NMN Transporter Discovered: New Cellular Fuel Delivery Route for Anti-Aging & Disease Treatments

    You may try to control your weight, control what you eat and build daily routines to maintain a healthy lifestyle and a healthy look, but one thing you can’t control or change is the passing of time and your age.

    Shin-Ichiro Imai, PhD, a professor of developmental biology at Washington University School of Medicine in St. Louis, believes in finding ways for people to age better than ever. He calls it productive aging. Imai is using science to reveal avenues for older people to age in a way that’s healthier, having more energy and becoming more active. He’s motivated by the idea of humans having a metabolism of 10 to 20 years younger as they age.

    Studying basic mechanisms of aging and longevity, Imai had some breakthrough discoveries in his lab. Among the latest, identifying a previously unknown route for cellular fuel delivery. It’s a finding that could shed light on the process of aging and chronic diseases that accompany aging.

    Aging cells gradually lose their ability to take in and process fuel. By boosting the energy supply of aging cells, researchers hope to slow aging.

    It’s all related to Imai’s research on a chemical compound found naturally in our bodies and some produce we eat. The molecule is callednicotinamide mononucleotide (NMN). His work has shown how NMN boosts nicotinamide adenine dinucleotide (NAD), a key element of any cell’s fuel supply chain.

    “This compound, NAD, is required to maintain our energy and our metabolism,” explained Imai.

    Proven through Imai’s previous research, inactive older mice became active again when his lab gave them a premium oral NMN supplement manufactured for research. The scientists noticed how NMN gets into their blood stream very quickly when putting it in their drinking water.

    “It happens within five or 10 minutes,” said Imai. “NMN levels peak up around 10-15 minutes then goes down to the basic level, so it’s relatively very quick.”

    Because NMN speedily gets into the cells of tissues throughout the mouse body, the researchers suspected a specific molecule was providing a direct route to cells. Imai’s lab launched new research to name the mystery transporter that’s providing fuel delivery to cells in hopes it could be activated to further improve the performance of NMN.

    Staff scientistAlessia Grozio, PhD, led the study proving the Slc12a8 protein is the transporter they suspected.

    “We discovered that this gene, Slc12a8, is expressed everywhere and in every tissue, in mice at least, “ said Grozio.

    Grozio further showed that cells dial up the expression of the Slc12a8 gene when NAD levels fall. This means cells don’t passively accept loss of NAD. Grozio said cells work to maintain their fuel supply by increasing the amounts of Slc12a8 to increase their capacity to bring the raw materials (NMN) into the cell, which is required to make NAD.  Therefore, aging cells are able to compensate for a depleted fuel supply. Grozio tracked part of the process that indicates how cells will make more NMN transporters when NAD levels fall, increasing the amount of NMN they bring inside.

    For the anti-aging benefits of increasing NMN, Imai said the discovery will prove invaluable to the future efficacy of NMN nutraceuticals, or even finding a way to increase the uptake of the NMN our bodies naturally produce.

    “An NMN transporter-activator could be a really interesting drug,” Imai said.

    Pertaining to the future of clinically proven NMN nutraceuticals, Imai said a lower dose of NMN would be needed with the creation of a drug designed to activate the transporter. Having the ability to reach the cells efficiently would require a lower dose. According to Imai, a drug activating Slc12a8 would minimize any possible negative effects of high doses of NMN nutraceuticals. He hopes drugs activating the NMN transporter can slow aging and age-related diseases in people.

    Imai explained how activating the transporter could also benefit treatment of other diseases, as scientists elsewhere have discovered connections with slc12a8. One example is pancreatic cancer. Imai said he hopes this transporter can be activated for drug therapies treating diseases in specific organs and tissues.

    With this in mind, Imai’s lab already has identified small molecules that enhance the function of the NMN transporter. Working with Washington University’s Office of Technology Management, this technology has been licensed to a company in Japan called Teijin Limited that is working on new therapies targeting the chronic diseases of aging. Imai’s lab is also conducting an ongoing clinical trial at the School of Medicine investigating the effects of giving older adults 250mg daily of a specific NMN nutraceutical.