Genomic approaches for the understanding of aging in model organisms

Park, Sang-Kyu

doi:10.5483/bmbrep.2011.44.5.291

Cited by 10 publications

(11 citation statements)

References 47 publications

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“…The DEFOG analysis indicates that the aging genes are broken up into the following functional units: hormone-related signalling (Fig 2c:1), apoptosis (Fig 2c:2), regulation of phosphorylation (Fig 2c:3), DNA damage response (Fig 2c:4), transcription factor regulation (Fig 2c:5), nucleotide-excision repair (Fig 2c:6), transcription factor DNA-binding activity (Fig 2c:7), cholesterol regulation (Fig 2c:8), regulation of signal transduction via MAPKKK cascades (Fig 2c:9), and regulation of signal transduction via the JAK-STAT cascade (Fig 2c:10). These major functional categories correlate well with what is known about aging systems in the body and the pathways that are affected during aging 52-54 . Despite the disparate nature of the gene functions within the GenAge gene list, DEFOG was able to group the genes into functional categories that are both useful and informative on many levels.…”

Section: Resultssupporting

confidence: 71%

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DEFOG: discrete enrichment of functionally organized genes

Wittkop¹,

Berman²,

Fleisch³

et al. 2012

Integr. Biol.

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High-throughput biological experiments commonly result in a list of genes or proteins of interest. In order to understand the observed changes of the genes and to generate new hypotheses, one needs to understand the functions and roles of the genes and how those functions relate to the experimental conditions. Typically, statistical tests are performed in order to detect enriched Gene Ontology categories or Pathways, i.e. the categories are observed in the genes of interest more often than is expected by chance. Depending on the number of genes and the complexity and quantity of functions in which they are involved, such an analysis can easily result in hundreds of enriched terms. To this end we developed DEFOG, a web-based application that facilitates the functional analysis of gene sets by hierarchically organizing the genes into functionally related modules. Our computational pipeline utilizes three powerful tools to achieve this goal: (1) GeneMANIA creates a functional consensus network of the genes of interest based on gene-list-specific data fusion of hundreds of genomic networks from publicly available sources; (2) Transitivity Clustering organizes those genes into a clear hierarchy of functionally related groups, and (3) Ontologizer performs a Gene Ontology enrichment analysis on the resulting gene clusters. DEFOG integrates this computational pipeline within an easy-to-use web interface, thus allowing for a novel visual analysis of gene sets that aids in the discovery of potentially important biological mechanisms and facilitates the creation of new hypotheses. DEFOG is available at http://www.mooneygroup.org/defog.

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Section: Resultssupporting

confidence: 71%

“…In this experiment, we utilized a set of manually curated aging-related genes from the GenAge database. Aging is among the most complex and widely functionally distributed biological processes currently being researched 52 . As such, the GenAge gene list is equally disparate in gene function.…”

Section: Discussionmentioning

confidence: 99%

DEFOG: discrete enrichment of functionally organized genes

Wittkop¹,

Berman²,

Fleisch³

et al. 2012

Integr. Biol.

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“…Current approaches to determining the role of a gene in the aging process include animal models in which either gain or loss of function mutations result in changes in lifespan and comparative human studies of long-lived cohorts [1-4]. With respect to human studies, age-related genes have been identified by a variety of approaches including comparison of differential gene expression in older individuals (particularly centenarians) with younger individuals, longitudinal studies of octogenarians and nonagenarians to identify genes that are differentially expressed in those that reach 100 years of age, and determination of genes in which naturally occurring polymorphisms or mutations result in a change in the aging process [5].…”

Section: Introductionmentioning

confidence: 99%

Conservation of pro-longevity genes among mammals

Lindborg

Propert

Pignolo

2015

Mechanisms of Ageing and Development

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Genes which confer a relative longevity advantage may be regulated at the level of transcription or translation. Alternatively, pro-longevity genes may mediate their effects at the level of protein structure-functional relationships that are beneficially optimized in long-lived species. Longevity associated genes (LAGs) may be operationally defined as genes that confer beneficial effects and are relatively more conserved among long-lived species. Global and local protein sequence alignments of over 10,000 genes across at least 30 mammalian species were examined to identify LAGs. Known LAGs, including growth hormone receptor (GHR), and breast cancer 1, early onset (BRCA1), have strong associations with maximum lifespan by our analysis. Several common categories of protein function were observed among genes ranked with the strongest associations with MLS identified by all regression models. These genes included those that function in the immune system, cell cycle regulation, and DNA damage response. We provide a ranking of genes with the strongest associations with species maximum lifespan (MLS) by several phylogenetic generalized least squares regression models, including adjustment for confounding variables such as body weight and gestation length.

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“…From a biological point of view, aging is an universal, progressive, and irreversible decline of function over time, resulting in reduction of cell function and eventually cell death [1]. Aging-related biochemical and cell-biological changes of cardiomyocytes lead to pathophysiological conditions, especially reduced heart function and heart diseases [2].…”

Section: Introductionmentioning

confidence: 99%

Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State

Dong

et al. 2013

PLoS ONE

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BackgroundCell senescence is central to a large body of age related pathology, and accordingly, cardiomyocytes senescence is involved in many age related cardiovascular diseases. In consideration of that, delaying cardiomyocytes senescence is of great importance to control clinical cardiovascular diseases. Previous study indicated that bradykinin (BK) protected endothelial cells from senescence induced by oxidative stress. However, the effects of bradykinin on cardiomyocytes senescence remain to be elucidated. In this study, we investigated the effect of bradykinin on H2O2-induced H9C2 cells senescence.Methods and ResultsBradykinin pretreatment decreased the senescence induced by H2O2 in cultured H9C2 cells in a dose dependent manner. Interestingly, 1 nmol/L of BK almost completely inhibited the increase in senescent cell number and p21 expression induced by H2O2. Since H2O2 induces senescence through superoxide-induced DNA damage, we also observed the DNA damage by comet assay, and BK markedly reduced DNA damage induced by H2O2, and moreover, BK treatment significantly prevented reactive oxygen species (ROS) production in H9C2 cells treated with H2O2. Importantly, when co-incubated with bradykinin B2 receptor antagonist HOE-140 or eNOS inhibitor N-methyl-L-arginine acetate salt (L-NAME), the protective effects of bradykinin on H9C2 senescence were totally blocked. Furthermore, BK administration significantly prevented the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity characterized by increased ROS generation and gp91 expression and increased translocation of p47 and p67 to the membrane and the decrease in superoxide dismutase (SOD) activity and expression induced by H2O2 in H9C2 cells, which was dependent on BK B2 receptor mediated nitric oxide (NO) release.ConclusionsBradykinin, acting through BK B2 receptor induced NO release, upregulated antioxidant Cu/Zn-SOD and Mn-SOD activity and expression while downregulating NADPH oxidase activity and subsequently inhibited ROS production, and finally protected against cardiomyocytes senescence induced by oxidative stress.

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Genomic approaches for the understanding of aging in model organisms

Cited by 10 publications

References 47 publications

DEFOG: discrete enrichment of functionally organized genes

DEFOG: discrete enrichment of functionally organized genes

Conservation of pro-longevity genes among mammals

Bradykinin Inhibits Oxidative Stress-Induced Cardiomyocytes Senescence via Regulating Redox State

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