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Large extension of Caenorhabditis elegans lifespan in diluted axenic medium : a balancing act between different survival responses

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Abstract
Axenic dietary restriction (ADR) represents a powerful and unique DR regimen for C. elegans as it robustly extends lifespan independently of well-known key genes associated with DR, such as those of insulin/IGF-1 signaling, skn-1, and pha-4. Here, we analyze C. elegans survival in a dilution series of axenic medium to explore the dependency of lifespan extension on nutrient availability. We find a non-linear relationship between lifespan and axenic nutrient levels with a four-fold axenic dilution yielding peak longevity. Notably, lifespan extension at specific dilutions permits maintenance of reproductive potential and survivability after bacterial reintroduction, indicating a partial reliance on adult reproductive diapause mechanisms. Genetic analyses found the involvement of AMPK/aak-2, sir-2.1, and cbp-1 in mediating lifespan extension across the axenic dilution spectrum, the essential role of daf-16 and hlh-30 under severe nutrient scarcity, and the specific contribution of bli-4 to standard ADR longevity. These findings elucidate that C. elegans lifespan extension under different levels of nutrient restriction is governed by overlapping yet distinct genetic pathways.
Keywords
axenic dietary restriction (ADR), lifespan extension, adult reproductive diapause, nutrient dilution, C. elegans, axenic dietary restriction, DIETARY RESTRICTION, CELL-GROWTH, LONGEVITY, GENETICS, NEURONS, CBP-1

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Citation

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MLA
Wu, Ping, et al. “Large Extension of Caenorhabditis Elegans Lifespan in Diluted Axenic Medium : A Balancing Act between Different Survival Responses.” JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, vol. 80, no. 8, 2025, doi:10.1093/gerona/glaf129.
APA
Wu, P., Vandemeulebroucke, L., Guiritan, K. R., & Braeckman, B. (2025). Large extension of Caenorhabditis elegans lifespan in diluted axenic medium : a balancing act between different survival responses. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 80(8). https://doi.org/10.1093/gerona/glaf129
Chicago author-date
Wu, Ping, Lieselot Vandemeulebroucke, Kevin Rey Guiritan, and Bart Braeckman. 2025. “Large Extension of Caenorhabditis Elegans Lifespan in Diluted Axenic Medium : A Balancing Act between Different Survival Responses.” JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 80 (8). https://doi.org/10.1093/gerona/glaf129.
Chicago author-date (all authors)
Wu, Ping, Lieselot Vandemeulebroucke, Kevin Rey Guiritan, and Bart Braeckman. 2025. “Large Extension of Caenorhabditis Elegans Lifespan in Diluted Axenic Medium : A Balancing Act between Different Survival Responses.” JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 80 (8). doi:10.1093/gerona/glaf129.
Vancouver
1.
Wu P, Vandemeulebroucke L, Guiritan KR, Braeckman B. Large extension of Caenorhabditis elegans lifespan in diluted axenic medium : a balancing act between different survival responses. JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES. 2025;80(8).
IEEE
[1]
P. Wu, L. Vandemeulebroucke, K. R. Guiritan, and B. Braeckman, “Large extension of Caenorhabditis elegans lifespan in diluted axenic medium : a balancing act between different survival responses,” JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, vol. 80, no. 8, 2025.
@article{01JXZ27HC2WDC1X515YXX9RVCQ,
  abstract     = {{Axenic dietary restriction (ADR) represents a powerful and unique DR regimen for C. elegans as it robustly extends lifespan independently of well-known key genes associated with DR, such as those of insulin/IGF-1 signaling, skn-1, and pha-4. Here, we analyze C. elegans survival in a dilution series of axenic medium to explore the dependency of lifespan extension on nutrient availability. We find a non-linear relationship between lifespan and axenic nutrient levels with a four-fold axenic dilution yielding peak longevity. Notably, lifespan extension at specific dilutions permits maintenance of reproductive potential and survivability after bacterial reintroduction, indicating a partial reliance on adult reproductive diapause mechanisms. Genetic analyses found the involvement of AMPK/aak-2, sir-2.1, and cbp-1 in mediating lifespan extension across the axenic dilution spectrum, the essential role of daf-16 and hlh-30 under severe nutrient scarcity, and the specific contribution of bli-4 to standard ADR longevity. These findings elucidate that C. elegans lifespan extension under different levels of nutrient restriction is governed by overlapping yet distinct genetic pathways.}},
  articleno    = {{glaf129}},
  author       = {{Wu, Ping and Vandemeulebroucke, Lieselot and Guiritan, Kevin Rey and Braeckman, Bart}},
  issn         = {{1079-5006}},
  journal      = {{JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES}},
  keywords     = {{axenic dietary restriction (ADR),lifespan extension,adult reproductive diapause,nutrient dilution,C. elegans,axenic dietary restriction,DIETARY RESTRICTION,CELL-GROWTH,LONGEVITY,GENETICS,NEURONS,CBP-1}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{11}},
  title        = {{Large extension of Caenorhabditis elegans lifespan in diluted axenic medium : a balancing act between different survival responses}},
  url          = {{http://doi.org/10.1093/gerona/glaf129}},
  volume       = {{80}},
  year         = {{2025}},
}

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