Open Access

Metformin attenuates the D‑galactose‑induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways

  • Authors:
    • Hua Cai
    • Baoai Han
    • Yujuan Hu
    • Xueyan Zhao
    • Zuhong He
    • Xubo Chen
    • Haiying Sun
    • Jie Yuan
    • Yongqin Li
    • Xiuping Yang
    • Wen Kong
    • Wei‑Jia Kong
  • View Affiliations

  • Published online on: January 8, 2020     https://doi.org/10.3892/ijmm.2020.4453
  • Pages: 715-730
  • Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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March 2020
Volume 45 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Cai, H., Han, B., Hu, Y., Zhao, X., He, Z., Chen, X. ... Kong, W. (2020). Metformin attenuates the D‑galactose‑induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways. International Journal of Molecular Medicine, 45, 715-730. https://doi.org/10.3892/ijmm.2020.4453
MLA
Cai, H., Han, B., Hu, Y., Zhao, X., He, Z., Chen, X., Sun, H., Yuan, J., Li, Y., Yang, X., Kong, W., Kong, W."Metformin attenuates the D‑galactose‑induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways". International Journal of Molecular Medicine 45.3 (2020): 715-730.
Chicago
Cai, H., Han, B., Hu, Y., Zhao, X., He, Z., Chen, X., Sun, H., Yuan, J., Li, Y., Yang, X., Kong, W., Kong, W."Metformin attenuates the D‑galactose‑induced aging process via the UPR through the AMPK/ERK1/2 signaling pathways". International Journal of Molecular Medicine 45, no. 3 (2020): 715-730. https://doi.org/10.3892/ijmm.2020.4453