Curcumin supplementation increases longevity and antioxidant capacity in Caenorhabditis elegans

Abstract

Curcumin is well known as a potent antioxidant and free radical scavenger and has great potential for anti-aging applications. In this study, we investigate the molecular mechanism of curcumin in prolonging the lifespan of C. elegans. Four concentrations of curcumin (10, 25, 50, and 100 µM) were administered, and the optimal treatment concentration was determined by analyzing the nematode lifespan, physiology, and biochemistry. Additionally, RNA-seq and qRT-PCR were performed to explore the antioxidant effect of curcumin and its underlying mechanism. Results revealed that curcumin could significantly improve the survival capacity of C. elegans without influencing its growth. Curcumin was observed to significantly decrease the levels of reactive oxygen species (ROS) under extreme conditions such as heat stress and paraquat stress. In addition, curcumin increased the amount of nematode mitochondrial DNA (mtDNA) replication. RNA-seq results revealed that the underlying mechanism of curcumin in C. elegans is related to the mitogen-activated protein kinase (MAPK) pathway. qRT-PCR results confirmed that the expression of oxidative stress-related genes (sod-1, sod-2, sod-3, gst-4) was increased, and the expression of MAPK signaling pathway-related genes (sek-1, pmk-1, nsy-1) was significantly downregulated. Furthermore, the administration of curcumin extended the lifespan of nematodes, potentially through the enhancement of oxidative stress resistance and the downregulation of the MAPK signaling pathway. These findings improve our understanding of both lifespan extension and the potential mechanism of curcumin in C. elegans.

Simira cordifolia protects against metal induced-toxicity in Caenorhabditis elegans

“…It is possible that chlorogenic acid, one of the compounds detected in the phytochemical analysis of S. cordifolia extract, is linked to the observed results, as its ability to extend the worm’s lifespan and enhance thermotolerance has been previously reported ( del valle-Carranza, et al, 2020 ). Pre-exposure of worms (L1 to L4) to HAE- S c ameliorates high temperature-induced lethality, which may be related to the plant species’ ability to enhance the antioxidant system, as observed in other pigmented extracts such as curcumin ( Xu et al, 2023 ). However, more comprehensive research will be necessary to enable the identification of the functional chemical components present in the extract, as well as to understand their interactions.…”

“…Age-synchronized worms were cultured on NGM plates containing E. coli OP50 as a food source, and kept in a 20°C incubator until use. OP50 was grown in Luria-Bertani (LB) broth for 24 h in an incubator at 37°C ( Xu et al, 2023 ).…”

Network pharmacology analysis and experimental validation of <italic>Anemarrhenae Rhizoma</italic> in treating Alzheimer<bold>’</bold>s disease

“…根据PPI网络结果，本研究筛选出ALB、Akt1、TNF、EGFR、VEGFA、mTOR、APP等关键靶点，其中ALB、Akt1的度值最高，提示这两个靶点可能是知母治疗AD最关键靶点。其中ALB多用于肿瘤研究 ［ 17 ］ ，而Akt1常用于AD研究。 Akt1 基因编码的是丝氨酸/苏氨酸激酶，细胞外的信号激活可通过PI3K实现。KEGG结果显示，知母治疗AD通路中占比排序分别是神经活性配体-受体相互作用、PI3K/Akt信号通路、钙信号通路、内分泌抵抗、胰岛素抵抗、神经营养因子信号通路、糖尿病并发症中的AGE/RAGE信号通路等通路，这些信号通路与AD的发病机制均相关。神经系统中最基本的单位是神经元，而神经元是信息交流与学习的重要功能单位，神经活性配体-受体相互作用是在记忆和学习方面起主要作用 ［ 18 ］ 。而PI3K/Akt信号通路在AD的发病机制中至关重要。有研究显示，PI3K/Akt信号通路的增强可加强自噬，从而增加Aβ的清除 ［ 19 ］ 。另外，PI3K/Akt通路是与细胞防御相关的多功能典型信号通路，该通路的激活参与了氧化还原反应的调节，并在保护细胞免受氧化应激方面起着关键作用 ［ 20 ］ 。PI3K/Akt信号通路还可以通过调控GSK-3β磷酸化来影响APP和Aβ的生成，研究表明，GSK-3β是PI3K/Akt通路下游的关键元件，与AD中Aβ沉积相关，Akt介导的磷酸化可抑制其表达，抑制GSK-3β活性可改善认知缺陷并降低氧化应激反应 ［ 20 - 21 ］ 。抗氧化反应元件位于细胞核中，当受到应激刺激时可被激活，导致抗氧化反应元件下游基因的转录和表达，包括抗氧化剂、抗氧化蛋白酶体、Ⅱ期解毒酶等 ［ 22 ］ 。抗氧化反应元件被激活后会引起抗氧化级联反应，几种内源性抗氧化酶，如HO-1、NQO1在氧化应激级联反应中可被进一步调节 ［ 23 - 24 ］ ，而这两个蛋白是PI3K/Akt信号通路中与氧化应激相关的重要蛋白 ［ 25 - 26 ］ 。在氧化应激条件下，细胞内活性氧数增加，导致细胞膜结构和功能破坏 ［ 27 ］ 。中枢神经系统极易受到氧化应激的影响，AD患者大脑中存在过多的活性氧和生物活性物质，可以促进Aβ斑块的沉积，Aβ蛋白在大脑中发挥破坏作用，包括降低突触可塑性、抑制海马的长期增强和产生活性氧等 ［ 23 ， 28 ］ 。在AD中，β-分泌酶和γ-分泌酶产生具有淀粉样蛋白特征的APP成分，其中BACE1是参与APP代谢的β-分泌酶，可通过裂解APP生成Aβ ［ 3 ， 29 ］ 。随着年龄的增长，β-分泌酶在AD患者大脑中的表达水平也逐渐升高，在细胞模型中，氧化应激以及缺血缺氧、能量剥夺等情况均可促进BACE1的高表达 ［ 3 ］ 。…”

Mitochondria in the Spotlight: C. elegans as a Model Organism to Evaluate Xenobiotic-Induced Dysfunction

“…Aging: The ETC reactions throughout the whole lifetime of any species are a source of continuous electron leakage, and incomplete oxygen reduction at Complex IV during C. elegans life leads to ROS production and oxidative stress, as occurs in mammals [14]. As evidence, supplementation with antioxidants can extend the nematode's longevity by attenuating oxidative stress and aging-related endpoints such as locomotion and lipofuscin levels [39]. Furthermore, the accumulation of mutations in mitochondrial DNA [40] and the deregulation of the mitochondrial unfolded protein response (UPRmt) [41] contribute to the aging process in worms.…”