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Volume 49 Issue 4
Apr.  2022
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Article Navigation >  Journal of Genetics and Genomics  > 2022  >  49(4): 287-298

Mitochondrial sirtuins, metabolism, and aging

doi: 10.1016/j.jgg.2021.11.005
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    a State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;

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    b Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China;

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    c Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China;

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    d University of Chinese Academy of Sciences, Beijing 100049, China;

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    e State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;

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    f Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China

Funds:

This work was supported by the National Natural Science Foundation of China (91949209, 91749202, 92149301, 92168201), the National Key Research and Development Program of China (2018YFC2000100, 2020YFA0804000), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010000), the National Natural Science Foundation of China (81921006, 81625009, 82125011), the Key Research Program of the Chinese Academy of Sciences (KFZD-SW-221), the 14th Five-year Network Security and Informatization Plan of Chinese Academy of Sciences (WX145XQ07-18), Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301), and the Milky Way Research Foundation (MWRF).

  • Received Date: 2021-08-11
  • Revised Date: 2021-11-09
  • Accepted Date: 2021-11-10
  • Publish Date: 2022-04-30
    Abstract
  • Maintaining metabolic homeostasis is essential for cellular and organismal health throughout life. Multiple signaling pathways that regulate metabolism also play critical roles in aging, such as PI3K/AKT, mTOR, AMPK, and sirtuins (SIRTs). Among them, sirtuins are known as a protein family with versatile functions, such as metabolic control, epigenetic modification and lifespan extension. Therefore, by understanding how sirtuins regulate metabolic processes, we can start to understand how they slow down or accelerate biological aging from the perspectives of metabolic regulation. Here, we review the biology of SIRT3, SIRT4, and SIRT5, known as the mitochondrial sirtuins due to their localization in the mitochondrial matrix. First, we will discuss canonical pathways that regulate metabolism more broadly and how these are integrated with aging regulation. Then, we will summarize the current knowledge about functional differences between SIRT3, SIRT4, and SIRT5 in metabolic control and integration in signaling networks. Finally, we will discuss how mitochondrial sirtuins regulate processes associated with aging and aging-related diseases.
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