Growth hormone-releaser diet attenuates cognitive dysfunction in klotho mutant mice via insulin-like growth factor-1 receptor activation in a genetic aging model

Seok Joo Park, Yoon Hee Chung, Jeong Hyun Lee, Duy Khanh Dang, Yunsung Nam, Ji Hoon Jeong, Yong Sun Kim, Toshitaka Nabeshima, Eun Joo Shin, Hyoung Chun Kim

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background: It has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH)/insulin-like growth factor-1 (IGF-1). Methods: In this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice. Results: The GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt)/phospho- glycogen synthase kinase3β (p-GSK3β), phospho-extracellular signal-related kinase (p-ERK), and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK), Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist. Conclusion: The results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

Original languageEnglish
Pages (from-to)336-348
Number of pages13
JournalEndocrinology and Metabolism
Volume29
Issue number3
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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