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HSF-1 和 SIR-2.1 相关的胰岛素样信号通路参与了枸杞(Lycium spp.)提取物对秀丽隐杆线虫寿命延长的促进作用。

HSF-1 and SIR-2.1 linked insulin-like signaling is involved in goji berry (Lycium spp.) extracts promoting lifespan extension of Caenorhabditis elegans.

机构信息

Overseas Expertise Introduction Center for Discipline Innovation of Food Nutrition and Human Health (111 Center), School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China.

出版信息

Food Funct. 2021 Sep 7;12(17):7851-7866. doi: 10.1039/d0fo03300f. Epub 2021 Jul 9.

DOI:10.1039/d0fo03300f
PMID:34240728
Abstract

The anti-cancer, vision-improving, and reproduction-enhancing effects of goji berry have been generally recognized, but its role in anti-aging is rarely studied in depth. Therefore, two widely-circulated goji berries, Lycium ruthenicum Murr. (LRM) and Lycium Barbarum. L (LB), were selected to explore their effects on extending lifespan and enhancing defense against extrinsic stress and to uncover the mechanism of action through genetic study. The results showed that supplementation with high-dose LRM (10 mg mL) and LB (100 mg mL) extracts significantly extended the lifespan of Caenorhabditis elegans (C. elegans) by 25.19% and 51.38%, respectively, accompanied by the improved stress tolerance of C. elegans to paraquat-induced oxidation, UV-B irradiation and heat shock. Furthermore, LRM and LB extracts remarkably enhanced the activities of antioxidant enzymes including SOD and CAT in C. elegans, while notably decreased the lipofuscin level. Further genetic research demonstrated that the expression levels of key genes daf-16, sod-2, sod-3, sir-2.1 and hsp-16.2 in C. elegans were up-regulated by the intervention with LRM and LB, while that of the age-1 level was down-regulated. Moreover, the daf-16 (mu86) I, sir-2.1 (ok434) IV and hsf-1 (sy441) I mutants reversed the longevity effect brought about by LRM or LB, which confirmed that these genes were required in goji berry-mediated lifespan extension. Therefore, we conclude that HSF-1 and SIR-2.1 act collaboratively with the insulin/IGF signaling pathway (IIS) in a daf-16-independent mode. The present study indicated goji berry as a potential functional food to alleviate the symptoms of aging.

摘要

枸杞的抗癌、改善视力和增强生殖能力的作用已得到普遍认可,但很少深入研究其抗衰老作用。因此,选择了两种广泛流传的枸杞,黑果枸杞(LRM)和宁夏枸杞(LB),通过遗传研究来探索它们延长寿命和增强抵御外在压力的作用,并揭示其作用机制。结果表明,高剂量 LRM(10mg/ml)和 LB(100mg/ml)提取物显著延长了秀丽隐杆线虫(C. elegans)的寿命,分别延长了 25.19%和 51.38%,同时提高了 C. elegans 对百草枯诱导氧化、UV-B 辐射和热休克的应激耐受性。此外,LRM 和 LB 提取物显著增强了 C. elegans 中抗氧化酶如 SOD 和 CAT 的活性,同时明显降低了脂褐素水平。进一步的遗传研究表明,LRM 和 LB 干预显著上调了 C. elegans 中关键基因 daf-16、sod-2、sod-3、sir-2.1 和 hsp-16.2 的表达水平,而下调了 age-1 水平。此外,daf-16(mu86)I、sir-2.1(ok434)IV 和 hsf-1(sy441)I 突变体逆转了 LRM 或 LB 带来的长寿效应,这证实了这些基因是枸杞介导的寿命延长所必需的。因此,我们得出结论,HSF-1 和 SIR-2.1 以 daf-16 非依赖性方式与胰岛素/IGF 信号通路(IIS)协同作用。本研究表明枸杞是一种有潜力的功能性食品,可以缓解衰老症状。

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