Jasonia glutinosa (L.) DC., a Traditional Herbal Tea, Exerts Antioxidant and Neuroprotective Properties in Different In Vitro and In Vivo Systems.

In traditional medicine, Jasonia glutinosa (L.) DC or rock tea (RT) has been mainly used to treat digestive and respiratory pathologies but also as an antimicrobial or an antidepressant herbal remedy. An ethanolic extract of RT has been demonstrated to have antioxidant and anti-inflammatory effects, which may be explained by its phytochemical profile, rich in polyphenols and pigments. The aim of this study is to investigate the neuroprotective potential of RT. For this purpose, the ethanolic extract of RT is assayed in Caenorhabditis elegans (C. elegans) as an in vivo model, and through in vitro assays using monoamine oxidase A, tyrosinase and acetylcholinesterase as enzymes. The RT extract reduces juglone-induced oxidative stress in worms and increases the lifespan and prevents paralysis of C. elegans CL4176, a model of Alzheimer's disease; the extract is also able to inhibit enzymes such as acetylcholinesterase, monoamine oxidase A and tyrosinase in vitro. Together these results demonstrate that Jasonia glutinosa is a good candidate with antioxidant and neuroprotective potential for the development of new products with pharmaceutical interests.

Antioxidant and Antiaging Effects of Licorice on the Caenorhabditis elegans Model.

The causative relationship between oxidative stress and aging remains controversial, but it is a fact that many of the pathologies of age-related diseases are associated with oxidative stress. Phytochemicals may reduce damage from oxidative stress; the intake of these through diet could represent a strategy to lessen their pathological consequences. The popular and widely consumed licorice (Glycyrrhiza glabra) is a rich source of potential antioxidants. The aim of this study was to investigate whether licorice increases the oxidative stress resistance and lifespan of the animal model Caenorhabditis elegans. Licorice roots ethanolic extract showed in vitro antioxidant activity, with an IC50 of 51.17 µg/mL using 2,2-diphenyl-1-picrylhydrazyl (DPPH) as free radical. C. elegans pretreated with licorice showed an increase of survival rate when exposed to the oxidant juglone, being this increase up to ∼33.56%. This pretreated population also showed an increase in lifespan of 14.28% at a concentration of 250 µg/mL. In conclusion, we suggest that licorice has a high antioxidant capability both in vitro and in vivo and that this activity may explain the observed extension of lifespan.

Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy.

While the majority of phosphatidylinositol-4, 5-bisphosphate (PI-4, 5-P2) in mammalian cells is generated by the conversion of phosphatidylinositol-4-phosphate (PI-4-P) to PI-4, 5-P2, a small fraction can be made by phosphorylating phosphatidylinositol-5-phosphate (PI-5-P). The physiological relevance of this second pathway is not clear. Here, we show that deletion of the genes encoding the two most active enzymes in this pathway, Pip4k2a and Pip4k2b, in the liver of mice causes a large enrichment in lipid droplets and in autophagic vesicles during fasting. These changes are due to a defect in the clearance of autophagosomes that halts autophagy and reduces the supply of nutrients salvaged through this pathway. Similar defects in autophagy are seen in nutrient-starved Pip4k2a-/-Pip4k2b-/- mouse embryonic fibroblasts and in C. elegans lacking the PI5P4K ortholog. These results suggest that this alternative pathway for PI-4, 5-P2 synthesis evolved, in part, to enhance the ability of multicellular organisms to survive starvation.

Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.

Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging.

Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism.

The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional and pathogenic effects on its nematode predator/host that impact health and aging. We report that metformin increases lifespan by altering microbial folate and methionine metabolism. Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic. Metformin increases or decreases worm lifespan, depending on E. coli strain metformin sensitivity and glucose concentration. In mammals, the intestinal microbiome influences host metabolism, including development of metabolic disease. Thus, metformin-induced alteration of microbial metabolism could contribute to therapeutic efficacy-and also to its side effects, which include folate deficiency and gastrointestinal upset.

Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans.

It was recently reported that the plant polyphenol resveratrol, found, e.g., in grape berry skins, extended lifespan in the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. This lifespan extension was dependent on an NAD(+)-dependent histone deacetylase, Sir2 in Drosophila and SIR-2.1 in C. elegans. The extension of lifespan appeared to occur through a mechanism related to dietary restriction (DR), the reduction of available nutrients without causing malnutrition, an intervention that extends lifespan in diverse organisms from yeast to mammals. In Drosophila, lifespan extension by DR is associated with a reduction in fecundity. However, a slight increase in fecundity was reported upon treatment with resveratrol, suggesting a mode of action at least partially distinct from that of DR. To probe this mechanism further, we initiated a new study of the effects of resveratrol on Drosophila. We saw no significant effects on lifespan in seven independent trials. We analysed our resveratrol and found that its structure was normal, with no oxidative modifications. We therefore re-tested the effects of resveratrol in C. elegans, in both wild-type and sir-2.1 mutant worms. The results were variable, with resveratrol treatment resulting in slight increases in lifespan in some trials but not others, in both wild type and sir-2.1 mutant animals. We postulate that the effect of resveratrol upon lifespan in C. elegans could reflect induction of phase 2 drug detoxification or activation of AMP kinase.