Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans

  1. Yanan Sun
  2. Meijiao Li
  3. Dongfeng Zhao
  4. Xin Li
  5. Chonglin Yang
  6. Xiaochen Wang  Is a corresponding author
  1. Institute of Biophysics Chinese Academy of Sciences, China
  2. Yunnan University, China

Abstract

Lysosomes play important roles in cellular degradation to maintain cell homeostasis. In order to understand whether and how lysosomes alter with age and contribute to lifespan regulation, we characterized multiple properties of lysosomes during the aging process in C. elegans. We uncovered age-dependent alterations in lysosomal morphology, motility, acidity and degradation activity, all of which indicate a decline in lysosome function with age. The age-associated lysosomal changes are suppressed in the long-lived mutants daf-2, eat-2 and isp-1, which extend lifespan by inhibiting insulin/IGF-1 signaling, reducing food intake and impairing mitochondrial function, respectively. We found that 43 lysosome genes exhibit reduced expression with age, including genes encoding subunits of the proton pump V-ATPase and cathepsin proteases. The expression of lysosome genes is upregulated in the long-lived mutants, and this upregulation requires the functions of DAF-16/FOXO and SKN-1/NRF2 transcription factors. Impairing lysosome function affects clearance of aggregate-prone proteins and disrupts lifespan extension in daf-2, eat-2 and isp-1 worms. Our data indicate that lysosome function is modulated by multiple longevity pathways and is important for lifespan extension.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Yanan Sun

    National Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China
    Competing interests
    No competing interests declared.
  2. Meijiao Li

    School of Life Sciences, Yunnan University, Kunming, China
    Competing interests
    No competing interests declared.
  3. Dongfeng Zhao

    National Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China
    Competing interests
    No competing interests declared.
  4. Xin Li

    National Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China
    Competing interests
    No competing interests declared.
  5. Chonglin Yang

    School of Life Sciences, Yunnan University, Kunming, China
    Competing interests
    No competing interests declared.
  6. Xiaochen Wang

    National Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China
    For correspondence
    wangxiaochen@ibp.ac.cn
    Competing interests
    Xiaochen Wang, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4344-0925

Funding

Ministry of Science and Technology of the People's Republic of China (2016YFA0500203)

  • Xiaochen Wang

National Natural Science Foundation of China (3163001,91754203)

  • Xiaochen Wang

The Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000)

  • Xiaochen Wang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Mahak Sharma, Indian Institute of Science Education and Research Mohali, India

Publication history

  1. Received: February 4, 2020
  2. Accepted: May 25, 2020
  3. Accepted Manuscript published: June 2, 2020 (version 1)
  4. Version of Record published: June 5, 2020 (version 2)

Copyright

© 2020, Sun et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yanan Sun
  2. Meijiao Li
  3. Dongfeng Zhao
  4. Xin Li
  5. Chonglin Yang
  6. Xiaochen Wang
(2020)
Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans
eLife 9:e55745.
https://doi.org/10.7554/eLife.55745

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