Research Paper Volume 13, Issue 2 pp 1649—1670
Sulforaphane promotes C. elegans longevity and healthspan via DAF-16/DAF-2 insulin/IGF-1 signaling
- 1 Molecular OncoSurgery, Section Surgical Research, Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany
- 2 Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany
Received: July 28, 2020 Accepted: December 18, 2020 Published: January 20, 2021https://doi.org/10.18632/aging.202512
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Copyright: © 2021 Qi 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.
The broccoli-derived isothiocyanate sulforaphane inhibits inflammation, oxidative stress and cancer, but its effect on healthspan and longevity are unclear. We used the C. elegans nematode model and fed the wildtype and 9 mutant strains ±sulforaphane. The lifespan, phenotype, pharyngeal pumping, mobility, lipofuscin accumulation, and RNA and protein expression of the nematodes were assessed by using Kaplan-Meier survival analysis, in vivo live imaging, fluorescence microscopy, and qRT-PCR. Sulforaphane increased the lifespan and promoted a health-related phenotype by increasing mobility, appetite and food intake and reducing lipofuscin accumulation. Mechanistically, sulforaphane inhibited DAF-2-mediated insulin/insulin-like growth factor signaling and its downstream targets AGE-1, AKT-1/AKT-2. This was associated with increased nuclear translocation of the FOXO transcription factor homolog DAF-16. In turn, the target genes sod-3, mtl-1 and gst-4, known to enhance stress resistance and lifespan, were upregulated. These results indicate that sulforaphane prolongs the lifespan and healthspan of C. elegans through insulin/IGF-1 signaling. Our results provide the basis for a nutritional sulforaphane-enriched strategy for the promotion of healthy aging and disease prevention.
C. elegans: Caenorhabditis elegans; CGC: Caenorhabditis Genetics Center; ctl: Catalase-2; DHE: Dihydroethidium; dod-3: downstream of DAF-16; gst-4: glutathione S-transferase 4; 2-EOH: 2-Hydroxyethidium; E. coli: Escherichia coli; IGF: Insulin-like growth factor; IIS: Insulin/insulin-like growth factor signaling; MIC: Minimum inhibitory concentration; mt: Mutant; mtl-1: metallothionein-1; NGM: Nematode growth medium; ROS: Reactive oxygen species; sod-3: superoxide dismutase 3.