Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans

Tan, Lin; Zheng, Zhuo-Ya; Huang, Lv; Sulian, LI; Wu, Gui-Sheng; Luo, Huai‐Rong

doi:10.3389/fphar.2022.931886

Cited by 10 publications

(7 citation statements)

References 47 publications

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“…The insulin/IGF-1 signal pathway is necessary for the extended survival of overexpressed heat shock proteins. More importantly, APPA preserves protein homeostasis [ 62 ]. Daf-16 ’s downstream transcription factor, sod-3 , is easily triggered to control antioxidant detoxification.…”

Section: Discussionmentioning

confidence: 99%

APPA Increases Lifespan and Stress Resistance via Lipid Metabolism and Insulin/IGF-1 Signal Pathway in Caenorhabditis elegans

Wang,

Lin,

Cao

et al. 2023

IJMS

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Animal studies have proven that 1-acetyl-5-phenyl-1H-pyrrol-3-yl acetate (APPA) is a powerful antioxidant as a novel aldose reductase inhibitor independently synthesized by our laboratory; however, there is no current information on APPA’s anti-aging mechanism. Therefore, this study examined the impact and mechanism of APPA’s anti-aging and anti-oxidation capacity using the Caenorhabditis elegans model. The results demonstrated that APPA increases C. elegans’ longevity without affecting the typical metabolism of Escherichia coli OP50 (OP50). APPA also had a non-toxic effect on C. elegans, increased locomotor ability, decreased the levels of reactive oxygen species, lipofuscin, and fat, and increased anti-stress capacity. QRT-PCR analysis further revealed that APPA upregulated the expression of antioxidant genes, including sod-3, gst-4, and hsp-16.2, and the critical downstream transcription factors, daf-16, skn-1, and hsf-1 of the insulin/insulin-like growth factor (IGF) receptor, daf-2. In addition, fat-6 and nhr-80 were upregulated. However, the APPA’s life-prolonging effects were absent on the daf-2, daf-16, skn-1, and hsf-1 mutants implying that the APPA’s life-prolonging mechanism depends on the insulin/IGF-1 signaling system. The transcriptome sequencing also revealed that the mitochondrial route was also strongly associated with the APPA life extension, consistent with mev-1 and isp-1 mutant life assays. These findings aid in the investigation of APPA’s longevity extension mechanism.

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Section: Discussionmentioning

confidence: 99%

APPA Increases Lifespan and Stress Resistance via Lipid Metabolism and Insulin/IGF-1 Signal Pathway in Caenorhabditis elegans

Wang,

Lin,

Cao

et al. 2023

IJMS

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“…The mechanism found after further investigation was based on the involvement of DAF-16/FOXO, SKN-1 and heat shock factor 1 (HSF-1) signaling pathways. CA also caused a reduction in the aggregation of toxic proteins Aβ and α-synuclein, and improved the motility of the organisms ( 113 ) ( Table 2 ).…”

Section: Phytochemical Antioxidant Compounds That Act As Activators O...mentioning

confidence: 99%

Natural antioxidants that act against Alzheimer’s disease through modulation of the NRF2 pathway: a focus on their molecular mechanisms of action

Sidiropoulou,

Metaxas,

Kourti

2023

Front. Endocrinol.

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Characterized by a complex pathophysiology that includes the intraneuronal formation of neurofibrillary tangles and the extracellular deposition of β-amyloid plaques, Alzheimer’s disease (AD) is a terminal neurodegenerative disease that causes dementia in older adults. Oxidative stress in the brain is considered as one of the contributing factors to the pathogenesis of AD, and thus, antioxidants have attracted much interest as potential therapeutic agents against the disorder. Natural antioxidants are typically characterized by low acute and chronic toxicity, which facilitates their potential therapeutic application. One important molecular target for the beneficial effects of natural antioxidants is the nuclear factor erythroid-derived 2-related factor 2 (NFE2L2/NRF2). NRF2 is a key transcription factor that orchestrates the cellular antioxidant response through regulating the expression of oxidative stress-related genes harboring the antioxidant response element (ARE) in their promoters. Indeed, in the case of excessive oxidative damage, NRF2 migrates to the nucleus and binds to ARE, activating the transcription of antioxidant protector genes. There is increasing evidence that NRF2 is implicated in AD pathology through dysfunction and altered localization, which renders it as a potential therapeutic target for AD. Thus, this review summarizes the most recent (2018-2023) advances on the NRF2-modulating activity of natural antioxidants observed in vitro and in AD animal models. This information will help elucidate the molecular mechanisms governing the antioxidant activity of such phytochemicals to highlight their therapeutic potential against common neurodegenerative diseases, such as AD.

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“…Chaperone‐mediated protein folding and quality control mechanisms deteriorate with aging and predispose the organism to reduction in both healthspan and lifespan (Ploumi et al., 2023). Impaired proteostasis is characteristic of various age‐related diseases such as AD and Parkinson's disease, atherosclerosis, and amyothrophic lateral sclerosis (Tan et al., 2022). The dynamic fluctuations in the proteome could also be due to external stimuli and stressors such as ambient temperature changes.…”

Section: “Old” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

“…Similarly, camplanthoside A activated the proetestasis response through HSP‐1‐mediated mechanism that resulted in increased expression of HSP‐4, HSP‐6, and HSP‐60 and reduced the accumulation of α‐synuclein and β‐amyloid in C. elegans AD and PD models. Further, the stabilized protein homeostasis from the camplanthoside A supplementation induced DAF‐16‐dependent lifespan extension (Tan et al., 2022).…”

Section: “Old” Hallmarks Of Aging—longevity Perspectivementioning

confidence: 99%

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

Todorova,

Savova,

Mihaylova

et al. 2024

Food Frontiers

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The revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.

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Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans

Cited by 10 publications

References 47 publications

APPA Increases Lifespan and Stress Resistance via Lipid Metabolism and Insulin/IGF-1 Signal Pathway in Caenorhabditis elegans

APPA Increases Lifespan and Stress Resistance via Lipid Metabolism and Insulin/IGF-1 Signal Pathway in Caenorhabditis elegans

Natural antioxidants that act against Alzheimer’s disease through modulation of the NRF2 pathway: a focus on their molecular mechanisms of action

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

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