Aging-US: Sulforaphane promotes C. elegans longevity and healthspan02-02-2021
Aging-US published "Sulforaphane promotes C. elegans longevity and healthspan via DAF- 16/DAF-2 insulin/IGF-1 signaling" which reported that the broccoli-derived isothiocyanate sulforaphane inhibits inflammation, oxidative stress and cancer, but its effect on healthspan and longevity are unclear.
The authors used the C. elegans nematode model and fed the wildtype and 9 mutant strains ±sulforaphane.
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.
The results in this Aging-US research output, indicate that sulforaphane prolongs the lifespan and healthspan of C. elegans through insulin/IGF-1 signaling. They provide the basis for a nutritional sulforaphane-enriched strategy for the promotion of healthy aging and disease prevention.
Dr. Ingrid Herr from The University of Heidelberg said, "The risk of cancer, cardiovascular disease, and neurodegeneration rises dramatically later in life."
Pak choy, which is one of the most widely consumed Brassica vegetables in Asian countries, have been reported to enhance antioxidant activity in a cell-free system and exert anti-aging effects in the nematode Caenorhabditis elegans.
C. elegans is one of the most widely used models for aging research due to its short lifespan of approximately 4 weeks and highly conserved key aging-related signaling molecules .
Here, the authors asked whether sulforaphane may influence the lifespan and healthspan of C. elegans.
Figure 3. Sulforaphane delays age-associated physiological decline. (A) L4 larvae were exposed to 100 μM sulforaphane (SF) or not (CO), and 20 worms per group were used for evaluation. Pharyngeal pumping was measured on days 6, 9 and 12 by the evaluation of the opening of the corpus (anterior pharynx, green arrow, image on the right) and the terminal bulb (red arrow), which contract and relax synchronously during pharyngeal pumping. The pump frequency per minute was calculated and is shown in the diagram on the left. (B) In L4 larvae treated as described above, the number of body bends (images on the right) per minute was evaluated (diagram on the left) to assess mobility. (C) At day 12 after sulforaphane treatment, blue autofluorescence, representing lipofuscin accumulation (images on the right), was detected by fluorescence microscopy. The blue autofluorescence in the figure indicates the accumulation of lipofuscin. The relative fluorescence intensity was evaluated by using ImageJ software, and the fluorescence of the untreated nematodes was set as 1. The scale bar indicates 0.1 mm. (D) L4 larvae were treated with sulforaphane (SF) or not (CO). Twenty-four hours later (Day 1), the number of eggs laid was counted under the microscope daily for 7 days. The number of eggs laid each day and the total number of eggs are shown in the diagram on the left. The green arrow in the diagram on the right indicates eggs in a worm, and the red arrow indicates eggs that are being laid by the worm. The data are shown as the mean ± SD as evaluated by Student's t test using Prism 6.0. *P< 0.05, **P < 0.01.
They found that sulforaphane significantly extends the lifespan of C. elegans and delays age-related phenotype changes.
The analysis of wild-type C. elegans and 9 mutant strains revealed that sulforaphane inhibited DAF-2 insulin/insulin receptor signaling and thereby increased DAF-16 nuclear translocation, resulting in the expression of the sod-3, mtl-1 and gst-4 target genes, which are known mediators of longevity in C. elegans.
The Herr Research Team concluded in their Aging-US Research Paper, "we are the first to report that sulforaphane prolongs the lifespan and increases the healthspan of C. elegans through the inhibition of DAF- 2/insulin/IGF-1 signaling and the activation of DAF- 16/FOXO nuclear transcription in C. elegans. Our study provides a promising hint regarding the suitability of sulforaphane as a new anti-aging drug. However, additional studies in invertebrates and mammalian model organisms are necessary to expand our findings."
Full Text - https://www.aging-us.com/article/202512/text
Correspondence to: Ingrid Herr email: firstname.lastname@example.org
Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.