Lysergic acid diethylamide induces behavioral changes in Caenorhabditis elegans.

Lysergic acid diethylamide (LSD) is a synthetic psychedelic compound with potential therapeutic value for psychiatric disorders. This study aims to establish Caenorhabditis elegans as an in vivo model for examining LSD's effects on locomotor behavior. Our results demonstrate that LSD is absorbed by C.

Parental age effect on the longevity and healthspan in and .

Several studies have investigated the effect of parental age on biological parameters such as reproduction, lifespan, and health; however, the results have been inconclusive, largely due to inter-species variation and/or modest effect sizes. Here, we examined the effect of parental age on the lifespan, reproductive capacity, and locomotor activity of genetic isogenic lines of the nematode and the fruit fly . We found that the progeny of successive generations of old parents had significantly shorter lifespans than the progeny of young parents in both species.

Comparison of lipidome profiles of Caenorhabditis elegans-results from an inter-laboratory ring trial.

Introduction: Lipidomic profiling allows 100s if not 1000s of lipids in a sample to be detected and quantified. Modern lipidomics techniques are ultra-sensitive assays that enable the discovery of novel biomarkers in a variety of fields and provide new insight in mechanistic investigations. Despite much progress in lipidomics, there remains, as for all high throughput "omics" strategies, the need to develop strategies to standardize and integrate quality control into studies in order to enhance robustness, reproducibility, and usability of studies within specific fields and beyond.

Lifespan-extending interventions enhance lipid-supported mitochondrial respiration in Caenorhabditis elegans.

Dietary restriction and reduced reproduction have been linked to long lifespans in the vast majority of species tested. Although decreased mitochondrial mass and/or function are hallmarks of aging, little is known about the mechanisms by which these organelles contribute to physiological aging or to the effects of lifespan-extending interventions, particularly with respect to oxidative phosphorylation and energy production. Here, we employed the nematode Caenorhabditis elegans to examine the effects of inhibition of germline proliferation and dietary restriction, both of which extend the lifespan of C.

Lipase-like 5 enzyme controls mitochondrial activity in response to starvation in Caenorhabditis elegans.

The C. elegans lipase-like 5 (lipl-5) gene is predicted to code for a lipase homologous to the human gastric acid lipase. Its expression was previously shown to be modulated by nutritional or immune cues, but nothing is known about its impact on the lipid landscape and ensuing functional consequences.

Coelomocytes Regulate Starvation-Induced Fat Catabolism and Lifespan Extension through the Lipase LIPL-5 in Caenorhabditis elegans.

Dietary restriction is known to extend the lifespan and reduce fat stores in most species tested to date, but the molecular mechanisms linking these events remain unclear. Here, we found that bacterial deprivation of Caenorhabditis elegans leads to lifespan extension with concomitant mobilization of fat stores. We find that LIPL-5 expression is induced by starvation and that the LIPL-5 lipase is present in coelomocyte cells and regulates fat catabolism and longevity during the bacterial deprivation response.

The transcription factor NHR-8: A new target to increase ivermectin efficacy in nematodes.

Resistance to the anthelmintic macrocyclic lactone ivermectin (IVM) has a great impact on the control of parasitic nematodes. The mechanisms by which nematodes adapt to IVM remain to be deciphered. We have identified NHR-8, a nuclear hormone receptor involved in the xenobiotic response in Caenorhabditis elegans, as a new regulator of tolerance to IVM.

A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response.

Plant extracts containing salicylates are probably the most ancient remedies to reduce fever and ease aches of all kind. Recently, it has been shown that salicylates activate adenosine monophosphate-activated kinase (AMPK), which is now considered as a promising target to slow down aging and prevent age-related diseases in humans. Beneficial effects of AMPK activation on lifespan have been discovered in the model organism Caenorhabditis elegans (C.

HIF-1-dependent regulation of lifespan in by the acyl-CoA-binding protein MAA-1.

In yeast, the broadly conserved acyl-CoA-binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically inactivated each of the seven ACBP paralogs and found that one of them, (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity.

Two phases of aging separated by the Smurf transition as a public path to death.

Aging's most obvious characteristic is the time dependent increase of an individual's probability to die. This lifelong process is accompanied by a large number of molecular and physiological changes. Although numerous genes involved in aging have been identified in the past decades its leading factors have yet to be determined.

The Role of Dafachronic Acid Signaling in Development and Longevity in Caenorhabditis elegans: Digging Deeper Using Cutting-Edge Analytical Chemistry.

Steroid hormones regulate physiological processes in species ranging from plants to humans. A wide range of steroid hormones exist, and their contributions to processes, such as growth, reproduction, development, and aging, is almost always complex. Understanding the biosynthetic pathways that generate steroid hormones and the signaling pathways that mediate their effects is thus of fundamental importance.

The mysterious relationship between reproduction and longevity.

A negative correlation between fertility and longevity has been documented in many species under a variety of conditions, but the association is not always observed,(1) leading to heated discussion about the nature of the reproduction-longevity relationship.(2) This debate is further fueled by the fact that no genes or molecules have been clearly shown to link the 2 traits. A recent study by Thondamal et al.

Fast separation and quantification of steroid hormones Δ4- and Δ7-dafachronic acid in Caenorhabditis elegans.

Separation of isomeric molecular species, e.g. double bond position isomers, is a challenging task for liquid chromatography.

Steroid hormone signalling links reproduction to lifespan in dietary-restricted Caenorhabditis elegans.

Dietary restriction (DR) increases healthspan and longevity in many species, including primates, but it is often accompanied by impaired reproductive function. Whether signals associated with the reproductive system contribute to or are required for DR effects on lifespan has not been established. Here we show that expression of the cytochrome P450 DAF-9/CYP450 and production of the steroid hormone Δ(7)-dafachronic acid (DA) are increased in C.

Aging yeast cells undergo a sharp entry into senescence unrelated to the loss of mitochondrial membrane potential.

In budding yeast, a mother cell can produce a finite number of daughter cells before it stops dividing and dies. Such entry into senescence is thought to result from a progressive decline in physiological function, including a loss of mitochondrial membrane potential (ΔΨ). Here, we developed a microfluidic device to monitor the dynamics of cell division and ΔΨ in real time at single-cell resolution.

Reproduction, fat metabolism, and life span: what is the connection?

Reduced reproduction is associated with increased fat storage and prolonged life span in multiple organisms, but the underlying regulatory mechanisms remain poorly understood. Recent studies in several species provide evidence that reproduction, fat metabolism, and longevity are directly coupled. For instance, germline removal in the nematode Caenorhabditis elegans promotes longevity in part by modulating lipid metabolism through effects on fatty acid desaturation, lipolysis, and autophagy.

Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans.

Background: Preventing germline stem cell proliferation extends lifespan in nematodes and flies. So far, studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR. Here, we report on NHR-80/HNF4, a nuclear receptor that specifically mediates longevity induced by depletion of the germ line through a mechanism that implicates fatty acid monodesaturation.

Carbonylated proteins are eliminated during reproduction in C. elegans.

Oxidatively damaged proteins accumulate with age in many species (Stadtman (1992) Science257, 1220-1224). This means that damage must be reset at the time of reproduction. To visualize this resetting in the roundworm Caenorhabditis elegans, a novel immunofluorescence technique that allows the detection of carbonylated proteins in situ was developed.

PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans.

Reduced food intake as a result of dietary restriction increases the lifespan of a wide variety of metazoans and delays the onset of multiple age-related pathologies. Dietary restriction elicits a genetically programmed response to nutrient availability that cannot be explained by a simple reduction in metabolism or slower growth of the organism. In the nematode worm Caenorhabditis elegans, the transcription factor PHA-4 has an essential role in the embryonic development of the foregut and is orthologous to genes encoding the mammalian family of Foxa transcription factors, Foxa1, Foxa2 and Foxa3.

Elimination of damaged proteins during differentiation of embryonic stem cells.

During mammalian aging, cellular proteins become increasingly damaged: for example, by carbonylation and formation of advanced glycation end products (AGEs). The means to ensure that offspring are born without such damage are unknown. Unexpectedly, we found that undifferentiated mouse ES cells contain high levels of both carbonyls and AGEs.

Organization and regulation of the cytosolic NADH metabolism in the yeast Saccharomyces cerevisiae.

Keeping a cytosolic redox balance is a prerequisite for living cells in order to maintain a metabolic activity and enable growth. During growth of Saccharomyces cerevisiae, an excess of NADH is generated in the cytosol. Aerobically, it has been shown that the external NADH dehydrogenase, Nde1p and Nde2p, as well as the glycerol-3-phosphate dehydrogenase shuttle, comprising the cytoplasmic glycerol-3-phosphate dehydrogenase, Gpdlp, and the mitochondrial glycerol-3-phosphate dehydrogenase, Gut2p, are the most important mechanisms for mitochondrial oxidation of cytosolic NADH.

The oncogenic RAS2(val19) mutation locks respiration, independently of PKA, in a mode prone to generate ROS.

The RAS2(val19) allele, which renders the cAMP-PKA pathway constitutively active and decreases the replicative life-span of yeast cells, is demonstrated to increase production of reactive oxygen species (ROS) and to elevate oxidative protein damage. Mitochondrial respiration in the mutant is locked in a non-phosphorylating mode prone to generate ROS but this phenotype is not linked to a constitutively active PKA pathway. In contrast, providing RAS2(val19) cells with the mammalian uncoupling protein UCP1 restores phosphorylating respiration and reduces ROS levels, but does not correct for PKA-dependent defects.

NADH is specifically channeled through the mitochondrial porin channel in Saccharomyces cerevisiae.

In many kinds of permeabilized cells, the restriction of metabolite diffusion by a mitochondrial porin "closed state" has been shown to control the respiration rate. However, since in isolated mitochondria the porin appears to be always "open," the physiological relevance of a putative regulation via this channel status is now a subject of discussion. In Saccharomyces cerevisiae, in which some of the NADH dehydrogenase active sites are facing the intermembrane space, this regulatory mechanism might play an important role for the regulation of the cytosolic redox status.