---|
| Formula | C₇H₁₆N₄O₂ |
| Molecular Weight | 188.228 g/mol |
| Formal Charge | 0 |
| Parent Compound | Arginine (ARG) |
| Three-Letter Code | NMM |
NMM is structurally distinct from NMN (nicotinamide mononucleotide), which has the formula C₁₁H₁₅N₃O₈P and serves as an NAD⁺ precursor.
NMN: A Key NAD⁺ Precursor in Human Research
While NMM lacks documented human studies, NMN has been extensively researched. Below is a synthesis of critical findings:
Mechanism of Action
NMN is directly converted to NAD⁺ via enzymatic pathways, enhancing cellular energy metabolism and mitochondrial function . It is one of five NAD⁺ precursors (tryptophan, nicotinamide, nicotinic acid, nicotinamide riboside, and NMN), with NMN being a late-stage precursor .
Dose-Dependent Efficacy
A 2022 randomized, double-blind trial (NCT04823260) evaluated NMN doses (300 mg, 600 mg, 900 mg/day) in 80 middle-aged adults over 60 days. Key outcomes:
| Parameter | 300 mg | 600 mg | 900 mg | Placebo |
|---|---|---|---|---|
| Blood NAD⁺ Increase (Day 30) | ✅ | ✅ | ✅ | ❌ |
| 6-Minute Walk Improvement | 24% | 50% | 50% | 2% |
| Biological Age Stabilization | ✅ | ✅ | ✅ | ❌ |
Key Findings:
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All NMN doses significantly elevated NAD⁺ levels.
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Higher doses (600–900 mg/day) showed maximal benefits in physical performance and biological age metrics.
Target Populations and Effects
Limitations:
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Human trials show milder effects compared to animal models, likely due to strict NAD⁺ homeostasis in humans .
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Current trials are short-term (3–12 weeks), limiting long-term safety assessment .
NMM vs. NMN: Distinction in Context
| Aspect | NMM | NMN |
|---|---|---|
| Function | Peptide linkage (ARG derivative) | NAD⁺ precursor |
| Human Trials | None documented | Extensive (safety/tolerability) |
| Biological Role | Structural component in proteins | Metabolic regulator |
Future Research Directions
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Dose Optimization: Higher NMN doses (>900 mg/day) to explore maximal NAD⁺ elevation .
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Longitudinal Studies: Extended trials to assess chronic effects on aging biomarkers (e.g., telomere length) .
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Mechanistic Insights: Clarifying NMN’s role in insulin resistance, mitochondrial function, and epigenetic regulation .
Product Specs
Q&A
What physiological pathways are involved in NMN metabolism in humans?
NMN functions primarily through the NAD+ biosynthesis pathway. Once administered, NMN can either be transported directly into cells via the Slc12a8 transporter or converted to nicotinamide riboside (NR) before entering cells. After cellular entry, NMN is converted back to NAD+ through enzymatic processes. Research indicates that the small intestine shows approximately 100-fold higher expression of the Slc12a8 transporter compared to brain or adipose tissue, suggesting differential absorption capabilities across tissue types . Methodologically, researchers should consider tissue-specific differences when designing NMN administration protocols and measuring NAD+ biosynthesis outcomes.
How does NMN supplementation influence age-related biomarkers in human subjects?
NMN supplementation has demonstrated effects on multiple age-related biomarkers. Human studies suggest that NMN may improve metabolic profiles, with preliminary evidence indicating it can enhance lipid profiles and energy metabolism. Researchers have documented improvements in markers resembling profiles of individuals 10-20 years younger following NMN administration . When designing studies, researchers should incorporate comprehensive biomarker panels including metabolic (glucose regulation, lipid profiles), inflammatory (cytokine profiles), and molecular (NAD+ levels, SIRT1 activity) measurements to fully characterize NMN's effects.
What are the primary considerations for NMN stability in human research protocols?
NMN stability is a critical methodological consideration that can significantly impact experimental outcomes. Researchers should implement stability testing protocols including temperature variation assessments, pH sensitivity analyses, and degradation monitoring in both storage and physiological conditions. When preparing NMN for human studies, consideration should be given to encapsulation methods that mimic the body's natural extracellular vesicle transport system, as research suggests that adipose-derived extracellular vesicles naturally transport NMN in the plasma .
How should researchers differentiate between NMN's direct effects and those mediated by NAD+ metabolism?
To differentiate between direct NMN effects and NAD+-mediated outcomes, researchers should implement time-course experiments capturing both rapid responses (potentially direct NMN effects) and delayed responses (likely NAD+-dependent). Methodologically, this requires:
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Temporal profiling of NMN, NR, and NAD+ concentrations in target tissues
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Parallel inhibition studies using specific pathway blockers
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Selective knockout or knockdown of key enzymes in NAD+ biosynthesis pathways
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Comparative analysis with direct NAD+ supplementation
Research indicates that eNAMPT (extracellular nicotinamide phosphoribosyltransferase) levels decline with age, similar to NAD+ and NMN levels , suggesting interplay between these molecules that must be accounted for in experimental designs.
What experimental approaches best capture tissue-specific NMN transport mechanisms in human subjects?
Current research identifies Slc12a8 as a primary NMN transporter with differential expression across tissues . To effectively study tissue-specific transport:
| Methodological Approach | Application in Human Studies | Technical Considerations |
|---|---|---|
| PET/CT imaging with labeled NMN | Non-invasive tissue distribution tracking | Requires stable isotope labeling without altering transport properties |
| Tissue biopsy with transporter quantification | Direct measurement of transporter expression | Limited to accessible tissues; multiple timepoints challenging |
| Ex vivo human tissue culture models | Controlled transport studies with human tissues | May not fully recapitulate in vivo conditions |
| Single-cell RNA sequencing | Cell-specific transporter expression profiling | Requires careful sample processing to maintain RNA integrity |
Researchers should be particularly attentive to intestinal absorption mechanisms, as data suggests uniquely high Slc12a8 expression in the small intestine, potentially related to gut microbiome interactions .
How should age-dependent variations in NMN metabolism be incorporated into human research protocols?
Age-related changes in NMN metabolism present critical methodological challenges. Research indicates that aging compromises the conversion of NMN to NAD+ , and older subjects may show different responsiveness to NMN supplementation compared to younger cohorts. Rigorous research design should include:
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Age-stratified cohort analysis with matched controls
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Baseline NAD+ metabolism profiling before intervention
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Measurement of key enzymes involved in NAD+ biosynthesis across age groups
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Dosage optimization protocols specific to age demographics
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Extended monitoring periods for older subjects to capture delayed metabolic responses
Interestingly, some studies suggest older mice are more responsive to NMN compared to young mice , highlighting the importance of not assuming uniform response patterns across age demographics.
What methodologies effectively measure human biological responses to NMN in rehabilitation settings?
When assessing NMN effects in rehabilitation contexts, researchers should employ multi-modal measurement approaches:
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Quantitative assessment of human-robot interaction forces using precision torque sensors (<120 Nmm sensitivity)
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Continuous monitoring of physiological parameters during rehabilitation exercises
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Real-time disturbance observation techniques to distinguish between mechanical interactions and biological responses
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Implementation of zero-impedance control protocols to minimize resistance forces during passive movements
These approaches allow researchers to differentiate between mechanical assistance effects and biological enhancement from NMN supplementation in rehabilitation scenarios.
How can researchers optimize experimental designs to account for variability in human-NMN interactions?
Human variability represents a significant challenge in NMN research. Methodologically sound approaches include:
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Adaptive experimental protocols that adjust to individual metabolic response patterns
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Implementation of crossover designs with washout periods calibrated to NMN metabolism rates
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Continuous monitoring rather than discrete sampling to capture temporal variability
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Development of personalized biomarker response profiles
Research indicates significant inter-individual differences in NAD+ metabolism , necessitating personalized analytical approaches rather than population-averaged methods.
What statistical approaches best address the multi-factorial nature of NMN effects in human studies?
NMN's diverse physiological effects require sophisticated analytical approaches:
| Statistical Method | Application in NMN Research | Advantages |
|---|---|---|
| Mixed-effects modeling | Accounting for individual response variations | Incorporates both fixed and random effects of NMN supplementation |
| Time-series analysis | Temporal patterns in NAD+ biosynthesis | Captures dynamic metabolic responses |
| Network pharmacology | Pathway interconnections in NMN metabolism | Maps systemic effects beyond direct NAD+ conversion |
| Bayesian hierarchical modeling | Integration of prior metabolic knowledge | Handles uncertainty in biological variability |
Researchers should avoid simplistic pre-post comparisons that fail to capture the complex temporal and tissue-specific nature of NMN metabolism.
How should researchers interpret conflicting results between animal and human NMN studies?
The translation gap between murine and human NMN research requires methodological caution. While NMN has demonstrated remarkable effects in mice—including suppression of age-associated weight gain, enhanced insulin sensitivity, and protection against neurodegeneration —human outcomes may differ. Researchers should:
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Develop allometric scaling protocols specific to NAD+ metabolism
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Account for species-specific differences in NMN transport mechanisms
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Consider evolutionary divergence in NAD+-dependent signaling pathways
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Implement parallel human-mouse experimental designs with matched protocols
Current human research, while promising, remains preliminary compared to extensive mouse studies . Researchers should maintain scientific skepticism when extrapolating from murine models to human applications.
What methodological approaches effectively measure the influence of NMN on human inflammaging processes?
To study NMN's effects on age-related inflammation, researchers should implement multi-level analytical frameworks:
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Cytokine profiling focused on both pro-inflammatory and anti-inflammatory markers
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Tissue-specific inflammation assessment, particularly in adipose tissue where NMN has shown significant anti-inflammatory effects
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Epigenetic profiling of inflammation-associated genes and their response to NMN
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Integrated immune cell functional assays rather than simple enumeration
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Longitudinal monitoring protocols to capture delayed immune modulation effects
Research indicates that older subjects may show differential inflammatory responses to NMN compared to younger cohorts , underscoring the importance of age-stratified analysis in inflammaging research.
What emerging technologies will advance precision in human NMN research?
Several cutting-edge methodologies show promise for enhancing NMN human research:
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Single-cell metabolomics to capture cellular heterogeneity in NAD+ metabolism
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Wearable biosensors for continuous NAD+ metabolite monitoring
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AI-guided adaptive dosing protocols responding to individual metabolic profiles
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Microbiome interaction analysis to understand gut-mediated effects of NMN
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Advanced liposomal delivery systems mimicking natural extracellular vesicle transport
These approaches will help address current limitations in understanding individual variability in NMN responses.
How should researchers design protocols to distinguish therapeutic versus preventive effects of NMN in humans?
Differentiating between NMN's therapeutic and preventive capabilities requires nuanced methodological approaches:
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Long-term longitudinal studies with predefined disease progression markers
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Risk-stratified cohort selection based on genetic and environmental factors
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Intervention timing studies comparing early versus late NMN administration
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Biomarker trajectory analysis rather than single timepoint assessments
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Combination protocols comparing NMN alone versus NMN with standard interventions
Current research suggests multifaceted effects of NMN that may span both therapeutic and preventive domains , necessitating carefully designed studies to distinguish these effects.
Product Science Overview
Non-Muscle Myosin-II (NMII) is a crucial molecular motor involved in various cellular processes. It is a part of the myosin superfamily, which consists of actin-based molecular motors that convert chemical energy into mechanical work. NMII is particularly significant in non-muscle cells, where it plays a vital role in cell adhesion, migration, and division.
NMII is a hexamer composed of two heavy chains, two essential light chains (ELCs), and two regulatory light chains (RLCs) . The regulatory light chains are approximately 20 kDa in size and are critical for the regulation of NMII activity. The heavy chains form the backbone of the molecule, while the light chains modulate its function.
The motor activity of NMII involves binding to F-actin, hydrolysis of ATP, and a resulting power stroke. This process is known as the myosin mechanochemical cycle or the cross-bridge cycle . The regulatory light chains play a pivotal role in this cycle by modulating the interaction between the myosin heads and actin filaments. Phosphorylation of the RLCs is a key regulatory mechanism that controls NMII activity .
NMII is involved in a plethora of cellular processes, including:
- Cell Migration: NMII generates contractile forces that drive cell movement.
- Cytokinesis: During cell division, NMII helps in the formation of the contractile ring, which is essential for the separation of daughter cells.
- Epithelial Barrier Function: NMII contributes to the maintenance of tight junctions and the integrity of epithelial layers.
- Tissue Morphogenesis: NMII is involved in shaping tissues during development by regulating cell shape and movement .
The human recombinant NMII regulatory light chain is a biotechnologically produced version of the natural protein. It is used in various research applications to study the function and regulation of NMII. Recombinant proteins are produced using genetic engineering techniques, where the gene encoding the protein is inserted into an expression system, such as bacteria or yeast, to produce large quantities of the protein.
Research on NMII and its regulatory light chains has provided significant insights into the molecular mechanisms underlying various cellular processes. Advanced imaging technologies and biophysical approaches have revealed new aspects of NMII assembly and function . The human recombinant NMII regulatory light chain is a valuable tool in these studies, allowing researchers to dissect the specific roles of RLCs in NMII regulation.
