Caenorhabditis elegans is an instrumental research model used to advance our knowledge in areas including development, metabolism, and aging. However, research on metabolism and/or other measures of health/aging are confounded by the nematode’s food source in the lab, live E. coli bacteria. Commonly used treatments, including ultraviolet irradiation and antibiotics, are successful in preventing bacterial replication, but the bacteria can remain metabolically active. The purpose of this study is to develop a metabolically inactive food source for the worms that will allow us to minimize the confounding effects of bacterial metabolism on worm metabolism and aging. Our strategy is to use a paraformaldehyde (PFA) treated E. coli food source and to determine its effects on worm health, metabolism and longevity. We initially determine the lowest possible concentrations of PFA necessary to rapidly and reproducibly kill bacteria. We then measure various aspects of worm behavior, healthspan and longevity, including growth rate, food attraction, brood size, lifespan and metabolic assessments, such as oxygen consumption and metabolomics. Our resulting data show that worms eat and grow well on these bacteria and support the use of 0.5% PFA-killed bacteria as a nematode food source for metabolic, drug, and longevity experiments.
An organism’s ability to perceive and respond to changes in its environment is crucial for its health and survival. Here we reveal how the most well-studied longevity intervention, dietary restriction, acts in-part through a cell non-autonomous signaling pathway that is inhibited by the presence of attractive smells. Using an intestinal reporter for a key gene induced by dietary restriction but suppressed by attractive smells, we identify three compounds that block food odor effects in C. elegans, thereby increasing longevity as dietary restriction mimetics. These compounds clearly implicate serotonin and dopamine in limiting lifespan in response to food odor. We further identify a chemosensory neuron that likely perceives food odor, an enteric neuron that signals through the serotonin receptor 5-HT1A/SER-4, and a dopaminergic neuron that signals through the dopamine receptor DRD2/DOP-3. Aspects of this pathway are conserved in D. melanogaster. Thus, blocking food odor signaling through antagonism of serotonin or dopamine receptors is a plausible approach to mimic the benefits of dietary restriction.
Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans, fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). These changes are likely relevant, as we find that genetically modifying OCM enzyme expression leads to alterations in longevity that interact with fmo-2 expression. Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO-2. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and important role in promoting health and longevity through metabolic remodeling.
love writing!" exclaimed Sarah as she put the finishing touches on her verb poster. All of the third graders in this class were busy working on their parts-of-speech posters during an interactive writing lesson. These are the words that all teachers desire to hear from their students. Who knew that Sarah, a struggling writer at the beginning of the school year, would ever utter such a positive statement about writing? "Interactive writing provides powerful demonstrations of writing that help young children make progress in their own writing" (McCarrier, Pinnell, & Fountas, 2000, p. xvi).Interactive writing can take on many different forms and is used in a variety of ways in the classroom. This type of writing helps build a bridge between writing and all other areas of the curriculum. In this process, students and teachers collaborate in the construction of text while building on prior knowledge. Students use what they know about language, conventions of print, and how words work to create meaningful writing. English-language learners (ELLs) especially benefit from collaborating with their peers when writing and revising (Hudelson, 1988). When ELLs interact socially and linguistically they develop greater language proficiency (Long, 1983).Attitude, motivation, and engagement are vital factors that contribute to reading and writing success. According to Partin and Hendricks (2002), reading achievement is related to a positive attitude toward reading. A primary concern of many teachers is that a lack of engagement is the root of the many problems they face in teaching (Edmunds & Bauserman, 2006). The teacher generating high expectations for reading and writing while providing time to share and discuss can expect a higher level of literacy engagement in students.Interactive writing can be a valuable instructional method that greatly enhances engagement in the classroom. This technique improves spelling knowledge, provides a letter-sound connection, and links the decoding process to writing. It reaches all students and ability levels by developing language and building schema. Classroom reading materials are created by children's language and experiences, which help to il-lustrate the connection between written and oral language (Rubadue, 2002). In particular, this is helpful when working with ELLs because it provides a purposeful writing task in a comfortable environment. As stated by Hudelson (1988), the classroom environment can notably stimulate ELLs' development as writers. Our Thoughts on Interactive WritingAs elementary school teachers in three different California schools, we each use interactive writing in our classrooms on a regular basis. This is not another mandated program but rather an easy-to-use technique we implement to enhance our curriculum. Not only does it engage our students, but it also improves their language development, writing, and spelling skills. In regard to ELLs, we have observed an increase in vocabulary, grammar, and writing skills as well as an increase in confidence from the continu...
BackgroundDiet-mediated alterations of critical brain nutrient transporters, major facilitator super family domain-containing 2a (Mfsd2a) and glucose transporter 1 (Glut1), have wide reaching implications in brain health and disease.ObjectiveThe aim of the study was to examine the impact of long-term low- and high-fat diets with lard or fish oil on critical brain nutrient transporters, Mfsd2a and Glut1.MethodsEight-week-old male C57BL/6 mice were fed 1 of the following 4 diets for 32 wk: 10% of kcal from lard, 10% of kcal from fish oil, 41% of kcal from lard, or 41% of kcal from fish oil. Body weight and blood chemistries delineated dietary effects. Cortical and subcortical Mfsd2a and Glut1 mRNA and protein expression were evaluated, with other supportive nutrient-sensitive targets also assessed for mRNA expression changes.ResultsFish-oil diets increased cortical Mfsd2a mRNA expression compared with lard diets. Subcortical Mfsd2a mRNA expression decreased as the percentage of fat in the diet increased. There was an interaction between the type and percentage of fat with cortical and subcortical Mfsd2a and cortical Glut1 protein expression. In the lard diet groups, protein expression of cortical and subcortical Mfsd2a and cortical Glut1 significantly increased as fat percentage increased. As the fat percentage increased in the fish-oil diet groups, protein expression of cortical and subcortical Mfsd2a and cortical Glut1 did not change. When comparing the fish-oil groups with 10% lard, cortical Mfsd2a protein expression was significantly higher in the 10% and 41% fish-oil groups, whereas cortical Glut1 protein expression was significantly higher in only the 10% fish-oil group. A positive correlation between cortical peroxisome proliferator–activated receptor γ mRNA expression and Mfsd2a protein expression was shown.ConclusionCorresponding to chronic dietary treatment, an interaction between the type of fat and the percentage of fat exists respective to changes in brain expression of the key nutrient transporters Mfsd2a and Glut1.
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