ArticleThe Journal of clinical investigation2018
Tuberous sclerosis complex-mediated mTORC1 overactivation promotes age-related hearing loss.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 88 citations in OpenAlex.
- Activating GPR55 protects cochlear hair cells against cisplatin-induced ototoxicity via inhibiting MAPK pathway.Scientific reports · 2026Article
- Superenhancer-mediated ferroptosis in age-related hearing loss: cochlear epigenomics.Cellular and molecular life sciences : CMLS · 2026Article
- Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?International journal of molecular sciences · 2026Review
- The mTOR Pathway in Hearing Disorders: Mechanistic Links to Aging, Regeneration, and Neurodegeneration.Molecular neurobiology · 2026Review
- Advances in the treatment of age-related hearing loss: from molecular mechanisms to targeted interventions.Frontiers in aging neuroscience · 2026Review
- HCMV immediate-early protein IE2 induces neurotoxicity and hearing loss by disrupting TSC2-mTOR signaling and metabolic homeostasis.Journal of neuroinflammation · 2025Article
- RONIN/HCF1-TFEB Axis Protects Against D-Galactose-Induced Cochlear Hair Cell Senescence Through Autophagy Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Presbycusis: Pathology, Signal Pathways, and Therapeutic Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Associations Between Occupational Noise Exposure, Aging, and Gender and Hearing Loss: A Cross-Sectional Study in China.Audiology research · 2025Article
- TNFAIP8L2 as a dual regulator of mTORC1 signaling: Implications for therapy in presbycusis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- TNFAIP8L2 maintains hair cell function and regulates age-related hearing loss via mTORC1 signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Review
- Kolliker's Organ and Its Functional Role in the Development of Corti's Organ and Auditory Systems.Audiology research · 2025Review
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- Phenotypic changes of auditory nerve fibers after excitotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Pathophysiological insights and therapeutic developments in age-related hearing loss: a narrative review.Frontiers in aging neuroscience · 2025Review
- The Role of Molecular and Cellular Aging Pathways on Age-Related Hearing Loss.International journal of molecular sciences · 2024Review
- A Low Dose of Rapamycin Promotes Hair Cell Differentiation by Enriching SOX2Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The underlying molecular mechanisms of age-related hearing loss (ARHL) in humans and many strains of mice have not been fully characterized. This common age-related disorder is assumed to be closely associated with oxidative stress. Here, we demonstrate that mTORC1 signaling is highly and specifically activated in the cochlear neurosensory epithelium (NSE) in aging mice, and rapamycin injection prevents ARHL. To further examine the specific role of mTORC1 signaling in ARHL, we generated murine models with NSE-specific deletions of Raptor or Tsc1, regulators of mTORC1 signaling. Raptor-cKO mice developed hearing loss considerably more slowly than WT littermates. Conversely, Tsc1 loss led to the early-onset death of cochlear hair cells and consequently accelerated hearing loss. Tsc1-cKO cochleae showed features of oxidative stress and impaired antioxidant defenses. Treatment with rapamycin and the antioxidant N-acetylcysteine rescued Tsc1-cKO hair cells from injury in vivo. In addition, we identified the peroxisome as the initial signaling organelle involved in the regulation of mTORC1 signaling in cochlear hair cells. In summary, our findings identify overactive mTORC1 signaling as one of the critical causes of ARHL and suggest that reduction of mTORC1 activity in cochlear hair cells may be a potential strategy to prevent ARHL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.