The NetAge database: a compendium of networks for longevity, age-related diseases and associated processes

Tăcutu, Robi; Budovsky, Arie; Fraifeld, Vadim E.

doi:10.1007/s10522-010-9265-8

Cited by 74 publications

(63 citation statements)

References 52 publications

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“…The construction of longevity networks has been described previously (Tacutu et al ., 2010). Briefly, the networks include LAGs as a core set and their first‐order interaction partners.…”

Section: Methodsmentioning

confidence: 99%

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

et al. 2015

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SummaryCaloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene expression profiles with CR. Eleven statistically significant compounds were predicted as CR mimetics using this bioinformatics approach. We then tested rapamycin, allantoin, trichostatin A, LY‐294002 and geldanamycin in Caenorhabditis elegans. An increase in lifespan and healthspan was observed for all drugs except geldanamycin when fed to wild‐type worms, but no lifespan effects were observed in eat‐2 mutant worms, a genetic model of CR, suggesting that life‐extending effects may be acting via CR‐related mechanisms. We also treated daf‐16 worms with rapamycin, allantoin or trichostatin A, and a lifespan extension was observed, suggesting that these drugs act via DAF‐16‐independent mechanisms, as would be expected from CR mimetics. Supporting this idea, an analysis of predictive targets of the drugs extending lifespan indicates various genes within CR and longevity networks. We also assessed the transcriptional profile of worms treated with either rapamycin or allantoin and found that both drugs use several specific pathways that do not overlap, indicating different modes of action for each compound. The current work validates the capabilities of this bioinformatic drug repositioning method in the context of longevity and reveals new putative CR mimetics that warrant further studies.

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“…The construction of longevity networks has been described previously (Tacutu et al ., 2010). Briefly, the networks include LAGs as a core set and their first‐order interaction partners.…”

Section: Methodsmentioning

confidence: 99%

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

et al. 2015

Self Cite

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“…18 'Cluster' of genes, known to be involved in inflammation, were identified using Rat Genome database and Netage database. 64,65 Functional gene-gene network interaction was inferred using STRING tool and literature search. 66,67 STRING uses diverse method to predict relationship among genes which include neighborhood, gene fusion, co-occurrence co-expression, experiments, databases and text-mining.…”

Section: Gene Expression By Qpcrmentioning

confidence: 99%

Islet adaptation to obesity and insulin resistance in WNIN/GR-Ob rats

Singh¹,

Ganneru²,

Malakapalli³

et al. 2014

Islets

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WNIN/GR-Ob mutant rat is a novel animal model to study metabolic syndrome (obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance and cardiovascular diseases). We have investigated the islet characteristics of obese mutants at different age groups (1, 6 and 12 months) to assess the islet changes in response to early and chronic metabolic stress. Our data demonstrates altered islet cell morphology and function (hypertrophy, fibrotic lesions, vacuolation, decreased stimulation index, increased TNFa, ROS and TBARS levels) in mutants as compared to controls. Furthermore, network analysis (gene-gene interaction) studied in pancreas demonstrated increased inflammation as a key factor underlying obesity/metabolic syndrome in mutants. These observations pave way to explore this model to understand islet adaptation in response to metabolic syndrome.

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“…There are only nine databases with information on molecular interactions. [53][54][55][56][57][58][59][60][61] Most of these annotations are related to interaction between ncRNA and their target transcripts in an RNA:RNA relationship; little information is available covering RNA:protein or RNA:DNA relationships. Discovering new functional mechanisms of these molecules is a big challenge, which is crucial for understanding the functionality of these ubiquitous transcripts in eukaryotic genomes.…”

Section: Do Not Distributementioning

confidence: 99%

Non-coding transcription characterization and annotation

et al. 2012

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Large-scale transcriptome projects have shown that the number of RNA transcripts not coding for proteins (noncoding RNAs) is much larger than previously recognized. High-throughput technologies, coupled with bioinformatics approaches, have produced increasing amounts of data, highlighting the role of non-coding RNAs (ncRNAs) in biological processes. Data generated by these studies include diverse non-coding RNA classes from organisms of different kingdoms, which were obtained using different experimental and computational assays. This has led to a rapid increase of specialized RNA databases. The fast growth in the number of available databases makes integration of stored information a difficult task. We present here NRDR, a Non-coding RNA Databases Resource for information retrieval on ncRNA databases (www.ncrnadatabases.org). We performed a survey of 102 public databases on ncRNAs and we have introduced four categorizations to classify these databases and to help researchers quickly search and find the information they need: RNA family, information source, information content and available search mechanisms. NRDR is a useful databases searching tool that will facilitate research on ncRNAs.

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The NetAge database: a compendium of networks for longevity, age-related diseases and associated processes

Cited by 74 publications

References 52 publications

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

Islet adaptation to obesity and insulin resistance in WNIN/GR-Ob rats

Non-coding transcription characterization and annotation

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