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

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 in Caenorhabditis elegans (C. elegans), and to explore the underlying mechanisms of action. The results showed that the mean lifespan of C. elegans treated 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(definition) of animals by improving motility and enhancing resistance to heat stress and UV-B radiation in C. elegans. Meanwhile, treatment with RE could regulate the expression of anti-aging related genes, including daf-2, age-1, akt-2, sir-2.1, daf-16, skn-1, jnk-1 and hsp-16.2, and promote the migration of DAF-16 into the nucleus. In addition, administration with RE abolished the extension of the lifespan of daf-2(e1370) mutants and RNAi (daf-16) C. elegans, and inhibited the expression of daf-16 downstream genes, including sod-3, ctl-2, dod17 and clk-1. In conclusion, RE could prolong the lifespan, improve the healthspan and enhance stress resistance in C. elegans by the insulin/IGF signaling pathway and DAF-16, providing a theoretical basis to fully exploit raspberry in the prevention of aging and healthcare.