{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T06:24:01Z","timestamp":1793773441099,"version":"4.6.1"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Age\u2010related 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\u2010term use and is already shown effective in various disease models including Alzheimer's and Parkinson's disease. It has also been beneficial against noise\u2010induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild\u2010type mouse strains, we show that long\u2010term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age\u2010associated 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.<\/jats:p>","DOI":"10.1111\/acel.13909","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T06:36:57Z","timestamp":1688366217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Long\u2010term\n                    <scp>NAD<\/scp>\n                    + supplementation prevents the progression of age\u2010related hearing loss in mice"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5724-061X","authenticated-orcid":false,"given":"Mustafa N.","family":"Okur","sequence":"first","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcin Duan","family":"Sahbaz","sequence":"additional","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risako","family":"Kimura","sequence":"additional","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Manor","sequence":"additional","affiliation":[{"name":"Waitt Advanced Biophotonics Center Salk Institute for Biological Studies  La\u00a0Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimin","family":"Patel","sequence":"additional","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Hyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Andrade","sequence":"additional","affiliation":[{"name":"Waitt Advanced Biophotonics Center Salk Institute for Biological Studies  La\u00a0Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrakala","family":"Puligilla","sequence":"additional","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6094-4084","authenticated-orcid":false,"given":"Deborah L.","family":"Croteau","sequence":"additional","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"},{"name":"Computational Biology &amp; Genomics Core, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-6429","authenticated-orcid":false,"given":"Vilhelm A.","family":"Bohr","sequence":"additional","affiliation":[{"name":"Section on DNA Repair, National Institute on Aging National Institutes of Health  Baltimore Maryland USA"},{"name":"Danish Center for Healthy Aging University of Copenhagen  Copenhagen N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00282"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.09.020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201694914"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019194"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2018.11.009"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.11.003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0389-10.2010"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.04.022"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00313-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.026099"},{"issue":"10","key":"e_1_2_9_12_1","first-page":"1","article-title":"NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome","volume":"101","author":"Fang E. 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