Lonicera japonica extends lifespan and healthspan in Caenorhabditis elegans

Lonicera japonica (LJ) is widely used as the local medicine to improve body and prevent ills in China, but mechanisms of its healthy beneficial effects remain largely unclear. Here, we evaluated the anti-aging and healthspan promoting activities of 75% ethanol extract of LJ (LJ-E) in the animal model Caenorhabditis elegans. Our results showed that LJ-E (500 mu g/mL) treatment enhanced the mean lifespan of worms by over 21.87% and significantly improved age-associated physiological functions in C. elegans. The 500 mu g/mL concentration of LJ-E enhanced the survival rates under oxidative and thermal stresses, and decreased reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies showed that LJ-E-mediated lifespan extension was dependent on mev-1, daf-2, daf-16, and hsf-1, but not eat-2 genes. LJ-E could upregulate stress-inducible genes, viz., hsp16.2, sod-3 and mtl-1. Moreover, we found that the D1086.10 protein interacted with superoxide dismutase (SOD)-3 by functional protein association networks analysis according to RNA-sequencing results. It was confirmed that D1086.10 was needed to promote longevity, and positively regulated expression of sod-3 by using D1086.10 mutants. Furthermore, LJ-E significantly delayed amyloid beta-protein induced paralysis in CL4176 strain. Given the important role of autophagy in aging and protein homeostasis, we observed that LJ-E could remarkably increase the mRNA expression of autophagy gene bec-1 in CL4176 strain, and decrease expression of autophagy substrate p62 protein by more than 40.0% in BC12921 strain. Finally, we found that combination composed of three major compounds (54 mu g/mL chlorogenic acid, 15 mu g/mL 1,5-dicaffeoylquinic acid and 7.5 mu g/mL 1,3-dicaffeoylquinic acid) of 500 mu g/ mL LJ-E could significantly delay paralysis in CL4176 worms caused by A beta toxicity, comparable to that of LJ-E. Overall, our study may have important implications in using Lonicera japonica to promote healthy aging and have a potency to design therapeutics for age-related diseases.