Endocrine targets for pharmacological intervention in aging in <i>Caenorhabditis elegans</i>

Gill, Matthew S.

doi:10.1111/j.1474-9726.2006.00186.x

Cited by 18 publications

(12 citation statements)

References 98 publications

(101 reference statements)

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“…Over the years the lipofuscin interpretation has been favored (see e.g., Gill, 2006; Masse et al, 2008; Fujii et al, 2009; Jain et al, 2009; Minniti et al, 2009), perhaps because of the good fit with the theory that aging is caused by accumulation of molecular damage. Unfortunately, this interpretation (i.e., that the blue fluorescent substance is lipofuscin) is not the correct one.…”

Section: The Gut Granule: An Enigmatic Nematode Organellementioning

confidence: 99%

The mysterious case of the C. elegans gut granule: death fluorescence, anthranilic acid and the kynurenine pathway

Coburn¹,

Gems²

2013

Front. Genet.

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Gut granules are lysosome-like organelles with acidic interiors that are found in large numbers within the intestine of the nematode Caenorhabditis elegans. They are particularly prominent when viewed under ultraviolet light, which causes them to emit intense blue fluorescence. Yet the function of these large and abundant organelles in this heavily-studied model organism remains unclear. One possibility is that they serve as storage organelles, for example of zinc. A new clue to gut granule function is the identification of the blue fluorescent material that they contain as a glycosylated form of anthranilic acid, which is derived from tryptophan by action of the kynurenine pathway. This compound can also serve a surprising role as a natural, endogenous marker of organismal death.

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Section: The Gut Granule: An Enigmatic Nematode Organellementioning

confidence: 99%

The mysterious case of the C. elegans gut granule: death fluorescence, anthranilic acid and the kynurenine pathway

Coburn¹,

Gems²

2013

Front. Genet.

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“…The nematode Caenorhabditis elegans is ideally suited for biogerontological research, not only because of its short life cycle (Gami and Wolkow, 2006; Gill, 2006; Kaletta and Hengartner, 2006) but also due to the considerable conservation of basic cellular and molecular principles (The C. elegans Sequencing Consortium, 1998). …”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Global Transcriptomics Suggests that Conserved Genetic Pathways are Responsible for Quercetin and Tannic Acid Mediated Longevity in C. elegans

Pietsch¹,

Saul²,

Swain³

et al. 2012

Front. Gene.

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Recent research has highlighted that the polyphenols Quercetin and Tannic acid are capable of extending the lifespan of Caenorhabditis elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to three concentrations of Quercetin or Tannic acid, respectively. By means of an intricate meta-analysis it was possible to compare the transcriptomes of polyphenol exposure to recently published datasets derived from (i) longevity mutants or (ii) infection. This detailed comparative in silico analysis facilitated the identification of compound specific and overlapping transcriptional profiles and allowed the prediction of putative mechanistic models of Quercetin and Tannic acid mediated longevity. Lifespan extension due to Quercetin was predominantly driven by the metabolome, TGF-beta signaling, Insulin-like signaling, and the p38 MAPK pathway and Tannic acid’s impact involved, in part, the amino acid metabolism and was modulated by the TGF-beta and the p38 MAPK pathways. DAF-12, which integrates TGF-beta and Insulin-like downstream signaling, and genetic players of the p38 MAPK pathway therefore seem to be crucial regulators for both polyphenols. Taken together, this study underlines how meta-analyses can provide an insight of molecular events that go beyond the traditional categorization into gene ontology-terms and Kyoto encyclopedia of genes and genomes-pathways. It also supports the call to expand the generation of comparative and integrative databases, an effort that is currently still in its infancy.

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“…In the model organism nematode, Caenorhabditis elegans ( C. elegans ), there are many reports that dietary supplements, such as antioxidants and radical scavengers, extended the lifespan. C. elegans is an excellent experimental system to assess the pharmacological influence on intracellular aging pathways conserved between invertebrates and vertebrates [3, 4]. For example, it is conceivable that antioxidants, such as vitamin E, simply act to reduce the intracellular ROS in C. elegans [5].…”

Section: Introductionmentioning

confidence: 99%

Supplemental Cellular Protection by a Carotenoid Extends Lifespan via Ins/IGF-1 Signaling inCaenorhabditis elegans

Yazaki

Yoshikoshi

Oshiro

et al. 2011

Oxidative Medicine and Cellular Longevity

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Astaxanthin (AX), which is produced by some marine animals, is a type of carotenoid that has antioxidative properties. In this study, we initially examined the effects of AX on the aging of a model organism C. elegans that has the conserved intracellular pathways related to mammalian longevity. The continuous treatments with AX (0.1 to 1 mM) from both the prereproductive and young adult stages extended the mean lifespans by about 16–30% in the wild-type and long-lived mutant age-1 of C. elegans. In contrast, the AX-dependent lifespan extension was not observed even in a daf-16 null mutant. Especially, the expression of genes encoding superoxide dismutases and catalases increased in two weeks after hatching, and the DAF-16 protein was translocated to the nucleus in the AX-exposed wild type. These results suggest that AX protects the cell organelle mitochondria and nucleus of the nematode, resulting in a lifespan extension via an Ins/IGF-1 signaling pathway during normal aging, at least in part.

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Endocrine targets for pharmacological intervention in aging in Caenorhabditis elegans

Cited by 18 publications

References 98 publications

The mysterious case of the C. elegans gut granule: death fluorescence, anthranilic acid and the kynurenine pathway

The mysterious case of the C. elegans gut granule: death fluorescence, anthranilic acid and the kynurenine pathway

Meta-Analysis of Global Transcriptomics Suggests that Conserved Genetic Pathways are Responsible for Quercetin and Tannic Acid Mediated Longevity in C. elegans

Supplemental Cellular Protection by a Carotenoid Extends Lifespan via Ins/IGF-1 Signaling inCaenorhabditis elegans

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