Transcriptional Profile of Aging in C. elegans

Lund, John E.; Tedesco, Patricia M.; Duke, Kyle; Wang, John; Kim, Stuart K.; Johnson, Thomas E.

doi:10.1016/s0960-9822(02)01146-6

Cited by 254 publications

(210 citation statements)

References 46 publications

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“…Most transcriptional changes were specific to worms or to flies. For example, in these experiments and other work 13 , aging in C. elegans repressed genes encoding collagens and induced genes encoding histones, transposases and DNA and RNA helicases; these changes did not characterize D. melanogaster aging. Aging in D. melanogaster induced genes encoding cytochrome p450s, glycosylases and peptidoglycan receptors, but aging in C. elegans did not alter the expression of the orthologous genes.…”

Section: Biological Features Of Conserved Regulationmentioning

confidence: 63%

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

et al. 2004

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We developed a method for systematically comparing gene expression patterns across organisms using genome-wide comparative analysis of DNA microarray experiments. We identified analogous gene expression programs comprising shared patterns of regulation across orthologous genes. Biological features of these patterns could be identified as highly conserved subpatterns that correspond to Gene Ontology categories. Here, we demonstrate these methods by analyzing a specific biological process, aging, and show that similar analysis can be applied to a range of biological processes. We found that two highly diverged animals, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, implement a shared adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport. Most of these changes were implemented early in adulthood. Using this approach to search databases of gene expression data, we found conserved transcriptional signatures in larval development, embryogenesis, gametogenesis and mRNA degradation.Gene expression profiling measures the expression levels of thousands of genes at once 1,2 . Most expression profiling studies have focused on the specific genes that respond to specific conditions, but another important direction in functional genomics is to derive insight from global patterns of gene expression. Genome-scale expression patterns have been used as physiological 'fingerprints' for classifying tumors 3,4 and assigning uncharacterized mutations and drugs to known pathways 5 . Because they use information from many genes at once, patterns have great discriminating power, even when the transcriptional effects on individual genes are small 5,6 .The patterns of changes in gene expression observed in microarray experiments can be extensive and complex. To try to analyze these patterns, we exploited the principle that important biological processes are often conserved between organisms. We present an approach to comparative functional genomics based on shared patterns of regulation across orthologous genes. We also present a method for identifying conserved biological components of those patterns that correspond to Gene Ontology categories. These methods can be used to search databases of microarray experiments to discover connections among biological processes in different organisms. RESULTS Comparing genomic expression patterns across speciesWe used phylogenetic analysis to systematically identify orthologous groups of genes for all pairwise comparisons between C. elegans, D. melanogaster, Saccharomyces cerevisiae and Homo sapiens (Supplementary Tables 1-5 online). For C. elegans and D. melanogaster, we identified 3,851 most-conserved orthologous gene pairs (Fig. 1a).We used DNA microarrays in each organism to compare gene expression under different conditions (Fig. 1b). We then used gene phylogenetic relationships to match systematically the measurements of differential expression between orthologous genes from the tw...

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Section: Biological Features Of Conserved Regulationmentioning

confidence: 63%

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

et al. 2004

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“…Previously, whole-genome transcriptional profiles of worm populations of varying ages were generated using DNA microarrays [8,9] A concept of interest is to use biomarkers of aging to predict the lifespan of individuals within a population with an identical age and sharing the same environment. Levels of lipofuscin, a pigment thought to correlate with physiological age, were found to predict the remaining lifespan of worms [14].…”

Section: Transcriptional Profiles Of Aging In C Elegansmentioning

confidence: 99%

Systems biology of aging in four species

Zahn

Kim

2007

Current Opinion in Biotechnology

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Using DNA microarrays to generate transcriptional profiles of the aging process is a powerful tool for identifying biomarkers of aging. In C. elegans, a number of whole-genome profiling studies identified genes that change expression levels with age. High-throughput RNAi screens in worms determined a number of genes that modulate lifespan when silenced. Transcriptional profiling of the fly head identified a molecular pathway, the 'response to light' gene set, that increases expression with age and could be directly related to the tendency for a reduction in light levels to extend fly lifespan. In mouse, comparing the gene expression profiles of several drugs to the gene expression profile of caloric restriction identified metformin as a drug whose action could potentially mimic caloric restriction in vivo. Finally, genes in the mitochondrial electron transport chain group decrease expression with age in the human, mouse, fly, and worm.

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“…When we analyzed the later release WS160 (http://ws160.wormbase.org), four of these nine tags were found to overlap with newly established curated coding genes (Y82E9BR.22, T07A5.5, C08A9.10 and W10C8.6). Lund et al (2002) derived a list of 164 aging-associated genes using microarray analysis at different times in adulthood, from young adults to adults at and beyond the median life expectancy. Less than half (69 genes total) of the reported genes were detected in any of our eight libraries (8429 genes), and only four of the 164 genes were found on our list of 120 putative longevity-related genes (Suppl.…”

Section: Discovery Of New Aging-related Genesmentioning

confidence: 99%

“…Whereas McElwee et al (2004) used cDNA microarrays for a similar comparison, we used Serial Analysis of Gene Expression, or SAGE (Velculescu et al, 1995) to identify potential novel regulators of life span, and to characterize the expression profiles of different gene families that were previously shown to be associated with aging (Lund et al, 2002;Murphy et al, 2003). SAGE data for daf-2 and wild-type adults were compared in a previous study (Halaschek-Wiener et al, 2005), which showed general inhibition of metabolism in the middleaged daf-2 adults.…”

Section: Introductionmentioning

confidence: 99%

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

Ruzanov

Riddle

Marra

et al. 2007

Experimental Gerontology

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SummaryWe used Serial Analysis of Gene Expression (SAGE) to compare the global transcription profiles of long-lived mutant daf-2 adults and dauer larvae, aiming to identify aging-related genes based on similarity of expression patterns. Genes that are expressed similarly in both long-lived types potentially define a common life-extending program. Comparison of eight SAGE libraries yielded a set of 120 genes, the expression of which was significantly different in long-lived worms versus normal adults. The gene annotations indicate a strong link between oxidative stress and life span, further supporting the hypothesis that metabolic activity is a major determinant in longevity. The SAGE data show changes in mRNA levels for electron transport chain components, elevated expression of glyoxylate shunt enzymes and significantly reduced expression for components of the TCA cycle in longer-lived nematodes. We propose a model for enhanced longevity through a cytochrome c oxidase-mediated reduction in reactive oxygen species commonly held to be a major contributor to aging.

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Transcriptional Profile of Aging in C. elegans

Abstract: We have performed a whole-genome analysis of changes in gene expression during aging in C. elegans that provides a molecular description of C. elegans senescence.

Cited by 254 publications

References 46 publications

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

Comparing genomic expression patterns across species identifies shared transcriptional profile in aging

Systems biology of aging in four species

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

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