Highlights

  • NMN injections more than doubled saliva secretions in old mice.
  • Injections reduced the protein abundance associated with age-related, dysfunctional senescent cells in salivary glands.
  • NMN treatments boosted gene activation for a water channel involved in saliva secretion called aquaporin5 (AQP5) to counteract an age-related dry mouth.

Saliva secretions are essential for cleaning the mouth, digestion, and fighting bacteria to maintain oral hygiene. Unfortunately, saliva flow from salivary glands, like the submandibular gland, can decrease with age or by taking certain medications. A loss of salivary flow can inhibit the protective functions of adequate saliva and increase the risk of dental cavities (known as caries). People can take prescription medications to stimulate saliva production, but researchers are still investigating why dry mouth worsens with age and are exploring new treatments.

Now, published in Biogerontology, Nagata and colleagues from Meiji Holdings Company in Japan show that nicotinamide mononucleotide (NMN) injections more than double salivary secretions in old mice. Furthermore, NMN reduces the abundance of proteins associated with senescent cells in submandibular salivary glands. NMN treatments also boost the activation of genes for a water channel with crucial roles in saliva secretions called AQP5. As we age, saliva secretions diminish, increasing the risk of dry mouth and tooth decay. The fundings from this study suggest NMN works against dry mouth in mice. These findings could help develop treatments for older adults to prevent dry mouth-associated issues like tooth cavities.

NMN More than Doubles Saliva Secretions in Old Mice

To find whether NMN treatment increases salivation in aged mice, Nagata and colleagues injected the mice with NMN once every two days for four weeks. Compared to young mice, untreated old mice displayed less than half the oral salivation. However, NMN treatment more than doubled salivation in old mice, comparable to levels seen in young mice. These findings suggest that NMN treatment restores salivation in old mice, providing a way to mitigate age-associated dry mouth.

NMN restores salivation against age-related dry mouth in old mice.
(Wakabayashi et al., 2024 | Biogerontology) NMN restores salivation against age-related dry mouth in old mice. Compared to young mice (YC), untreated old mice (OC) exhibited less than half the salivation as measured with salivary flow rate from the submandibular gland. Treating old mice with NMN (ON), however, nearly restored salivation to levels seen in young mice.

Since senescent cells may contribute to salivary gland aging and overall gland dysfunction, the Japanese researchers measured NMN’s effects on senescent cell abundance. As expected, untreated, old mice showed significantly elevated proteins associated with senescence (SA-β-gal) in submandibular glands. NMN treatment, however, trended toward lowering SA-β-gal levels, suggesting that NMN may diminish the abundance of senescent cells. Furthermore, since senescent cells release inflammatory factors into surrounding tissue, their presence could increase inflammation and drive tissue dysfunction, so reducing them may help explain increased salivary gland function with NMN.

Next, to get a better idea of how NMN increases salivation in old mice, Nagata and colleagues measured gene activity associated with AQP5 water channels in submandibular glands. They found that NMN treatment restored gene expression for AQP5 channels in old mice, comparable to levels seen in young mice. These results suggest that by reducing age-related senescent cell buildup and subsequent inflammation in the submandibular gland, AQP5 channels were restored, and salivation improved.

NMN restores gene expression for a water channel with crucial roles in salivation, AQP5, in old mice.
(Wakabayashi et al., 2024 | Biogerontology) NMN restores gene expression for a water channel with crucial roles in salivation—AQP5—in old mice. Compared to young mice (YC), untreated old mice (OC) exhibited significantly less gene expression for AQP5. Treating old mice with NMN (ON), however, nearly restored AQP5 gene expression to that seen in young mice.

Determining Whether NMN Fights a Dry Mouth in Aged Adults

Other data from the study showed that nicotinamide adenine dinucleotide (NAD+) levels fall in cells of the submandibular gland in old mice and that NMN restores NAD+. For this reason, it seems plausible that the mechanism underpinning an age-related dry mouth involves lower NAD+ levels. In that sense, restoring NAD with its NMN precursor could work to reduce senescent cells, lower inflammation, increase AQP5 channel levels and thus, restore salivation.

Whether these findings translate to humans will require human trials for confirmation. If we can simply restore salivation by boosting NAD+ in salivary glands with NAD+ precursors like NMN, such a treatment would serve as an easy fix for preventing oral decay as people age.