Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice

Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice. Okur, M. N., Kimura, R., Sahbaz, B. D., Manor, U., Patel, J., Andrade, L., Puligilla, K., Croteau, D. L., & Bohr, V. A. bioRxiv, Cold Spring Harbor Laboratory, 2022.

Paper doi abstract bibtex

Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer\textquoterights and Parkinson\textquoterights Disease. It has also been beneficial against noise induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.Competing Interest StatementV Bohr received Nicotinamide riboside from Chromadex Corp

@article {Okur2022.08.25.505332,
	author = {Mustafa N. Okur and Risako Kimura and Burcin Duan Sahbaz and Uri Manor and Jaimin Patel and Leo Andrade and Kala Puligilla and Deborah L. Croteau and Vilhelm A. Bohr},
	title = {Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice},
	elocation-id = {2022.08.25.505332},
	year = {2022},
	doi = {10.1101/2022.08.25.505332},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Age-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer{\textquoteright}s and Parkinson{\textquoteright}s Disease. It has also been beneficial against noise induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.Competing Interest StatementV Bohr received Nicotinamide riboside from Chromadex Corp},
	URL = {https://www.biorxiv.org/content/early/2022/08/26/2022.08.25.505332},
	eprint = {https://www.biorxiv.org/content/early/2022/08/26/2022.08.25.505332.full.pdf},
	journal = {bioRxiv}
}

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