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The proprotein convertase BLI-4 Is required for axenic dietary restriction mediated longevity in Caenorhabditis elegans

Ping Wu (UGent) , Lieselot Vandemeulebroucke, Huaihan Cai (UGent) and Bart Braeckman (UGent)
(2025) AGING CELL. 24(7).
Author
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Abstract
Dietary restriction (DR) is a well-established method for extending lifespan across various species, including C. elegans. Among the different DR regimens, axenic dietary restriction (ADR), in which worms are grown in a nutrient-rich sterile liquid medium, yields the most powerful lifespan extension. However, the molecular mechanisms underlying this longevity phenotype remain largely unexplored. Through a pilot screen of candidate genes, we identified the proprotein convertase BLI-4 as a crucial factor in neurons for modulating lifespan under ADR conditions. BLI-4's role appears to be specific to ADR, as it does not significantly impact longevity under other DR regimens. We further explored the involvement of different bli-4 isoforms and found that isoforms b, f, i and j redundantly contribute to the ADR-mediated lifespan extension, while the bli-4d isoform is mainly involved in development. Proteomics analysis revealed that the loss of BLI-4 function under ADR conditions specifically downregulates GOLG-2, involved in Golgi complex organization. This gene also partially mediates the longevity effects of BLI-4 under ADR conditions. Our findings highlight the importance of neuronal BLI-4 and its downstream targets in regulating lifespan extension induced by ADR in C. elegans.
Keywords
axenic dietary restriction (ADR), BLI-4, Caenorhabditis elegans, longevity, neuropeptide signaling, proprotein convertase, proteomics, LIFE-SPAN EXTENSION, C-ELEGANS, STRESS RESISTANCE, SIGNALING PATHWAY, GENE-EXPRESSION, INSULIN, ENCODES, NEURONS, INHIBITION, VESICLE

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MLA
Wu, Ping, et al. “The Proprotein Convertase BLI-4 Is Required for Axenic Dietary Restriction Mediated Longevity in Caenorhabditis Elegans.” AGING CELL, vol. 24, no. 7, 2025, doi:10.1111/acel.70058.
APA
Wu, P., Vandemeulebroucke, L., Cai, H., & Braeckman, B. (2025). The proprotein convertase BLI-4 Is required for axenic dietary restriction mediated longevity in Caenorhabditis elegans. AGING CELL, 24(7). https://doi.org/10.1111/acel.70058
Chicago author-date
Wu, Ping, Lieselot Vandemeulebroucke, Huaihan Cai, and Bart Braeckman. 2025. “The Proprotein Convertase BLI-4 Is Required for Axenic Dietary Restriction Mediated Longevity in Caenorhabditis Elegans.” AGING CELL 24 (7). https://doi.org/10.1111/acel.70058.
Chicago author-date (all authors)
Wu, Ping, Lieselot Vandemeulebroucke, Huaihan Cai, and Bart Braeckman. 2025. “The Proprotein Convertase BLI-4 Is Required for Axenic Dietary Restriction Mediated Longevity in Caenorhabditis Elegans.” AGING CELL 24 (7). doi:10.1111/acel.70058.
Vancouver
1.
Wu P, Vandemeulebroucke L, Cai H, Braeckman B. The proprotein convertase BLI-4 Is required for axenic dietary restriction mediated longevity in Caenorhabditis elegans. AGING CELL. 2025;24(7).
IEEE
[1]
P. Wu, L. Vandemeulebroucke, H. Cai, and B. Braeckman, “The proprotein convertase BLI-4 Is required for axenic dietary restriction mediated longevity in Caenorhabditis elegans,” AGING CELL, vol. 24, no. 7, 2025.
@article{01JRF9Z5CMWFT63865MC15QX7M,
  abstract     = {{Dietary restriction (DR) is a well-established method for extending lifespan across various species, including C. elegans. Among the different DR regimens, axenic dietary restriction (ADR), in which worms are grown in a nutrient-rich sterile liquid medium, yields the most powerful lifespan extension. However, the molecular mechanisms underlying this longevity phenotype remain largely unexplored. Through a pilot screen of candidate genes, we identified the proprotein convertase BLI-4 as a crucial factor in neurons for modulating lifespan under ADR conditions. BLI-4's role appears to be specific to ADR, as it does not significantly impact longevity under other DR regimens. We further explored the involvement of different bli-4 isoforms and found that isoforms b, f, i and j redundantly contribute to the ADR-mediated lifespan extension, while the bli-4d isoform is mainly involved in development. Proteomics analysis revealed that the loss of BLI-4 function under ADR conditions specifically downregulates GOLG-2, involved in Golgi complex organization. This gene also partially mediates the longevity effects of BLI-4 under ADR conditions. Our findings highlight the importance of neuronal BLI-4 and its downstream targets in regulating lifespan extension induced by ADR in C. elegans.}},
  articleno    = {{e70058}},
  author       = {{Wu, Ping and Vandemeulebroucke, Lieselot and Cai, Huaihan and Braeckman, Bart}},
  issn         = {{1474-9718}},
  journal      = {{AGING CELL}},
  keywords     = {{axenic dietary restriction (ADR),BLI-4,Caenorhabditis elegans,longevity,neuropeptide signaling,proprotein convertase,proteomics,LIFE-SPAN EXTENSION,C-ELEGANS,STRESS RESISTANCE,SIGNALING PATHWAY,GENE-EXPRESSION,INSULIN,ENCODES,NEURONS,INHIBITION,VESICLE}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{14}},
  title        = {{The proprotein convertase BLI-4 Is required for axenic dietary restriction mediated longevity in Caenorhabditis elegans}},
  url          = {{http://doi.org/10.1111/acel.70058}},
  volume       = {{24}},
  year         = {{2025}},
}
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