Lamotrigine extends lifespan but compromises health span in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds.     

The longevity effect of cranberry extract in Caenorhabditis elegans is modulated by daf-16 and osr-1

Nutraceuticals are known to have numerous health and disease preventing properties. Recent studies suggest that extracts containing cranberry may have anti-aging benefits. However, little is known about whether and how cranberry by itself promotes longevity and healthspan in any organism. Here we examined the effect of a cranberry only extract on lifespan and healthspan in Caenorhabditis elegans. Supplementation of the diet with cranberry extract (CBE) increased the lifespan in C. elegans in a concentration-dependent manner. Cranberry also increased tolerance of C. elegans to heat shock, but not to oxidative stress or ultraviolet irradiation. In addition, we tested the effect of cranberry on brood size and motility and found that cranberry did not influence these behaviors. Our mechanistic studies indicated that lifespan extension induced by CBE requires the insulin/IGF signaling pathway and DAF-16. We also found that cranberry promotes longevity through osmotic stress resistant-1 (OSR-1) and one of its downstream effectors, UNC-43, but not through SEK-1, a component of the p38 MAP kinase pathway. However, SIR-2.1 and JNK signaling pathways are not required for cranberry to promote longevity. Our findings suggest that cranberry supplementation confers increased longevity and stress resistance in C. elegans through pathways modulated by daf-16 and osr-1. This study reveals the anti-aging property of widely consumed cranberry and elucidates the underpinning mechanisms.     

The Imaginal Disc Growth Factors 2 and 3 participate in the Drosophila response to nematode infection

The Drosophila imaginal disc growth factors (IDGFs) induce the proliferation of imaginal disc cells and terminate cell proliferation at the end of larval development. However, the participation of Idgf‐encoding genes in other physiological processes of Drosophila including the immune response to infection is not fully understood. Here, we show the contribution of Idgf2 and Idgf3 in the Drosophila response to infection with Steinernema carpocapsae nematodes carrying or lacking their mutualistic Xenorhabdus nematophila bacteria (symbiotic or axenic nematodes, respectively). We find that Idgf2 and Idgf3 are upregulated in Drosophila larvae infected with symbiotic or axenic Steinernema and inactivation of Idgf2 confers a survival advantage to Drosophila larvae against axenic nematodes. Inactivation of Idgf2 induces the Imd and Jak/Stat pathways, whereas inactivation of Idgf3 induces the Imd, Toll and Jak/Stat pathways. We also show that inactivation of the Imd pathway receptor PGRP‐LE upregulates Idgf2 against Steinernema nematode infection. Finally, we demonstrate that inactivation of Idgf3 induces the recruitment of larval haemocytes in response to Steinernema. Our results indicate that Idgf2 and Idgf3 might be involved in different yet crucial immune functions in the Drosophila antinematode immune response. Similar findings will promote the development of new targets for species‐specific pest control strategies.     

Knock-down of REL2, but not defensin A, augments Aedes aegypti susceptibility to Bacillus subtilis and Escherichia coli

Some components of the Toll and Imd immune signaling pathways have remained conserved between Drosophila and mosquitoes, however, important differences in the way invading microorganisms activate these pathways in these organisms have started to be revealed. In the present study, we have attempted to silence the Aedes aegypti NF-κB-like factor REL2, which is analogous to Drosophila Relish, and analyze the effects on mosquito mortality upon infection with a Gram-negative and a Gram-positive bacterium, both containing a DAP-type peptidoglycan, and effects on embryo development. Moreover, we have silenced one of the antimicrobial peptides (AMPs) controlled by REL2, defensin A, a major AMP in A. aegypti, and compared the results on mosquito mortality upon bacterial infection to those obtained with REL2 silencing. Results show that REL2 is crucial for A. aegypti immunity upon infection with Escherichia coli and Bacillus subtilis, corroborating with previous studies on that REL2/Imd in mosquitoes is involved in a generalized antibacterial defense, differently than its analogous in Drosophila. However, defensin A silencing did not cause a significant increase in mortality in infected mosquitoes, indicating that this peptide is not essential in mosquito protection against the two bacteria and that other immune factors controlled by REL2 are playing this role. In regard to embryo development, REL2 knock-down did not cause any significant effect on: the number of laid eggs, number of developed pupae, percent of emerged adults, and ratio between emerged females versus males. A slight decrease in the number of hatched eggs (percent eclosion) was observed in REL2 knock-down mosquitoes, but these observations were inconclusive.     

Systems analysis of the single photon response in invertebrate photoreceptors

Photoreceptors of Drosophila compound eye employ a G protein-mediated signaling pathway that transduces single photons into transient electrical responses called “quantum bumps” (QB). Although most of the molecular components of this pathway are already known, the system-level understanding of the mechanism of QB generation has remained elusive. Here, we present a quantitative model explaining how QBs emerge from stochastic nonlinear dynamics of the signaling cascade. The model shows that the cascade acts as an “integrate and fire” device and explains how photoreceptors achieve reliable responses to light although keeping low background in the dark. The model predicts the nontrivial behavior of mutants that enhance or suppress signaling and explains the dependence on external calcium, which controls feedback regulation. The results provide insight into physiological questions such as single-photon response efficiency and the adaptation of response to high incident-light level. The system-level analysis enabled by modeling phototransduction provides a foundation for understanding G protein signaling pathways less amenable to quantitative approaches.     

Regulation of Drosophila lifespan by JNK signaling

Cellular responses to extrinsic and intrinsic insults have to be carefully regulated to properly coordinate cytoprotection, repair processes, cell proliferation and apoptosis. Stress signaling pathways, most prominently the Jun-N-terminal Kinase (JNK) pathway, are critical regulators of such cellular responses and have accordingly been implicated in the regulation of lifespan in various organisms. JNK signaling promotes cytoprotective gene expression, but also interacts with the insulin signaling pathway to influence growth, metabolism, stress tolerance and regeneration. Here, we review recent studies in Drosophila that elucidate the tissue-specific and systemic consequences of JNK activation that ultimately impact lifespan of the organism.     

Effect of ginseng on the life span of Drosophila

Feeding ginseng (Panax ginseng) to Drosophila for their entire adult life span at 0.25 mg/ml gave no significant change in life span. At higher concentrations of 2.5 and 25.0 mg/ml the median life span was reduced by 6.4 and 10.6%. Our results confirm a previous study with mice (Bittles, et al.) and refute the widely held belief that ginseng has anti-aging properties.