Structural features and bioavailability of four flavonoids and their implications for lifespan-extending and antioxidant actions in C. elegans.

Various studies have demonstrated longevity effects of flavonoids, a major sub-group of plant polyphenolic compounds, in Caenorhabditis elegans. To better understand their structure-activity relationship in vivo we have used a comparative approach by exposing C. elegans to the structurally related flavonoids myricetin, quercetin, kaempferol and naringenin, and assessed their impact on lifespan and on putative modes of action. The bioavailability of the tested flavonoids was demonstrated by high-performance liquid chromatography with diode-array detection (HPLC/DAD) and a 2-aminoethyl diphenyl borate-based in vivo approach. While all flavonols increased lifespan in wild-type, only myricetin elongated the mev-1(kn1) lifespan, suggesting that the flavonols antioxidant action alone is not sufficient for longevity. Structural prerequisites of high antioxidant action in vitro were also essential to reduce the reactive oxygen species (ROS) load in vivo in C. elegans and were tested in isolated mouse muscle mitochondria. Since the insulin/IGF-like signaling (IIS) cascade is a key regulator of lifespan, all compounds were tested for the ability to cause nuclear translocation of the FOXO transcription factor DAF-16 and changes in target gene expression. An increased DAF-16 translocation and sod-3 promoter activity were observed with all flavonoids but was independent of their ROS scavenging capability and their effects on lifespan.

Grünz G ，Haas K ，Soukup S ，Klingenspor M ，Kulling SE ，Daniel H ，Spanier B ... -  《-》

Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans.

Kampkötter A ，Gombitang Nkwonkam C ，Zurawski RF ，Timpel C ，Chovolou Y ，Wätjen W ，Kahl R ... -  《ARCHIVES OF TOXICOLOGY》

Redox regulation, gene expression and longevity.

Honda Y ，Tanaka M ，Honda S 《-》

Curcumin-mediated lifespan extension in Caenorhabditis elegans.

Curcumin is the active ingredient in the herbal medicine and dietary spice, turmeric (Curcuma longa). It has a wide range of biological activities, including anti-inflammatory, antioxidant, chemopreventive, and chemotherapeutic activities. We examined the effects of curcumin on the lifespan and aging in Caenorhabditis elegans, and found that it responded to curcumin with an increased lifespan and reduced intracellular reactive oxygen species and lipofuscin during aging. We analyzed factors that might influence lifespan extension by curcumin. We showed that lifespan extension by curcumin in C. elegans is attributed to its antioxidative properties but not its antimicrobial properties. Moreover, we showed that lifespan extension had effects on body size and the pharyngeal pumping rate but not on reproduction. Finally, lifespan tests with selected stress- and lifespan-relevant mutant strains revealed that the lifespan-extending phenotype was absent from the osr-1, sek-1, mek-1, skn-1, unc-43, sir-2.1, and age-1 mutants, whereas curcumin treatment prolonged the lifespan of mev-1 and daf-16 mutants. Our study has unraveled a diversity of modes of action and signaling pathways to longevity and aging with curcumin exposure in vivo.

Liao VH ，Yu CW ，Chu YJ ，Li WH ，Hsieh YC ，Wang TT ... -  《-》

Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin.

Kampkötter A ，Timpel C ，Zurawski RF ，Ruhl S ，Chovolou Y ，Proksch P ，Wätjen W ... -  《COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY》