Effects of flavonoids on ageing processes in the model organism Caenorhabditis elegans
Final Report Abstract
According to the "free radical theory of aging" an imbalance between generation of reactive oxygen species (ROS) and antioxidative defense mechanisms leads to cumulative damage of macromolecules and thus to impairment of cellular functions and aging. Numerous studies have shown an inverse association between diets rich in fruit and vegetables and the risk for the development of different chronic diseases. Flavonoids and other polyphenolic compounds of plant secondary metabolism are considered to provide health protection and reduce aging processes. Their broad spectrum of biochemical and pharmacological activities is at least partly attributed to their antioxidative properties but the compounds are also known to target various cell-signaling pathways. In C. elegans, a well-established model organism for aging studies, natural plant compounds were shown to increase lifespan and/or the resistance against various stressors. In the present project we analyzed the effects of the three flavonols myricetin, quercetin and kaempferol and the flavanone naringenin on lifespan and stress-resistance of C. elegans and elucidated the underlying mechanisms. To assess bioavailability of the compounds, we established a new and easy-to-use method for detection of flavonoids in vivo in C. elegans. We have shown that flavonols, dependent on the number of hydroxyl-groups attached to their B-ring can increase the lifespan of wild-type C. elegans. This effect is dependent on the flavonol-function (hydroxyl-group and double bond at C-ring) as similar effects could not be obtained in case of naringenin. The lifespan-extending effect proved to be accompanied by a reduction in mitochondrial (mt) ROS levels. Interestingly, only myricetin was also able to increase the lifespan in a C. elegans strain that intrinsically has higher mtROS levels, which is in line with its higher antioxidative potential. Surprisingly, the simultaneously treatment of wild-type C. elegans with myricetin in the presence of a ROS-generating agent shortened the lifespan and reduced survival. Although the reasons for this are not yet understood, it emphasizes how critical the balance between ROS-production and ROS-scavenging systems is in control of longevity and stress-resistance. Alterations of metabolic parameters such as the respiration rate were not associated with the increase in lifespan and were also not affected by the flavonoids. However, all tested flavonoids altered the translocation/distribution (cytosol versus nucleus) of DAF-16 that is a prime downstream target of the insulin/lFG signaling cascade (MS) as well as some of the DAF-16 target genes. It is suggested that these mechanisms contribute, at least partly, to the increase in stress resistance and lifespan effects of the flavonoids.
Publications
-
In vivo visualization of flavonoids in C. elegans using 2-aminoethyl diphenyl borate. Worm Breeders Gazette. June 2010
Grünz, G., Spanier, B. and Daniel, H.
