Molecular OncoSurgery, Section Surgical Research, Department of General, Visceral and Transplant Surgery, University of Heidelberg, Heidelberg, Germany.
Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.
Aging (Albany NY). 2021 Jan 20;13(2):1649-1670. doi: 10.18632/aging.202512.
The broccoli-derived isothiocyanate sulforaphane inhibits inflammation, oxidative stress and cancer, but its effect on healthspan and longevity are unclear. We used the 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, 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 DAF16. In turn, the target genes , and , known to enhance stress resistance and lifespan, were upregulated. These results indicate that sulforaphane prolongs the lifespan and healthspan of 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.
西兰花衍生的异硫氰酸酯萝卜硫素可抑制炎症、氧化应激和癌症，但它对健康寿命和长寿的影响尚不清楚。我们使用线虫模型并喂食野生型和 9 种突变株 ±萝卜硫素。通过 Kaplan-Meier 生存分析、实时成像、荧光显微镜和 qRT-PCR 评估线虫的寿命、表型、咽泵动、运动性、脂褐素积累以及 RNA 和蛋白质表达。萝卜硫素通过增加运动性、食欲和食物摄入以及减少脂褐素积累，延长了线虫的寿命并促进了与健康相关的表型。在机制上，萝卜硫素抑制了 DAF-2 介导的胰岛素/胰岛素样生长因子信号及其下游靶标 AGE-1、AKT-1/AKT-2。这与 FOXO 转录因子同源物 DAF16 的核易位增加有关。反过来，已知增强应激抗性和寿命的靶基因 、 和 被上调。这些结果表明，萝卜硫素通过胰岛素/IGF-1 信号延长线虫的寿命和健康寿命。我们的研究结果为促进健康衰老和预防疾病的营养富集萝卜硫素策略提供了依据。
