Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C. elegans) as a model for the assessment of pharmacological and toxicological parameters following exposure to two 4-phenylchalcogenil-7-chloroquinolines derivatives (PSQ for selenium and PTQ for tellurium-containing compounds). While non-lethal concentrations (NLC) of PTQ and PSQ attenuated paraquat-induced effects on survival, lifespan and oxidative stress parameters, lethal concentrations (LC) of PTQ and PSQ alone are able to impair these parameters in C. elegans. We also demonstrate that DAF-16/FOXO and SKN-1/Nrf2 transcription factors underlie the mechanism of action of these compounds, as their targets sod-3, gst-4 and gcs-1 were modulated following exposures in a daf-16- and skn-1-dependent manner. Finally, in accordance with a disturbed thiol metabolism in both LC and NLC, we found higher sensitivity of trxr-1 worm mutants (lacking the selenoprotein thioredoxin reductase 1) when exposed to PSQ. Finally, our study suggests new targets for the investigation of organochalcogen pharmacological effects, reinforcing the use of C. elegans as a powerful platform for preclinical approaches.

Recent studies have shown that phenolic compounds present in yerba mate have antioxidant defense properties. To verify whether Ilex paraguariensis extracts are capable of increasing the lifespan of an organism, we have used the free-living nematode Caenorhabditis elegans. Notably, this is the first study that analyzes the effects of the extracts of yerba mate obtained from an extraction method that mimics the manner that the plant is consumed by the population by using a live organism. Yerba mate was purchased from commercial markets from Argentina, Brazil, and Uruguay. Ilex paraguariensis extracts significantly increased the life span of C. elegans. Moreover, the extracts reduced the ROS levels per se, and protected from the reduced survival and reproduction rate induced by paraquat exposure. Considering molecular aspects, we observed that the worms pretreated with the extracts depicted higher translocation of the transcription factor DAF-16::GFP to the nucleus. However, there was no increase in the levels of the DAF-16 target genes, SOD-3 and catalase. Our results suggest that the increase of lifespan caused by the different extracts is associated to the antioxidant potential of yerba mate, however this effect is not completely mediated by daf-16.

ObjectiveDietary restriction (DR) improves health and prolongs lifespan in part by upregulating type III endoribonuclease DICER in adipose tissue. In this study, we aimed to specifically test which missing dietary component was responsible for DICER upregulation.MethodsWe performed a nutrient screen in mouse preadipocytes and validated the results in vivo using different kinds of dietary interventions in wild type or genetically modified mice and worms, also testing the requirement of DICER on the effects of the diets.ResultsWe found that sulfur amino acid restriction (i.e., methionine or cysteine) is sufficient to increase Dicer mRNA expression in preadipocytes. Consistently, while DR increases DICER expression in adipose tissue of mice, this effect is blunted by supplementation of the diet with methionine, cysteine, or casein, but not with a lipid or carbohydrate source. Accordingly, dietary methionine or protein restriction mirrors the effects of DR. These changes are associated with alterations in serum adiponectin. We also found that DICER controls and is controlled by adiponectin. In mice, DICER plays a role in methionine restriction-induced upregulation of Ucp1 in adipose tissue. In C. elegans, DR and a model of methionine restriction also promote DICER expression in the intestine (an analog of the adipose tissue) and prolong lifespan in a DICER-dependent manner.ConclusionsWe propose an evolutionary conserved mechanism in which dietary sulfur amino acid restriction upregulates DICER levels in adipose tissue leading to beneficial health effects.

Iron (Fe) exposure, results in multiple biological defects in C. elegans, including reproductive and motor impairment, which may be related to oxidative stress and neuronal damage.

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