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Could α-Klotho Unlock the Key Between Depression and Dementia in the Elderly: from Animal to Human Studies

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Abstract

α-Klotho is known for its aging-related functions and is associated with neurodegenerative diseases, accelerated aging, premature morbidity, and mortality. Recent literature suggests that α-Klotho is also involved in the regulation of mental functions, such as cognition and psychosis. While most of studies of α-Klotho are focusing on its anti-aging functions and protective role in dementia, increasing evidence showed many shared symptoms between depression and dementia, while depression has been proposed as the preclinical stage of dementia such as Alzheimer’s disease (AD). To see whether and how α-Klotho can be a key biological link between depression and dementia, in this review, we first gathered the evidence on biological distribution and function of α-Klotho in psychiatric functions from animal studies to human clinical investigations with a focus on the regulation of cognition and mood. Then, we discussed and highlighted the potential common underlying mechanisms of α-Klotho between psychiatric diseases and cognitive impairment. Finally, we hypothesized that α-Klotho might serve as a neurobiological link between depression and dementia through the regulation of oxidative stress and inflammation.

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Funding

This work was supported by the National Natural Science Foundational of China [#9184910028 for RL].

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  1. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, 100069, China

    Xiang Gao, Yuhong Li, Guangwei Ma, Qi Deng, Claire X. Zhang & Rena Li

  2. Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Beijing, 100088, China

    Zuoli Sun, Hong Xu & Rena Li

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  1. Xiang Gao
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XG and RL conceived and wrote the article. CXZ, YL, ZS, HX, GM, and QD critically reviewed the manuscript.

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Gao, X., Li, Y., Sun, Z. et al. Could α-Klotho Unlock the Key Between Depression and Dementia in the Elderly: from Animal to Human Studies. Mol Neurobiol 58, 2874–2885 (2021). https://doi.org/10.1007/s12035-021-02313-0

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