Paederia scandens(Lour.)Merris a substance exhibiting medicine–food homology (MFH), commonly used in China. However, the antioxidant and anti-aging effects ofpaederoside(PSG) have not been thoroughly investigated; therefore, in this study,Caenorhabditis elegans(C. elegans) was treated with PSG to investigate these effects. We found that 50, 80, and 100 μg/mL of PSG could prolong the lifespan ofC. elegans, and administration of 100 μg/mL PSG significantly reduced the accumulation of lipofuscin. Under conditions of oxidative stress, RT-qPCR analysis revealed that PSG treatment significantly up-regulated the expression of key antioxidant geneskn-1and longevity-associated genedaf-16. In addition, PSG increased the activity of the antioxidant enzymes SOD and CAT and reduced the level of MDA. When DAF-2 activity is reduced or inhibited inC. elegans, DAF-16 and SKN-1 are activated and translocate to the nucleus to promote stress resistance and prolong lifespan. Finally, by utilizing HeLa cell models, we demonstrated that the core component ofPaederia scandens, PSG, promotes targeted degradation of IGF1R through the ubiquitin–proteasome system. Our results suggest that feedingC. elegansPSG is effective in extending this organism’s lifespan by improving oxidative stress resistance; thus, PSG has significant potential for development as an anti-aging food product and drug.
Jia-Jun Tu,Zhen-Zhen Yu,Mei-Ling Ou,Jin-Xiong Cen,Kun Xue,Jing Zhou,Shao-Jun Li,Guo-Dong Lu
Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans . The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn- 1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1 (km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.
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