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NMN and intestinal bacteria, L. fermentum, remove active oxygen.

It has been proven to protect the skin of mice from harmful ultraviolet rays.

A common cause of skin aging

A major cause of skin aging is ultraviolet rays. Repeated exposure to sunlight or artificial UV rays (Ultraviolet rays) causes skin to age due to inflammation and oxidative stress . Oxidative stress increases the level of reactive oxygen species in the skin, which attack biological tissues and damage cells. In particular, it oxidizes collagen, which makes skin older. As inflammation levels increase, related factors secreted by inflammatory cells (such as TNF-α, tumor necrosis factor) also increase, accelerating the aging process in our bodies.

* Ultraviolet rays (UV): Light that has a significant effect on human skin as it is an electromagnetic wave with a wavelength range from 10 nm to 400 nm.

* Free radical: A general term for oxygen that is more unstable and reactive than ordinary oxygen, damaging cells, preventing regeneration, and accelerating aging.

Anti-aging properties of NMN and L. fermentum

Recent studies have shown a connection between the skin and the gut. Studies have shown that gut bacterial composition can regulate skin inflammation, and that skin exposure to UV rays alters gut bacterial composition.

One of the most common bacteria that affects the skin is Lactobacillus fermentum . L. fermentum has been shown to balance the composition of the gut microbiome. Studies have also shown that this gut bacterium can boost the immune system, lower cholesterol levels, and eliminate free radicals that cause oxidative stress.

* Microbiome: A collection of various microorganisms, including bacteria and viruses, living in the human body.

Another antioxidant and anti-inflammatory compound, NMN (Nicotinamide mononucleotide), increases levels of NAD+ (Nicotinamide adenine dinucleotide), a molecule that supports energy production and cellular health. Numerous studies have shown that taking NMN reduces free radicals and inflammation in the organs, and also offers anti-aging benefits.

Numerous studies have reported that both L. fermentum and NMN have protective effects against UV-damaged skin. The researchers decided to test the protective effects of L. fermentum and NMN on UV-damaged skin, and furthermore, to test the synergistic effects of L. fermentum and NMN.

Antioxidant capacity (absorbs free radicals)

To test its antioxidant potential , we mixed NMN and the contents of L. fermentum in a test tube with reactive oxygen species and measured the reactive oxygen species absorption capacity of NMN and intestinal bacteria.

Graph A. Absorption of reactive oxygen species OH by NMN, L. fermentum, mixture, and vitamin C (%)

Graph B. NMN, Absorption of reactive oxygen species ABTS by L. fermentum, mixture, and vitamin C (%) 

Graph C. DPPH absorption rate of NMN, L. fermentum, mixture, and vitamin C (%)

Graph D. Total concentration of reactive oxygen species absorbed by NMN, L. fermentum, mixture, and vitamin C (mM)

Graphs A, B, and C show how well NMN, L. fermentum , a mixture of NMN and L. fermentum , and vitamin C absorb three different reactive oxygen species: OH, ABTS, and DPPH. Graph D shows the total concentration of reactive oxygen species absorbed by NMN, L. fermentum , the mixture, and vitamin C.

The combination of NMN and L. fermentum demonstrated the best absorption of all three free radicals. Consequently, combining NMN with gut bacteria resulted in better free radical absorption than NMN or bacteria alone. The combination of NMN and L. fermentum also outperformed vitamin C, a well-known free radical scavenger.

Having tested the oxygen radical scavenging capabilities of NMN and L. fermentum , we now proceeded with research on the skin protection and health benefits of NMN and intestinal bacteria.

Improved skin protection function

The researchers transferred their previously in vitro experiments to live animals (in vivo) to see whether reducing reactive oxygen species using NMN or bacteria could protect mouse skin tissue after two weeks of UV exposure .

1) Skin dermis thickness

Figure A. Cross-section of skin after H&E staining (magnification x40)

Graph D. Skin dermis thickness ( µm)

* H&E staining: A staining method used when analyzing tissues. 

In Figure A, the arrow points to the dermal layer of the mouse skin. In Figure A, the Normal group is the group that was not exposed to UVB (Ultraviolet B), while the Model group is the group that was exposed to UV for two weeks and then did not undergo any treatment.

* Dermis: A thick layer of cells containing blood vessels just below the epidermis, making up 90% of the skin.

* UVB: Ultraviolet rays with a wavelength of 290-320 mm

When normal mouse skin tissue is exposed to ultraviolet rays, the dermis becomes thinner. When NMN, L. fermentum , and vitamin C were administered to the model group with thinned skin, the dermis was confirmed to thicken again. The group administered NMN, L. fermentum (NMN, L) showed sufficient dermis recovery effect on its own, but the mice administered a combination of the two substances (NMN+L) showed skin tissue preservation similar to the normal group compared to the mice administered each substance separately. Microscopic examination of the skin revealed that the combination of NMN and L. fermentum significantly protected the skin from ultraviolet rays .

2) Skin collagen fiber structure

Figure B. Cross-section of skin after Masson staining (magnification x40)  

* Masson staining: A staining method used to detect specific components such as collagen fibers. Collagen fibers are stained blue, muscle fibers are stained red, and nuclei are stained black.

In Figure B, arrows point to collagen fibers stained blue.

* Collagen fibers: Fibrous proteins that form a network in the dermal layer of the skin, supporting and connecting cells and acting as a framework.

When normal rat skin tissue is exposed to ultraviolet rays, the number of collagen fiber bundles is significantly reduced and the collagen fibers are damaged, resulting in an incomplete structure. When NMN, L. fermentum , and vitamin C (NMN, L, VC) were administered to the model group, a smaller number of collagen fibers was observed than in the normal group, but a larger number than in the model group. The combination of NMN and L. fermentum (NMN+L) increased the number more than NMN, L. fermentum , and vitamin C, respectively. It was found that the combination of NMN and L. fermentum increased the number of collagen fibers that had been reduced by exposure to ultraviolet rays .

3) Degree of inflammation according to the number of mast cells in the skin

Figure C. Cross-section of skin after toluidine blue staining (magnification x40)

Graph E. Number of mast cells

* Toluidine blue staining: A staining method used to detect granules in the cytoplasm of mast cells.

In Figure C, the arrow points to mast cells , which are stained as small blue dots. Exposure of the skin to UVB induces the production of skin mast cells, which leads to skin inflammation.

* Mast cells: inflammatory cells that play an important role in the development of asthma and allergic diseases, and are also used as an indicator of inflammation.

After UVB radiation exposure, the number of mast cells in the dermis increased fourfold compared to the normal group . When NMN and L. fermentum were simultaneously supplemented (NMN+L) in the model group, the number of mast cells increased only about twice that of the normal group. Therefore, it was found that the combination treatment showed a better protective effect than NMN or bacteria alone .

The combination of NMN and L. fermentum demonstrated superior oxygen radical absorption capacity compared to other substances. Furthermore, the oxygen radical-reducing properties of NMN and L. fermentum led to protection of skin tissue damaged by UV rays and a reduction in mast cell proliferation. This demonstrated that NMN and L. fermentum treatment can protect the skin and prevent aging .

[References and Figure Source]

[1] Intestinal Bacterium and NMN Synergistically Enhance Skin Protection

https://www.nmn.com/news/intestinal-bacterium-nmn-enhance-skin-protection

[2] Nicotinamide Mononucleotide Combined With Lactobacillus fermentum TKSN041 Reduces the Photoaging Damage in Murine Skin by Activating AMPK Signaling Pathway

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.643089/full

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