Cynaroside extends lifespan and improves the neurondegeneration diseases via insulin/IGF-1 signaling pathway in Caenorhabditis elegans

• Published in: Archives of gerontology and geriatrics 2024-07, Vol.122, p.105377, Article 105377
• Main Authors: Xiao, Yi, Zhang, Yan, Li, Linlu, Jiang, Nian, Yu, Changyan, Li, Sanhua, Zhu, Xinting, Liu, Fang, Liu, Yun
• Format: Article
• Language: English
• Subjects: Aging - drug effects; Aging - physiology; Animals; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cynaroside; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Insulin - metabolism; Insulin-Like Growth Factor I - metabolism; Insulin/IGF-1 signaling pathway; Lifespan; Longevity - drug effects; Luteolin - pharmacology; Neurodegeneration diseases; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - prevention & control; Signal Transduction - drug effects
• ISSN: 0167-4943; 1872-6976; 1872-6976
• DOI: 10.1016/j.archger.2024.105377

•Cynaroside promoted healthspan and lifespan in C. elegans.•Cynaroside extended healthspan via insulin/IGF-1 signaling pathway in C. elegans.•Cynaroside activated the Forkhead box O (FOXO) transcription factor DAF-16 in C. elegans.•Cynaroside improved neurodegeneration diseases through insulin/IGF-1 signaling pathway. The evolutionarily conserved insulin/IGF-1 signaling pathway plays a central role in aging and aging related diseases such as neurodegeneration diseases. Inhibition of insulin/IGF-1 signaling pathway has been proposed as an effective way to extend lifespan and delay neurodegeneration diseases in different organisms. Cynaroside (Cyn), a flavonoid contained in many medical plants and in vegetables, had been shown to exhibit pharmacological properties such as anti-inflammatory, anti-tumor, and anti-oxidant effects. The study demonstrated that lifespan extension and neurodegeneration diseases improving could be achieved by targeting evolutionarily conserved insulin/IGF-1 pathway through using pharmacological interventions. Via using this approach in tractable model Caenorhabditis elegans, we found that 10 μM Cynaroside significantly promoted the healthy lifespan in wild-type animals. Furthermore, via genetic screen, we showed that Cynaroside acted on IGF-1-R /DAF-2, which was followed by the activation of transcription factor DAF-16/FOXO to extend the healthy lifespan. Intriguingly, Cynaroside also improved neurodegeneration diseases such as Alzheimer's and polyglutamine disease by suppressing insulin/IGF-1 signaling pathway. Our work suggests that Cynaroside may be a promising candidate for the prevention and treatment of aging and neurodegeneration diseases.