The study, published in Cell Metabolism, identifies a way to prevent noise-induced hearing loss in a mouse using a simple chemical compound that is a precursor to vitamin B3.
Led by Kevin Brown from the University of North Carolina School of Medicine, the team nicotinamide riboside (NR) to protect the nerves that supply the cochlea - which transmits sound information through these nerves to the brain. The use of NR prevented damage to the nerves, which can be caused by exposure to loud noises.
The team set about trying to prevent this nerve damage by giving mice NR (a vitamin B3 precursor) before or after exposing them to loud noises. - finding that NR was successful at preventing damage to the synaptic connections, avoiding both short-term and long-term hearing loss. What's more, NR was equally effective regardless of whether it was given before or after the noise exposure, said the team.
Brown and his colleagues said the discovery has important implications not only for preventing hearing loss, but also potentially for reversing some aging-related conditions that are linked to the same protein.
"One of the major limitations in managing disorders of the inner ear, including hearing loss, is there are a very limited number of treatments options," explained the lead author - who conducted the research while at Weill Cornell. "This discovery identifies a unique pathway."
NR potential
The team chose NR because it is a precursor to the chemical compound nicotinamide adenine dinucleotide (NAD+), which had previously been shown by Brown and his colleagues to protect cochlea nerve cells from injury. However, they noted that NAD+ is an unstable compound, calling into question whether it could be used out of the petri-dish and in a live animal. As such, attention was turned to the vitamin B3 precursor.
"NR gets into cells very readily and can be absorbed when you take it orally," noted Professor Jaffrey of Weill Cornell.
Anti-aging potential?
Beyond just preventing hearing loss, the researchers think that the underlying way NR protects nerve cells may have broader applications. Indeed, the team showed that NR and NAD+ prevent hearing loss by increasing the activity of the protein sirtuin 3 (SIRT3), which is critically involved in the function of mitochondria. They suggested that it was this enhancement of SIRT3 that was behind the protective properties of NR.
To test this, Brown and his colleagues manipulated SIRT3 levels independently of NR to see if they could still prevent noise-induced hearing loss by administering NR. In these experiments, deleting the SIRT3 gene in mice abolished any of the protective properties of NR.
The researchers also showed that a new strain of mice engineered to express high levels of SIRT3, were inherently resistant to noise-induced hearing loss, even without administration of NR.
The team noted that SIRT3 decreases naturally as we age, which could partially explain aging-related hearing loss. Additionally, some individuals carry different versions of the SIRT3 genes that result in reduced enzyme activity, which may make them more susceptible to noise-induced hearing loss, they said.
"The success of this study suggests that targeting SIRT3 using NR could be a viable target for treating all sorts of aging-related disorders -not only hearing loss but also metabolic syndromes like obesity, pulmonary hypertension, and even diabetes," said Professor Verdin from the University of California, San Francisco.