The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Activation of SIRT3 by the NAD(+) precursor nicotinamide riboside protects from noise-induced hearing loss
Open accessAbstract
Intense noise exposure causes hearing loss by inducing degeneration of spiral ganglia neurites that innervate cochlear hair cells. Nicotinamide adenine dinucleotide (NAD(+)) exhibits axon-protective effects in cultured neurons; however, its ability to block degeneration in vivo has been difficult to establish due to its poor cell permeability and serum instability. Here, we describe a strategy to increase cochlear NAD(+) levels in mice by administering nicotinamide riboside (NR), a recently described NAD(+) precursor. We find that administration of NR, even after noise exposure, prevents noise-induced hearing loss (NIHL) and spiral ganglia neurite degeneration. These effects are mediated by the NAD(+)-dependent mitochondrial sirtuin, SIRT3, since SIRT3-overexpressing mice are resistant to NIHL and SIRT3 deletion abrogates the protective effects of NR and expression of NAD(+) biosynthetic enzymes. These findings reveal that administration of NR activates a NAD(+)-SIRT3 pathway that reduces neurite degeneration caused by noise exposure.
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In the citing paper
“In neurons, SIRT3 mediates the adaptive responses of neurons to exercise, intermittent fasting, and excitatory challenges and helps prevent noise-induced hearing loss and spiral ganglia neurite degeneration (Brown et al., 2014; Cheng et al., 2016; Liu et al., 2019).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Brown et al., 2014
In the citing paper
“Overall, Wlds mouse studies largely show the neuro protective function of the biosynthetic enzymes NMNAT1, NMNAT2 and NMNAT3 (REFS142,150–152) and their protective role in several neurodegenerative disorders, including Parkinson disease153–155.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [155]
In the citing paper
“These effects appear to be mediated in the mitochondria because SIRT3-overexpressing mice are resistant to noise-induced hearing loss and SIRT3 deletion abrogates the protective effects of nicotinamide riboside ((Brown et al. 2014))”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Brown et al. 2014
In the citing paper
“Administering the NAD precursor nicotinamide riboside prevents noise-induced hearing loss and degeneration of spiral ganglia neurite degeneration.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Brown et al. 2014
In the citing paper
“SIRT3 also protects against hearing loss in response to intense noise exposure (Brown et al. 2014).”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Brown et al. 2014
In the citing paper
“These effects are dependent on SIRT3, since SIRT3-overexpressing mice are resistant to noise-induced hearing loss and SIRT3 deletion abrogates the protective effects of NR.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Brown et al. 2014
In the citing paper
“Cochlear NAD(+) levels increased in mice after administering nicotinamide riboside, a precursor to NAD(+) and prevented noise-induced hearing loss.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Brown et al. 2014
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Citations
Cites
Adding Insult to Injury: Cochlear Nerve Degeneration after “Temporary” Noise-Induced Hearing Loss
Kujawa, S. G., & Liberman, M. C. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2845-09.2009 · Cited by 2,475
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.022 · Cited by 1,238
Self-citationSomeya, S., Yu, W., Hallows, W. C., Xu, J., Vann, J. M., Leeuwenburgh, C., Tanokura, M., Denu, J. M., & Prolla, T. A. (2010) · Cell · doi:10.1016/j.cell.2010.10.002 · Cited by 1,150
Increased Nuclear NAD Biosynthesis and SIRT1 Activation Prevent Axonal Degeneration
Araki, T., Sasaki, Y., & Milbrandt, J. (2004) · Science · doi:10.1126/science.1098014 · Cited by 1,060
Hirschey, M. D., Shimazu, T., Jing, E., Grueter, C. A., Collins, A. M., Aouizerat, B., Stančáková, A., Goetzman, E., Lam, M. M., Schwer, B., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.019 · Cited by 787 · cited 1×
“Polymorphisms exist in the SIRT3 gene that affects its activity (Hirschey et al., 2011), and may in turn contribute to susceptibility to NIHL.”
Self-citationBieganowski, P., & Brenner, C. (2004) · Cell · doi:10.1016/s0092-8674(04)00416-7 · Cited by 750
Bogan, K. L., & Brenner, C. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155443 · Cited by 707
Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral Nerve
Lunn, E. R., Perry, V. H., Brown, M. C., Rosen, H., & Gordon, S. (1989) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1989.tb00771.x · Cited by 646
Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome
Hebert, A. S., Dittenhafer-Reed, K. E., Yu, W., Bailey, D. J., Selen, E. S., Boersma, M. D., Carson, J. J., Tonelli, M., Balloon, A. J., Higbee, A. J., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.10.024 · Cited by 636
Dynamics of Noise-Induced Cellular Injury and Repair in the Mouse Cochlea
Wang, Y., Hirose, K., & Liberman, M. C. (2002) · Journal of the Association for Research in Otolaryngology · doi:10.1007/s101620020028 · Cited by 560
Cited by
Sorted by citations
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648
NAD+ metabolism and its roles in cellular processes during ageing
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00313-x · Cited by 1,617
Self-citationNAD + in aging, metabolism, and neurodegeneration
Verdin, E. (2015) · Science · doi:10.1126/science.aac4854 · Cited by 1,319
Self-citationNAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
Yoshino, J., Baur, J. A., & Imai, S.-I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.11.002 · Cited by 1,061
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.09.013 · Cited by 930
Metadata
- Authors
- Brown, K. D., Maqsood, S., Huang, J.-Y., Pan, Y., Harkcom, W., Li, W., Sauve, A., Verdin, E., & Jaffrey, S. R.
- Affiliations
- Cornell University (US)
- Gladstone Institutes (US)
- Corresponding author
- Brown, Kevin D.
- Verdin, Eric
- Jaffrey, Samie R.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 20
- Issue
- 6
- Pages
- 1059-1068
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4940130
- OpenAlex
- W2044697772
- Cited by
- 277
- References
- 55
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 17 · 2023: 24 · 2022: 33 · 2021: 26 · 2020: 29 · 2019: 27 · 2018: 30 · 2017: 26 · 2016: 24 · 2015: 14 · 2014: 2
- FWCI
- 11.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- New York State Department of Health
- National Institutes of Health
- Weill Cornell Medical College
- National Cancer Institute (R21CA176638, CA176638)
- National Institute of Neurological Disorders and Stroke (NS56306, R01NS056306)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
- Health Sciences › Health Professions › Speech and Hearing › Hearing Loss and Rehabilitation
- Keywords
- noise-induced hearing loss, nicotinamide riboside, SIRT3, NAD+, spiral ganglion neurons, neurite degeneration, cochlear hair cells, mitochondrial sirtuins, NAD biosynthesis, axon protection, neuroprotection
- MeSH terms
- Animals, Female, Hearing Loss, Noise-Induced, Male, NAD, Niacinamide, Pyridinium Compounds, Mice, Sirtuin 3
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