Raspberry extract promoted longevity and stress tolerance via the insulin/IGF signaling pathway and DAF-16 in Caenorhabditis elegans

Increased consumption of fruits and vegetables is associated with a reduced risk of age-related functional decline and chronic diseases, which is primarily attributed to phytochemicals. Raspberries are rich in phytochemicals with a wide range of biological activities and health benefits. However, little is known about their effects on aging. The objective of this study was to determine whether raspberry extract (RE) could promote lifespan and stress resistance inCaenorhabditis elegans(C. elegans), and to explore the underlying mechanisms of action. The results showed that the mean lifespan ofC. eleganstreated with RE at 20, 40 and 80 mg mL(-1)was significantly increased by 13.6%, 22.9% and 29.7%, respectively, in a dose-dependent manner. Supplementation with RE decreased the accumulation of lipofuscin and extended the healthspan of animals by improving motility and enhancing resistance to heat stress and UV-B radiation inC. elegans. Meanwhile, treatment with RE could regulate the expression of anti-aging related genes, includingdaf-2,age-1,akt-2,sir-2.1,daf-16,skn-1,jnk-1andhsp-16.2, and promote the migration of DAF-16 into the nucleus. In addition, administration with RE abolished the extension of the lifespan ofdaf-2(e1370)mutants andRNAi(daf-16)C. elegans, and inhibited the expression ofdaf-16downstream genes, includingsod-3,ctl-2,dod17andclk-1. In conclusion, RE could prolong the lifespan, improve the healthspan and enhance stress resistance inC. elegansby the insulin/IGF signaling pathway and DAF-16, providing a theoretical basis to fully exploit raspberry in the prevention of aging and healthcare.