ArticleInternational journal of molecular medicine2020
Metformin attenuates the D‑galactose‑induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways.
Article in International journal of molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- Metformin alleviates presbycusis by activating the SIRT1/PINK1/GPX4 pathway in vitro and in vivo.Inflammopharmacology · 2026Article
- Multi-omics reveals mechanism of Qi-Po-Sheng-Mai granule in reducing atrial fibrillation susceptibility in aged rats.Chinese medicine · 2025Article
- Antitumor Effects of Metformin in Squamous Cell Carcinoma under Leptin Treatment Conditions.Preventive nutrition and food science · 2025Article
- Targeting the SYVN1-EGFR axis: a breakthrough strategy for TKI-resistant NSCLC.Cell death & disease · 2025Article
- Immunosenescence: signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- 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
- Polygenic Risk Score Modifies the Association of HbA1c With Hearing Loss in Middle-Aged and Older Chinese Individuals: The Dongfeng-Tongji Cohort.Diabetes care · 2024Article
- Underlying Mechanisms and Treatment of Cellular Senescence-Induced Biological Barrier Interruption and Related Diseases.Aging and disease · 2024Review
- Single-cell transcriptomic atlas of mouse cochlear aging.Protein & cell · 2023Article
- Epigenetic regulation of aging: implications for interventions of aging and diseases.Signal transduction and targeted therapy · 2022Review
- AAV-ie-mediated UCP2 overexpression accelerates inner hair cell loss during aging in vivo.Molecular medicine (Cambridge, Mass.) · 2022Article
- Article
- Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions.Aging and disease · 2022Article
- Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.Diabetes & metabolism · 2022Review
- Geroscience-guided repurposing of FDA-approved drugs to target aging: A proposed process and prioritization.Aging cell · 2022Review
- Metformin protects lens epithelial cells against senescence in a naturally aged mouse model.Cell death discovery · 2022Article
- Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms.Theranostics · 2022Review
- Icariin improves brain function decline in aging rats by enhancing neuronal autophagy through the AMPK/mTOR/ULK1 pathway.Pharmaceutical biology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age‑related hearing loss, also termed central presbycusis, is a progressive neurodegenerative disease; it is a devastating disorder that severely affects the quality of life of elderly individuals. Substantial evidence has indicated that oxidative stress and associated protein folding dysfunction have a marked influence on neurodegenerative diseases. In this study, we aimed to cells to investigate whether metformin protects against age‑related pathologies and to elucidate the underlying mechanisms; specifically, we focused on the role of unfolded protein response (UPR) via the AMPK/ERK1/2 signaling pathways. For this purpose, the biguanide compound, metformin, a medication widely used in the treatment of type 2 diabetes, was administered to rats in a model of mimetic aging. In addition, senescent PC12 were treated with metformin. Although it has been well established that UPR signaling is activated in response to cellular stress and is associated with the pathogenesis of neuronal deterioration, the detailed functions of the UPR in the auditory cortex remain unclear. We found that metformin treatment markedly affected the UPR and the AMPK/ERK1/2 signaling pathway, and maintained the auditory brainstem response (ABR) threshold during the aging process. The results indicated that the regulation of the UPR and AMPK/ERK1/2 signaling pathway by metformin significantly attenuated hearing loss, cell apoptosis and age‑related neurodegeneration. Reversing these harmful effects through the use of metformin suggests its involvement in restoring the antioxidant status and protein homeostasis related to the underlying pathology of presbycusis. The findings of this study may provide a better approach for the treatment of age‑related neurodegeneration diseases.
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