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2.
J Gerontol A Biol Sci Med Sci ; 74(8): 1198-1205, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-29099917

RESUMO

When cultured in axenic medium, Caenorhabditis elegans shows the largest life-span extension compared with other dietary restriction regimens. However, the underlying molecular mechanism still remains elusive. The gene cbp-1, encoding the worm ortholog of p300/CBP (CREB-binding protein), is one of the very few key genes known to be essential for life span doubling under axenic dietary restriction (ADR). By using tissue-specific RNAi, we found that cbp-1 expression in the germline is essential for fertility, whereas this gene functions specifically in the GABAergic neurons to support the full life span-doubling effect of ADR. Surprisingly, GABA itself is not required for ADR-induced longevity, suggesting a role of neuropeptide signaling. In addition, chemotaxis assays illustrate that neuronal inactivation of CBP-1 affects the animals' food sensing behavior. Together, our results show that the strong life-span extension in axenic medium is under strict control of GABAergic neurons and may be linked to food sensing.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Privação de Alimentos/fisiologia , Neurônios GABAérgicos/metabolismo , Expectativa de Vida , Proteínas de Ligação a RNA/metabolismo , Envelhecimento/fisiologia , Animais , Quimiotaxia , Meios de Cultura , Longevidade/fisiologia , Microscopia Confocal , Fenótipo
3.
J Gerontol A Biol Sci Med Sci ; 72(10): 1311-1318, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28329170

RESUMO

In Caenorhabditis elegans, a broad range of dietary restriction regimens extend life span to different degrees by separate or partially overlapping molecular pathways. One of these regimens, axenic dietary restriction, doubles the worm's life span but currently, almost nothing is known about the underlying molecular mechanism. Previous studies suggest that mitochondrial stress responses such as the mitochondrial unfolded protein response (UPRmt) or mitohormesis may play a vital role in axenic dietary restriction-induced longevity. Here, we provide solid evidence that axenic dietary restriction treatment specifically induces an UPRmt response in C elegans but this induction is not required for axenic dietary restriction-mediated longevity. We also show that reactive oxygen species-mediated mitohormesis is not involved in this phenotype. Hence, changes in mitochondrial physiology and induction of a mitochondrial stress response are not necessarily causal to large increases in life span.


Assuntos
Caenorhabditis elegans/metabolismo , Restrição Calórica , Expectativa de Vida , Mitocôndrias/metabolismo , Fatores Etários , Animais , Estresse Oxidativo , Fenótipo , Espécies Reativas de Oxigênio/metabolismo , Resposta a Proteínas não Dobradas
4.
Nat Commun ; 6: 8782, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26621324

RESUMO

Moderate levels of reactive oxygen species (ROS) are now recognized as redox signalling molecules. However, thus far, only mitochondria and NADPH oxidases have been identified as cellular sources of ROS in signalling. Here we identify a globin (GLB-12) that produces superoxide, a type of ROS, which serves as an essential signal for reproduction in C. elegans. We find that GLB-12 has an important role in the regulation of multiple aspects in germline development, including germ cell apoptosis. We further describe how GLB-12 displays specific molecular, biochemical and structural properties that allow this globin to act as a superoxide generator. In addition, both an intra- and extracellular superoxide dismutase act as key partners of GLB-12 to create a transmembrane redox signal. Our results show that a globin can function as a driving factor in redox signalling, and how this signal is regulated at the subcellular level by multiple control layers.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Globinas/metabolismo , Superóxidos/metabolismo , Animais , Caenorhabditis elegans/química , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Células Germinativas/metabolismo , Globinas/química , Globinas/genética , Modelos Moleculares , Reprodução , Transdução de Sinais
5.
Exp Gerontol ; 45(7-8): 603-10, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20096764

RESUMO

Reactive oxygen species have long been considered a major cause of aging. However, previous work showed that loss of superoxide dismutase (SOD) only weakly affects lifespan of Caenorhabditis elegans. Here, we examined the impact of sod gene deletion and overexpression on the mRNA levels of the remaining sod genes and other detoxification genes. We detected no compensatory upregulation of other sod genes in any of the sod deletion mutants in both wild-type and daf-2(m577) genetic backgrounds when L4 larvae were shifted from 17 to 24 degrees C, and harvested as young adults. Elimination of MnSOD increased transcription of SKN-1 regulated genes and reduced transcription of multiple DAF-16 targets. Loss of the major Cu/ZnSOD isoform SOD-1 caused enhanced expression of subsets of both SKN-1 and DAF-16 targets when the animals were grown continuously at 24 degrees C, and strong overexpression of sod-1 induced a compensatory decrease in all tested SKN-1 regulated gst genes. When combined, these results suggest that low cytosolic SOD may activate SKN-1 signaling, whereas high levels may be repressive. Overall, our results suggest that sod gene manipulation causes complex, combinatorial regulation of expression of individual targets of stress sensitive transcription factors.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/genética , Genes de Helmintos , Superóxido Dismutase/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Animais Geneticamente Modificados , Sítios de Ligação/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead , Fatores de Transcrição GATA/metabolismo , Deleção de Genes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Inativação Metabólica/genética , Inativação Metabólica/fisiologia , Longevidade/genética , Longevidade/fisiologia , Mutação , Estresse Oxidativo , Regiões Promotoras Genéticas , RNA de Helmintos/genética , RNA de Helmintos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Fatores de Transcrição/metabolismo
6.
Mol Phylogenet Evol ; 50(3): 642-53, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19141323

RESUMO

The siphonous green algae are an assemblage of seaweeds that consist of a single giant cell. They comprise two sister orders, the Bryopsidales and Dasycladales. We infer the phylogenetic relationships among the siphonous green algae based on a five-locus data matrix and analyze temporal aspects of their diversification using relaxed molecular clock methods calibrated with the fossil record. The multi-locus approach resolves much of the previous phylogenetic uncertainty, but the radiation of families belonging to the core Halimedineae remains unresolved. In the Bryopsidales, three main clades were inferred, two of which correspond to previously described suborders (Bryopsidineae and Halimedineae) and a third lineage that contains only the limestone-boring genus Ostreobium. Relaxed molecular clock models indicate a Neoproterozoic origin of the siphonous green algae and a Paleozoic diversification of the orders into their families. The inferred node ages are used to resolve conflicting hypotheses about species ages in the tropical marine alga Halimeda.


Assuntos
Clorófitas/genética , Evolução Molecular , Filogenia , Teorema de Bayes , Clorófitas/classificação , DNA de Algas/genética , Especiação Genética , Funções Verossimilhança , Modelos Genéticos , Alga Marinha/classificação , Alga Marinha/genética , Alinhamento de Sequência , Análise de Sequência de DNA
7.
J Phycol ; 45(3): 726-31, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27034048

RESUMO

The genus Pseudochlorodesmis (Bryopsidales) is composed of diminutive siphons of extreme morphological simplicity. The discovery of Pseudochlorodesmis-like juveniles in more complex Bryopsidales (e.g., the Halimeda microthallus stage) jeopardized the recognition of this genus. Confronted with this uncertainty, taxonomists transferred many simple siphons into a new genus, Siphonogramen. In this study, we used a multimarker approach to clarify the phylogenetic and taxonomic affinities of the Pseudochlorodesmis-Siphonogramen (PS) complex within the more morphologically complex bryopsidalean taxa. Our analyses reveal a new layer of diversity largely distinct from the lineages containing the structurally complex genera. The PS complex shows profound cryptic diversity exceeding the family level. We discuss a potential link between thallus complexity and the prevalence and profundity of cryptic diversity. For taxonomic simplicity and as a first step toward clarifying the taxonomy of these simple siphons, we propose to maintain Pseudochlorodesmis as a form genus and subsume Siphonogramen and Botryodesmis therein.

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