Research Paper Volume 15, Issue 1 pp 21—36

The innate immune signaling component FBXC-58 mediates dietary restriction effects on healthy aging in Caenorhabditis elegans

Jeong-Hoon Hahm1, , Farida S. Nirmala1,2, , Pyeong Geun Choi1,2, , Hyo-Deok Seo1, , Tae Youl Ha1,2, , Chang Hwa Jung1,2, , Jiyun Ahn1,2, ,

  • 1 Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun 55365, South Korea
  • 2 Department of Food Biotechnology, University of Science and Technology, Daejeon-si 34113, South Korea

Received: September 1, 2022       Accepted: December 29, 2022       Published: January 6, 2023
How to Cite

Copyright: © 2023 Hahm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Dietary restriction (DR) is a highly effective and reproducible intervention that prolongs longevity in many organisms. The molecular mechanism of action of DR is tightly connected with the immune system; however, the detailed mechanisms and effective downstream factors of immunity that mediate the beneficial effects of DR on aging remain unknown. Here, to investigate the immune signaling that mediates DR effects, we used Caenorhabditis elegans, which has been widely used in research, to understand the underlying molecular mechanisms of aging and immunity. We found that the F-box gene, fbxc-58, a regulator of the innate immune response, is a novel mediator of DR effects on extending the health span of C. elegans. fbxc-58 is upregulated by DR and is necessary for DR-induced lifespan extension and physical health improvement in C. elegans. Furthermore, through DR, fbxc-58 prevents disintegration of the mitochondrial network in body wall muscle during aging. We found that fbxc-58 is a downstream target of the ZIP-2 and PHA-4 transcription factors, the well-known DR mediator, and fbxc-58 extends longevity in DR through an S6 kinase-dependent pathway. We propose that the novel DR effector, fbxc-58, could provide a new mechanistic understanding of the effects of DR on healthy aging and elucidate the signaling mechanisms that link immunity and DR effects with aging.


C. elegans: Caenorhabditis elegans; CGC: Caenorhabditis Genetics Center; NGM: Nematode growth medium; fbxc-58: F-box C protein-58; DR: Dietary Restriction; PA14: Pseudomonas aeruginosa; RNAi: RNA interference; ML: Median Lifespan; MV: Maximum Velocity; S6K: S6 Kinase; LDF: Low density food; OD: Optical density; FUDR: 2′-Deoxy-5-fluorouridine; GFP: Green fluorescent protein.