Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan

Author: Berry, Brandon J.; Vodickova, Anezka; Muller-Eigner, Annika; Meng, Chen; Ludwig, Christina; Kaeberlein, Matt; Peleg, Shahaf; Wojtovich, Andrew P. Description: Mitochondrial dysfunction plays a central role in aging but the exact biological causes are still being determined. Here, we show that optogenetically increasing mitochondrial membrane potential during adulthood using a light-activated proton pump improves age-associated phenotypes and extends lifespan in C. elegans. Our findings provide direct causal evidence that rescuing the age-related decline in mitochondrial membrane potential is sufficient to slow the rate of aging and extend healthspan and lifespan….

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Homeostatic Responses Regulate Selfish Mitochondrial Genome Dynamics in C. elegans

Author: Gitschlag, Bryan L.; Kirby, Cait S.; Samuels, David C.; Gangula, Rama D.; Mallal, Simon A.; Patel, Maulik R. Description: Mutant mitochondrial genomes (mtDNA) can be viewed as selfish genetic elements that persist in a state of heteroplasmy despite having potentially deleterious metabolic consequences. We sought to study regulation of selfish mtDNA dynamics. We establish that the large 3.1-kb deletion-bearing mtDNA variant uaDf5 is a selfish genome in Caenorhabditis elegans. Next, we show that uaDf5 mutant mtDNA replicates in addition to, not at the expense of, wild-type mtDNA. These data…

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Functional genomic analysis of C. elegans chromosome I by systematic RNA interference

Author: Fraser, A. G.; Kamath, R. S.; Zipperlen, P.; Martinez-Campos, M.; Sohrmann, M.; Ahringer, J. Description: Complete genomic sequence is known for two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and it will soon be known for humans. However, biological function has been assigned to only a small proportion of the predicted genes in any animal. Here we have used RNA-mediated interference (RNAi) to target nearly 90% of predicted genes on C. elegans chromosome I by feeding worms with bacteria that express double-stranded RNA. We…

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Inducible systemic RNA silencing in Caenorhabditis elegans

Author: Timmons, Lisa; Tabara, Hiroaki; Mello, Craig C.; Fire, Andrew Z. Description: Introduction of double-stranded RNA (dsRNA) can elicit a gene-specific RNA interference response in a variety of organisms and cell types. In many cases, this response has a systemic character in that silencing of gene expression is observed in cells distal from the site of dsRNA delivery. The molecular mechanisms underlying the mobile nature of RNA silencing are unknown. For example, although cellular entry of dsRNA is possible, cellular exit of dsRNA from normal animal cells has not been…

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Genetic control of programmed cell death in the nematode C. elegans

Author: Ellis, H. M.; Horvitz, H. R. Description: The wild-type functions of the genes ced-3 and ced-4 are required for the initiation of programmed cell deaths in the nematode Caenorhabditis elegans. The reduction or loss of ced-3 or ced-4 function results in a transformation in the fates of cells that normally die; in ced-3 or ced-4 mutants, such cells instead survive and differentiate, adopting fates that in the wild type and associated with other cells. ced-3 and ced-4 mutants appear grossly normal in morphology and behavior, indicating that programmed cell…

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A Transcriptional Lineage of the Early C. elegans Embryo

Author: Tintori, Sophia C.; Osborne Nishimura, Erin; Golden, Patrick; Lieb, Jason D.; Goldstein, Bob Description: During embryonic development, cells must establish fates, morphologies, and behaviors in coordination with one another to form a functional body. A prevalent hypothesis for how this coordination is achieved is that each cell’s fate and behavior is determined by a defined mixture of RNAs. Only recently has it become possible to measure the full suite of transcripts in a single cell. Here we quantify genome-wide mRNA abundance in each cell of the Caenorhabditis elegans embryo…

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Cellular interactions in early C. elegans embryos

Author: Priess, J. R.; Thomson, J. N. Description: In normal development both the anterior and posterior blastomeres in a 2-cell C. elegans embryo produce some descendants that become muscles. We show that cellular interactions appear to be necessary in order for the anterior blastomere to produce these muscles. The anterior blastomere does not produce any muscle descendants after either the posterior blastomere or one of the daughters of the posterior blastomere is removed from the egg. Moreover, we demonstrate that a daughter of the anterior blastomere that normally does not…

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The glp-1 locus and cellular interactions in early C. elegans embryos

Author: Priess, J. R.; Schnabel, H.; Schnabel, R. Description: Interactions between the early blastomeres in a C. elegans embryo are required for the specification of certain cell fates. Blastomeres that produce neurons and skin cells when cultured in isolation are induced to also produce pharyngeal cells in intact embryos. We have identified maternal effect lethal mutations that, on the basis of phenotype and temperature-sensitive period, appear to disrupt this inductive interaction. These mutations are all alleles of glp-1, a gene also involved in the control of germ cell proliferation during…

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Identification of genes required for cytoplasmic localization in early C. elegans embryos

Author: Kemphues, K. J.; Priess, J. R.; Morton, D. G.; Cheng, N. S. Description: We have isolated and analyzed eight strict maternal effect mutations identifying four genes, par-1, par-2, par-3, and par-4, required for cytoplasmic localization in early embryos of the nematode C. elegans. Mutations in these genes lead to defects in cleavage patterns, timing of cleavages, and localization of germ line-specific P granules. Four mutations in par-1 and par-4 are fully expressed maternal effect lethal mutations; all embryos from mothers homozygous for these mutations arrest as amorphous masses of…

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HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans

Author: Treinin, M.; Shliar, J.; Jiang, H.; Powell-Coffman, J.A.; Bromberg, Z.; Horowitz, M. Description: Chronic exposure to environmental heat improves tolerance via heat acclimation (AC). Our previous data on mammals indicate that reprogramming the expression of genes coding for stress proteins and energy-metabolism enzymes plays a major role. Knowledge of pathways leading to AC is limited. For their identification, we established a Caenorhabditis elegans AC model and tested mutants in which signaling pathways pertinent to acclimatory responses are mutated. AC attained by maintaining adult C. elegans at 25 degrees C…

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