Quercetin, Caffeic- and Rosmarinic acid exposure extend lifespan in Caenorhabditis elegans. This comparative study uncovers basic common and contrasting underlying mechanisms: For all three compounds, life extension was characterized by hormetic dose response curves, but hsp-level expression was variable. Quercetin and Rosmarinic acid both suppressed bacterial growth; however, antibacterial properties were not the dominant reason for life extension. Exposure to Quercetin, Caffeic- and Rosmarinic acid resulted in reduced body size, altered lipid-metabolism and a tendency towards a delay in reproductive timing; however the total number of offspring was not affected. An indirect dietary restriction effect, provoked by either chemo-repulsion or diminished pharyngeal pumping was rejected. Quercetin and Caffeic acid were shown to increase the antioxidative capacity in vivo and, by means of a lipofuscin assay, reduce the oxidative damage in the nematodes. Finally, it was possible to demonstrate that the life and thermotolerance enhancing properties of Caffeic- and Rosmarinic acid both rely on osr-1, sek-1, sir-2.1 and unc-43 plus daf-16 in the case of Caffeic acid. Taken together, hormesis, in vivo antioxidative/prooxidative properties, modulation of genetic players, as well as the re-allocation of energy all contribute (to some extent and dependent on the polyphenol) to life extension.

The nematode Caenorhabditis elegans responds to flavonoid-rich diets with improved health and longevity. The precise mechanism(s) responsible for this remains to be identified, but is believed to be linked to the highly antioxidative properties of flavonoids. This study provides a dissection of lifespan modulation by the flavonoid quercetin. In detail, quercetin was shown not to act as a simple antimicrobial agent or exclusively via radical scavenging capacities. Likewise, lifespan extension had no effect on reproduction and body length. Furthermore, neither a caloric restriction mimetic nor a sirtuin (sir-2.1) dependence was identified as a likely mode of action. However, four genes were pinpointed to be required for the quercetin derived lifespan extension, namely age-1, daf-2, unc-43 and sek-1. The latter two have, to date, not been linked to quercetin-mediated lifespan extension.

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The model organism Caenorhabditis elegans was utilized to determine, in vivo, the mode(s) of action of four plant polyphenols, namely, tannic acid (TA), gallic acid (GA), ellagic acid (EA), and catechin (CT). The determination of lifespan, stress resistance, growth, reproduction, eating-related behaviors, antioxidative capacities, and lifespan assays with the mev-1 and the eat-2 mutants as well as in the presence of dead bacteria provided new insights into their action. All four compounds prolonged lifespan, but only TA and CT mediated distinct stress protection. Longevity is unlikely the result of antioxidant capacities but rather due to calorie restriction imitating and hormetic properties in the case of TA and EA or antimicrobial capacities of GA and EA. Furthermore, the prominent "disposable soma theory" is only partly reflected by these polyphenols. In summary, this study underlines the diversity of polyphenolic phytochemicals and their mechanistic background.

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