NMN-Loaded Vesicles Prevent Skin Wrinkling and Thinning in Rodents
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Chinese researchers have developed a novel delivery system combining NMN with stem cell-derived vesicles that significantly reduced skin wrinkling, thinning, and cellular damage in a mouse model of accelerated skin ageing.
Published in Stem Cell Research and Therapy, this study from Jiangsu University demonstrates that loading NMN into small extracellular vesicles (sEVs) from human umbilical cord cells provides superior protection against skin ageing compared to either approach alone.
Key Findings
- NMN-loaded vesicles almost completely prevented wrinkle formation in chemically-induced skin ageing
- Skin thinning was significantly reduced - treated skin maintained near-normal thickness
- DNA damage in skin cells dropped dramatically to levels comparable with non-aged skin
- Cellular senescence markers decreased - fewer "zombie cells" accumulating in skin tissue
What Makes This Research Different
This wasn't a study of naturally aged skin. Instead, researchers used D-galactose, a simple sugar, to artificially accelerate skin ageing in mice. This creates ageing-like changes much faster than waiting for mice to age naturally (which takes 2-3 years).
Why D-Galactose?
When applied to skin, D-galactose induces ageing primarily through:
- Increased oxidative stress (harmful reactive molecules)
- Formation of advanced glycation end products (AGEs)
- Accelerated cellular damage and dysfunction
This method mimics some aspects of natural skin ageing whilst being much faster and more cost-effective for research purposes.
Delivery Method: Nano-Microneedles
Rather than topical creams, researchers used nano-microneedles - tiny cone-shaped structures that create microscopic channels in the skin to deliver treatments deeper into tissue. This allows better penetration than surface application.
The Vesicle Approach
Small extracellular vesicles (sEVs) are tiny bubble-like structures that cells naturally produce and release. They carry proteins, genetic material, and other molecules between cells.
Why Use Vesicles?
sEVs derived from stem cells have shown potential in tissue regeneration and protecting against UV damage. However, their effects on ageing have been limited. The researchers hypothesised that loading these vesicles with NMN might enhance both approaches.
The NMN Stability Question
One proposed advantage of this delivery system is that vesicles might stabilise NMN, protecting it from degradation. However, whether NMN actually needs this protection when taken orally or applied topically remains debated in the scientific community.
Wrinkle Prevention: Visual Results
The visual results were striking:
Control (No Treatment) Mice with D-galactose-induced skin ageing showed obvious fine wrinkles on their shaved backs.
sEVs Alone or NMN Alone Both treatments showed some benefit, reducing wrinkle severity compared to untreated aged skin. However, wrinkles were still clearly visible.
NMN-Loaded sEVs The combination treatment produced dramatically better results. Treated skin showed hardly any wrinkles, appearing almost indistinguishable from young, non-aged mouse skin.
This suggests the two approaches work synergistically - the combined effect exceeds what either treatment provides individually.
Maintaining Skin Thickness
Skin naturally thins with age as the structural layers deteriorate. The study measured this effect:
Aged Skin (Untreated) D-galactose exposure reduced skin thickness by approximately 50% - a dramatic thinning effect.
Individual Treatments Both sEVs alone and NMN alone partially prevented this thinning, maintaining intermediate thickness levels.
Combined Treatment NMN-loaded sEVs provided the strongest protection, maintaining skin thickness much closer to normal, non-aged levels.
Thicker, structurally sound skin better maintains its barrier function, mechanical properties, and youthful appearance.
Cellular Changes: DNA Damage and Senescence
Beyond visible improvements, the researchers examined what was happening at the cellular level:
DNA Damage
D-galactose exposure doubled markers of DNA damage in skin cells. This accumulated damage contributes to cellular dysfunction and ageing.
Individual treatments with either sEVs or NMN reduced DNA damage markers significantly. However, NMN-loaded sEVs reduced DNA damage to levels comparable with young, untreated skin - essentially preventing the damage entirely.
Cellular Senescence
Senescent cells are dysfunctional "zombie cells" that stop dividing but remain metabolically active, secreting inflammatory molecules that damage surrounding tissue.
The treatments reduced markers of cellular senescence, with NMN-loaded sEVs again showing the strongest effect. Fewer senescent cells mean less chronic inflammation and better tissue function.
Skin as Your Body's First Line of Defence
Skin isn't just about aesthetics. It's your body's largest organ and plays crucial protective roles:
Barrier Function Skin protects against dehydration, pathogens, UV radiation, and environmental toxins. Age-related deterioration compromises these protective functions.
Systemic Effects Recent research shows that senescent cells in skin don't just stay there - they can promote senescence in other tissues and organs. Studies have linked skin senescence to:
- Increased frailty
- Impaired skeletal muscle function
- Reduced cognitive function
- Accelerated whole-body ageing
This means interventions that slow skin ageing might have benefits beyond just skin health.
How the Treatment Works at Molecular Level
The researchers identified that NMN-loaded sEVs work through the NAD+/SIRT3 pathway, specifically affecting mitochondrial autophagy - the process by which cells remove damaged mitochondria.
NAD+ Restoration NMN boosts NAD+ levels in skin cells. NAD+ is essential for cellular energy production and activates sirtuins - proteins that regulate cellular health and stress responses.
SIRT3 Activation SIRT3 is a mitochondrial sirtuin that requires NAD+ to function. When activated, it promotes the removal of damaged mitochondria and supports healthy mitochondrial function.
Mitochondrial Quality Control By enhancing mitochondrial autophagy, the treatment helps skin cells maintain a healthy population of energy-producing mitochondria. Better mitochondrial function means healthier, more resilient skin cells.
Vesicle Benefits The sEVs themselves carry beneficial proteins and molecules that support tissue regeneration. When combined with NMN's NAD+-boosting effects, the approaches complement each other.
Research Caveats Worth Noting
Artificial Ageing Model D-galactose-induced ageing isn't identical to natural ageing. It accelerates certain aspects of ageing through specific mechanisms (oxidative stress, glycation) but doesn't perfectly replicate the complex, multifactorial process of natural skin ageing over decades.
Animal Model Mouse skin differs from human skin in structure, thickness, hair coverage, and ageing patterns. Results in mice don't automatically translate to humans.
Specialised Delivery This study used nano-microneedles, not simple oral supplementation or topical application. The delivery method itself likely affects results.
Short Duration The study examined relatively acute effects, not long-term outcomes over months or years.
Vesicle Source The vesicles came from human umbilical cord cells - a specialised source not readily available as a consumer product. This isn't something you can replicate at home.
Can You Get These Results with Oral NMN?
This study used a specialised delivery system combining NMN with stem cell vesicles delivered via microneedles. That's quite different from taking NMN orally as a supplement.
Oral NMN and Skin
Some research suggests oral NMN supplementation may benefit skin through systemic effects:
- Boosting NAD+ levels throughout the body, including skin tissue
- Supporting cellular energy metabolism
- Enhancing cellular repair processes
- Reducing oxidative stress
However, the dramatic results seen in this study likely depend on the combined vesicle delivery system rather than NMN alone.
Topical Application
Standard topical NMN application faces absorption challenges. The vesicle delivery system in this study was designed specifically to overcome these barriers.
What This Research Actually Tells Us
For Skin Health Research
This study adds to evidence that:
- NAD+ depletion contributes to skin ageing
- Restoring NAD+ levels may help maintain skin health
- Novel delivery systems might enhance supplement efficacy
- Combination approaches may work better than single interventions
For Supplement Users
Whilst you can't replicate this exact protocol at home, oral NMN supplementation may still support skin health through systemic NAD+ restoration.
Our NMN Supplement 500mg provides pharmaceutical-grade NMN that supports cellular NAD+ levels throughout your body, including skin tissue.
Realistic Expectations
Don't expect oral NMN to replicate the dramatic wrinkle prevention seen in this mouse study using specialised vesicle delivery. However, supporting overall cellular health through NAD+ restoration may contribute to healthier skin as one of many benefits.
Where This Research Goes Next
Human Trials Needed
Clinical trials in humans are essential to determine whether:
- NMN-loaded vesicles provide similar benefits in human skin
- The effects work on naturally aged skin (not just chemically accelerated ageing)
- Oral administration of vesicle-based formulations could work
- The approach is safe for long-term use
Oral Vesicle Delivery
Research is exploring whether people can orally ingest sEVs and absorb them effectively. If successful, this could enable NMN-loaded vesicle supplements that combine both approaches in a convenient form.
Systemic Effects
Since vesicles might stabilise NMN in circulation, future research should examine whether this approach benefits organs beyond skin, potentially slowing whole-body ageing processes.
Connecting the Dots: NAD+ and Ageing
This study demonstrates proof-of-concept that combining NMN with advanced delivery systems can enhance its effects on tissue ageing. The synergistic results - where the combination worked better than either approach alone - suggest NMN's benefits might be amplified through innovative delivery methods.
However, translating this to practical human applications requires significant additional research. For now, it represents an interesting research direction rather than an immediately available therapy.
Takeaways for Supplement Users
Evidence for NAD+ and Skin
This study adds to growing evidence that NAD+ levels matter for skin health and that restoring them through NMN may provide protective benefits.
Oral Supplementation Context
Whilst this study used specialised delivery methods unavailable to consumers, oral NMN supplementation still supports systemic NAD+ levels, which may benefit skin alongside numerous other tissues.
Part of Comprehensive Skin Care
Supporting skin health requires a multi-faceted approach:
- Sun protection (the single most important factor)
- Adequate hydration
- Nutrient-dense diet
- Quality sleep
- Not smoking
- NAD+ support through supplementation
NMN supplementation represents one component of this comprehensive approach, supporting cellular health from the inside out.
Our NMN Supplement
Pharmaceutical-grade NMN providing 500mg per capsule for systemic NAD+ support. Benefits throughout the body including:
- Cellular energy metabolism
- DNA repair processes
- Mitochondrial function
- Cellular stress resistance
- Overall healthy ageing support
Why Choose Our NMN:
- Manufactured to pharmaceutical standards in GMP-certified UK facilities
- Rigorous purity and quality testing
- Research-supported dosage
- Optimal bioavailability
- No unnecessary additives
The Bottom Line
This innovative study demonstrates that combining NMN with stem cell-derived vesicles delivered via microneedles dramatically reduced skin wrinkling, thinning, and cellular damage in a mouse model of accelerated skin ageing. The combination worked significantly better than either approach alone, suggesting synergistic effects.
However, several important caveats apply. The study used artificial ageing in mice, specialised vesicle delivery systems, and microneedle application - all quite different from taking oral NMN supplements. Human trials with naturally aged skin are needed to confirm whether similar benefits occur in people.
For those interested in supporting skin health, this research adds to evidence that NAD+ restoration through NMN may benefit skin tissue. Whilst oral supplements won't replicate the dramatic results seen with this specialised delivery system, supporting systemic NAD+ levels through regular supplementation represents a practical, evidence-based approach to maintaining cellular health as you age - with potential benefits for skin alongside numerous other tissues.
The study also highlights an exciting future direction: as research advances in vesicle-based oral delivery systems, we may eventually see consumer products that combine NMN with protective vesicles, potentially enhancing efficacy beyond current supplementation approaches.
Reference: Sun Z, et al. (2025). "Small extracellular vesicles derived from mesenchymal stromal cells loaded with β-nicotinamide mononucleotide activate NAD+/SIRT3 signaling pathway-mediated mitochondrial autophagy to delay skin aging." Stem Cell Research and Therapy, 16(1), 339.
These statements have not been evaluated by the Medicines and Healthcare products Regulatory Agency (MHRA). These products are not intended to diagnose, treat, cure or prevent any disease. This article discusses preliminary research and is not medical advice. Results from mouse studies using specialised delivery methods do not directly translate to oral NMN supplementation in humans.