{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:18:16Z","timestamp":1787811496193,"version":"build-2784847793"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Approximately one in three adults aged 65\u201374 years reports hearing difficulty, including age-related hearing loss (AHL, presbycusis). The C57BL\/6 mouse is widely used in preclinical AHL research because it develops AHL relatively early. Calorie restriction (CR) attenuates AHL and improves healthspan and longevity in this strain. A recently developed transgenic C57BL\/6 mouse expressing naked mole-rat hyaluronan synthase 2 (\n                      <jats:italic>nmrHas2<\/jats:italic>\n                      ), which produces very high molecular mass hyaluronan (vHMM-HA), also exhibits improved healthspan, reduced inflammaging, and increased longevity. Therefore, we evaluated\n                      <jats:italic>nmrHas2<\/jats:italic>\n                      mice for evidence of alleviated AHL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To determine whether AHL is attenuated in\n                      <jats:italic>nmrHas2 mice<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study supplemented a larger investigation of\n                      <jats:italic>nmrHas2<\/jats:italic>\n                      and female reproductive aging. Tamoxifen administered at 1 month induced ubiquitous\n                      <jats:italic>nmrHas2<\/jats:italic>\n                      expression in\n                      <jats:italic>nmrHas2+<\/jats:italic>\n                      females;\n                      <jats:italic>nmrHas2\u2212<\/jats:italic>\n                      controls received tamoxifen or vehicle. Auditory brainstem response (ABR) testing was performed approximately 2 weeks before mice reached 3 or 12 months of age. Cochleae and reproductive tissues were collected following euthanasia approximately 2 weeks later.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ABR thresholds to clicks and six tones (4\u201332\u00a0kHz) showed marked hearing loss from 3 to 12 months of age in both\n                      <jats:italic>nmrHas2+<\/jats:italic>\n                      mice and controls, with no evidence that\n                      <jats:italic>nmrHas2<\/jats:italic>\n                      attenuated AHL. Cochlear\n                      <jats:italic>nmrHas2<\/jats:italic>\n                      expression in\n                      <jats:italic>nmrHas2+<\/jats:italic>\n                      mice was confirmed by quantitative RT-PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Ubiquitous\n                      <jats:italic>nmrHas2<\/jats:italic>\n                      expression did not attenuate AHL in C57BL\/6 mice despite previously reported benefits for other aging phenotypes. These findings contrast with CR, suggesting that vHMM-HA and CR influence aging through distinct mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fragi.2026.1936677","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:34:25Z","timestamp":1787808865000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-related hearing loss persisted in mice that had demonstrated improved healthspan, reduced inflammaging and extended lifespan following expression of the naked mole-rat transgene for hyaluronan synthase 2"],"prefix":"10.3389","volume":"7","author":[{"given":"Connor E.","family":"Owens","sequence":"first","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Cornell University, College of Veterinary Medicine","place":["Ithaca, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiden J.","family":"Borruso","sequence":"additional","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Cornell University, College of Veterinary Medicine","place":["Ithaca, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Place","sequence":"additional","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Cornell University, College of Veterinary Medicine","place":["Ithaca, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Seluanov","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rochester","place":["Rochester, NY, United States"]},{"name":"Department of Medicine, University of Rochester Medical Center","place":["Rochester, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Gorbunova","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rochester","place":["Rochester, NY, United States"]},{"name":"Department of Medicine, University of Rochester Medical Center","place":["Rochester, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Rochester School of Medicine and Dentistry","place":["Rochester, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ned J.","family":"Place","sequence":"additional","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences, Cornell University, College of Veterinary Medicine","place":["Ithaca, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s00360-007-0237-5","article-title":"Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species","volume":"178","author":"Buffenstein","year":"2008","journal-title":"J. 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