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Cited by 204Genetics, Aging, and Longevity in Model OrganismsAutophagy in Disease and TherapyCalcium signaling and nucleotide metabolism

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

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Sun, Yanan, Li, Meijiao, Zhao, Dongfeng, Li, Xin, Yang, Chonglin, Wang, Xiaochen·2020·eLife
DOI 10.7554/elife.55745PMC PMC7274789
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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.

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  • At least five other PD-associated genes (LRRK2, UCHL2, VCP35, DJ-1, and SNCA) affect CMA.

    “At least five other genes that are associated with PD (but not LSDs) also affect CMA: LRRK2, UCHL2, VCP35, DJ-1, and SNCA, which encodes alpha-synuclein.149–153”

    From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [151]

    The Results sections on lysosome activity and aggregate clearance in C. elegans do not address whether the listed Parkinson’s disease-associated genes affect chaperone-mediated autophagy. Searches for the five gene names, CMA, Parkinson’s disease, and alpha-synuclein found no passage in our copy that speaks to the claim. (LLM, conf=0.75)

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Cited by

Sorted by citations

Authors
Sun, Y., Li, M., Zhao, D., Li, X., Yang, C., & Wang, X.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Yunnan University (CN)
Corresponding author
Wang, Xiaochen
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2020-06-02
Volume
9
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.55745
PMC
PMC7274789
OpenAlex
W3030118581
Cited by
204
References
3
Citations by year
2026: 27 · 2025: 45 · 2024: 44 · 2023: 37 · 2022: 28 · 2021: 19 · 2020: 4
FWCI
7.42
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Science and Technology of the People's Republic of China (2016YFA0500203)
  • National Natural Science Foundation of China (3163001, 91754203)
  • Chinese Academy of Sciences (Strategic Priority Research Program XDB19000000)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
lysosomes, aging, lifespan extension, longevity pathways, lysosomal function, lysosomal pH, lysosomal morphology, lysosomal degradation, insulin/IGF-1 signaling, daf-2, EAT-2, isp-1, DAF-16/FOXO, SKN-1/Nrf2, V-ATPase, cathepsins, protein aggregate clearance, Caenorhabditis elegans
MeSH terms
Animals, Insulin, Insulin-Like Growth Factor I, Longevity, Lysosomes, Receptor, Insulin, Signal Transduction, Caenorhabditis elegans, Caenorhabditis elegans Proteins

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