A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia.

Antipsychotic (AP) drugs are used to treat psychiatric disorders but are associated with significant weight gain and metabolic disease. Increased food intake (hyperphagia) appears to be a driving force by which APs induce weight gain but the mechanisms are poorly understood. Here we report that administration of APs to C.

Translation attenuation by minocycline enhances longevity and proteostasis in old post-stress-responsive organisms.

Unlabelled: Aging impairs the activation of stress signaling pathways (SSPs), preventing the induction of longevity mechanisms late in life. Here, we show that the antibiotic minocycline increases lifespan and reduces protein aggregation even in old, SSP-deficient by targeting cytoplasmic ribosomes, preferentially attenuating translation of highly translated mRNAs. In contrast to most other longevity paradigms, minocycline inhibits rather than activates all major SSPs and extends lifespan in mutants deficient in the activation of SSPs, lysosomal or autophagic pathways.

C. elegans as Model for Drug Discovery.

Small molecule screens using C. elegans as a model are becoming increasingly popular as the number of high-throughput methodologies has steadily increased over the years. Here we focus on the biology that underlies this increased popularity and outline the reasons that make C.

Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality.

Longevity mechanisms increase lifespan by counteracting the effects of aging. However, whether longevity mechanisms counteract the effects of aging continually throughout life, or whether they act during specific periods of life, preventing changes that precede mortality is unclear. Here, we uncover transcriptional drift, a phenomenon that describes how aging causes genes within functional groups to change expression in opposing directions.

Atypical antidepressants extend lifespan of Caenorhabditis elegans by activation of a non-cell-autonomous stress response.

Oxidative stress has long been associated with aging and has recently been linked to psychiatric disorders, including psychosis and depression. We identified multiple antipsychotics and antidepressants that extend Caenorhabditis elegans lifespan and protect the animal from oxidative stress. Here, we report that atypical antidepressants activate a neuronal mechanism that regulates the response to oxidative stress throughout the animal.

Measuring Food Intake and Nutrient Absorption in Caenorhabditis elegans.

Caenorhabditis elegans has emerged as a powerful model to study the genetics of feeding, food-related behaviors, and metabolism. Despite the many advantages of C. elegans as a model organism, direct measurement of its bacterial food intake remains challenging.

High-throughput small-molecule screening in Caenorhabditis elegans.

Chemical compounds, which modulate enzymatic activities or those which induce specific phenotypes of interest, are valuable probes to study biological phenomena, as they allow modulation of enzymatic activities and temporal control of protein action. Here, we describe the methodology to conduct large-scale screens for chemical compounds that induce a desired phenotype in the roundworm Caenorhabditis elegans (C. elegans) using 96- or 384-well microtiter plates.

The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR.

Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits.

Quantification of transthyretin kinetic stability in human plasma using subunit exchange.

The transthyretin (TTR) amyloidoses are a group of degenerative diseases caused by TTR aggregation, requiring rate-limiting tetramer dissociation. Kinetic stabilization of TTR, by preferential binding of a drug to the native tetramer over the dissociative transition state, dramatically slows the progression of familial amyloid polyneuropathy. An established method for quantifying the kinetic stability of recombinant TTR tetramers in buffer is subunit exchange, in which tagged TTR homotetramers are added to untagged homotetramers at equal concentrations to measure the rate at which the subunits exchange.

Measuring Caenorhabditis elegans life span in 96 well microtiter plates.

Lifespan is a biological process regulated by several genetic pathways. One strategy to investigate the biology of aging is to study animals that harbor mutations in components of age-regulatory pathways. If these mutations perturb the function of the age-regulatory pathway and therefore alter the lifespan of the entire organism, they provide important mechanistic insights.

Incidence of DVT following surgery of the foot and ankle.

A prospective study was undertaken to establish the incidence of deep vein thrombosis (DVT) in patients who had undergone surgery of the foot and ankle. All consecutive patients who underwent foot and ankle surgery in the senior author's practice had duplex ultrasound performed of the bilateral calves at the first postoperative visit. Of 201 patients, deep calf clots were found in seven patients (3.