Affiliation:
1. College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610068, China
2. College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China
Abstract
Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been a challenge to isolate a single active molecule from them and verify the mechanism of anti-aging action. Drugs that inhibit senescence-associated secretory phenotypes (SASPs) are called “senomorphics”. In this study, arctigenin (ATG), a senomorphic, was screened from the Chinese medicine Fructus arctii using K6001 yeast replicative lifespan. Autophagy, oxidative stress, and telomerase activity are key mechanisms related to aging. We found that ATG may act through multiple mechanisms to become an effective anti-aging molecule. In exploring the effect of ATG on autophagy, it was clearly observed that ATG significantly enhanced autophagy in yeast. We further verified that ATG can enhance autophagy by targeting protein phosphatase 2A (PP2A), leading to an increased lifespan. Meanwhile, we evaluated the antioxidant capacity of ATG and found that ATG increased the activities of the antioxidant enzymes, thereby reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels to improve the survival of yeast under oxidative stress. In addition, ATG was able to increase telomerase activity by enhancing the expression of EST1, EST2, and EST3 genes in yeast. In conclusion, ATG exerts anti-aging effects through induction of autophagy, antioxidative stress, and enhancement of telomerase activity in yeast, which is recognized as a potential molecule with promising anti-aging effects, deserving in-depth research in the future.
Funder
National Key R&D Program of China
National Natural Science Foundation of China
Reference39 articles.
1. Digital health for aging populations;Chen;Nat. Med.,2023
2. Health and labor market effects of an unanticipated rise in retirement age. Evidence from the 2012 Italian pension reform;Ardito;Health Econ.,2023
3. Effects of lifespan-extending interventions on cognitive healthspan;Culig;Expert Rev. Mol. Med.,2023
4. Alessio, N., Squillaro, T., Lettiero, I., Galano, G., De Rosa, R., Peluso, G., Galderisi, U., and Di Bernardo, G. (2021). Biomolecular evaluation of piceatannol’s effects in counteracting the senescence of mesenchymal stromal cells: A new candidate for senotherapeutics?. Int. J. Mol. Sci., 22.
5. Anoectochilus roxburghii flavonoids extract ameliorated the memory decline and reduced neuron apoptosis via modulating SIRT1 signaling pathway in senescent mice;Zeng;J. Ethnopharmacol.,2022