Cellular energy route finding may improve understanding of aging, chronic disease

By Tauren Dyson

Jan. 7 (UPI) -- Scientists have found a cellular route for energy that could shed more light on how humans age and develop chronic diseases.

Researchers from the Washington University of St. Louis have uncovered a once unknown path for nicotinamide mononucleotide, or NMN, which helps fuel the human body, according to a new study published Monday in Nature Metabolism.


"To achieve such fast uptake of NMN into the tissues, we speculated that there must be a specific NMN transporter that moves NMN directly into cells, even though no one had ever seen such a thing," Shin-ichiro Imai, a professor of developmental biology at Washington University, said in a news release.

For this protein highway, the researchers found that cells must create a molecular transport system. First, NMN provides energy to nicotinamide adenine dinucleotide, or NAD, a key molecule that also helps fuel the body. When people age, they lose NAD, causing the body to lose energy and function.

To transport fuel, NMN needs a transporter protein called Slc12a8, which requires sodium ions to make the delivery. Cells call on the Slc12a8 gene when NAD levels begin to lag.


The researchers tested the importance of Slc12a8 by purposely lowering NAD levels within test mice and injecting them with NMN to make up for the loss. Not only did NAD produce more NMN, it increased the amount of Slc12a8 to make way for more NMN. It's similar to how an expanded bridge can carry more cars.

The researchers concluded that it's not enough to provide more NMN to increase energy levels of older subjects, but to also improve the capability of Slc12a8.

In past work, Imai observed that more NMN enhanced metabolism throughout the bodies of lab mice, including better liver function, bone density, eye function, insulin sensitivity, immune function, body weight and activity levels.

"What may be important in a future strategy is the combination of giving NMN along with stimulating the transport of NMN into cells," Imai said. "With aging, we see a bottleneck in NAD production. The body loses its ability to manufacture NAD over time. At the same time, it seems to begin burning more NAD, likely due to chronic inflammation. If we can give NMN and aid its transport into cells, that may be a way to bypass the bottleneck."

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