Using a supplement that is a source of Vitamin B3, scientists have successfully prevented noise-induced hearing loss in mice. These promising results suggest that in the future, it may be possible to treat the same condition in humans using this compound. The work has been published in Cell Metabolism.

Our delicate ears are very sensitive and can be damaged by a variety of things, such as noise, trauma and certain diseases, which can all cause us to lose our hearing. Intense noises, for example, can induce hearing loss by triggering the degeneration of the nerve cells, or neurons, that are connected to the tiny hair cells of the cochlea.

The cochlea is a fluid-filled, spiral-shaped cavity of the inner ear that looks like a snail shell. It is the job of the microscopic hair cells within the cochlea to translate vibrations caused by sound waves into electrical impulses that are carried to the brain by a bundle of neurons called the spiral ganglion.

Since it is known that damage to the delicate nerve endings which lead to the spiral ganglion is what ultimately leads to noise-induced hearing loss, scientists from Weill Cornell Medical College and the Gladstone Institutes wondered whether it might be possible to somehow protect them from harm.

They started off by contemplating the possibility of using a molecule called NAD⁺ which has been shown to exert protective effects to neurons in cell culture. However, this molecule is unfortunately unstable and difficult to get inside cells, meaning that successfully administering it to animals is difficult. The researchers therefore wondered whether it might be possible to increase NAD⁺ levels in the cochlea using a different strategy, so they turned to a molecule called nicotinamide riboside (NR).

NR, which is found in trace amounts in certain foods, is a precursor of NAD and also a source of Vitamin B3. Furthermore, NR enters cells easily and is quickly absorbed when administered orally, meaning it is an ideal drug candidate.

To investigate whether NR could prevent nerve damage in the cochlea, the team administered the compound to mice both before and after exposing them to loud noises. They found that NR successfully protected the nerve endings, avoiding both short-term and long-term hearing loss. Furthermore, they found it to be equally effective whether it was administered before or after noise exposure.

The researchers also took this one step further by identifying the pathway by which NR prevents nerve damage. They found that NR increases the activity of an NAD⁺-dependent molecule called sirtuin 3 (SIRT3), which is known to play vital roles in maintaining the function of mitochondria—the sausage-shaped powerhouses of cells.

When they engineered the mice to express high levels of SIRT3, the animals were resistant to noise-induced hearing loss (NIHL). Furthermore, when they deleted the SIRT3 gene, NR no longer protected the mice from NIHL.  

SIRT3 levels are known to naturally deplete as we age, which could be a contributing factor to age-related hearing loss. The researchers therefore believe that targeting SIRT3 using NR could possibly open up new treatment avenues for age-related hearing loss, and possibly even some other age-related disorders.

[Via Weill Cornell and Cell Metabolism]