Comparing genomic expression patterns across species identifies shared transcriptional profile in aging
Abstract
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.
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GBA approaches are widely used to identify new potential disease genes if a substantial proportion of the genes within a module are associated with a particular disease.
“GBA approaches are also widely used to identify new potential disease genes if a substantial proportion of the genes within a module are associated with a particular disease [26, 121–126] (Figure 1).”
From Gene co-expression analysis for functional classification and gene–disease predictions (2017) · cites this paper as [125]
Deregulation of mitochondrial function is a common feature across multiple aspects of aging.
“Deregulation of mitochondrial function is a common feature in multiple aspects of aging.”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [6]
The cited findings suggest mitochondrial dysfunction has a causal role in aging and mitochondrial adaptation is central to CR's retardation of aging.
“Taken together these findings suggest of a causal role of mitochondrial dysfunction in the aging process and a central role for mitochondrial adaptation in the mechanism of aging retardation by CR”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [6]
Genes involved in mitochondrial energy metabolism are among the key pathways universally regulated with aging.
“Foremost among these and pertinent to this review are genes involved in mitochondrial energy metabolism.”
From PGC-1α in aging and anti-aging interventions (2009) · cites this paper as [6]
Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Gene Expression Omnibus: NCBI gene expression and hybridization array data repository
Edgar, R. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.207 · Cited by 13,288 · see citing works
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413 · see citing works
Exploring the metabolic and genetic control of gene expression on a genomic scale.
Derisi, J., Iyer, V., & Brown, P. (1997) · Science · doi:10.1126/science.278.5338.680 · Cited by 4,832 · see citing works
Quantitative analysis of complex protein mixtures using isotope-coded affinity tags
Gygi, S. P., Rist, B., Gerber, S. A., Turecek, F., Gelb, M. H., & Aebersold, R. (1999) · Nature Biotechnology · doi:10.1038/13690 · Cited by 4,683 · cited 1× · see citing works
“Our computational approach is also readily generalized to data on protein expression and modificatio”
MethodA C. elegans mutant that lives twice as long as wild type
Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993) · Nature · doi:10.1038/366461a0 · Cited by 3,387 · see citing works
Self-citationFunctional Discovery via a Compendium of Expression Profiles
Hughes, T. R., Marton, M. J., Jones, A. R., Roberts, C. J., Stoughton, R. B., Armour, C. D., Bennett, H. A., Coffey, E. M., Dai, H. A., He, Y. D., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00015-5 · Cited by 2,534 · see citing works
A molecular signature of metastasis in primary solid tumors
Ramaswamy, S., Ross, K. N., Lander, E. S., & Golub, T. R. (2002) · Nature Genetics · doi:10.1038/ng1060 · Cited by 2,448 · see citing works
Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
Murphy, C. T., McCarroll, S. A., Bargmann, C. I., Fraser, A., Kamath, R. S., Ahringer, J., Li, H., & Kenyon, C. (2003) · Nature · doi:10.1038/nature01789 · Cited by 2,280 · see citing works
Self-citationKimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997) · Science · doi:10.1126/science.277.5328.942 · Cited by 2,250 · see citing works
A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules
Stuart, J. M., Segal, E., Koller, D., & Kim, S. K. (2003) · Science · doi:10.1126/science.1087447 · Cited by 2,235 · see citing works
High density synthetic oligonucleotide arrays
Lipshutz, R. J., Fodor, S. P. A., Gingeras, T., & Lockhart, D. J. (1999) · Nature Genetics · doi:10.1038/4447 · Cited by 2,204 · see citing works
The Transcriptional Program of Sporulation in Budding Yeast
Chu, S., DeRisi, J. L., Eisen, M. B., Mulholland, J., Botstein, D., Brown, P. O., & Herskowitz, I. (1998) · Science · doi:10.1126/science.282.5389.699 · Cited by 1,860 · see citing works
Comparative Genomics of the Eukaryotes
Rubin, G. M., Yandell, M. D., Wortman, J. R., Gabor, G. L., Miklos, Nelson, C. R., Hariharan, I. K., Fortini, M. E., Li, P. W., Apweiler, R., et al. (2000) · Science · doi:10.1126/science.287.5461.2204 · Cited by 1,698 · see citing works
Segal, E., Shapira, M., Regev, A., Pe’er, D., Botstein, D., Koller, D., & Friedman, N. (2003) · Nature Genetics · doi:10.1038/ng1165 · Cited by 1,686 · see citing works
Whitfield, M. L., Sherlock, G., Saldanha, A. J., Murray, J. I., Ball, C. A., Alexander, K. E., Matese, J. C., Perou, C. M., Hurt, M. M., Brown, P. O., et al. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.02-02-0030 · Cited by 1,527 · see citing works
Gene expression profile of aging and its retardation by caloric restriction
Lee, C.-K., Klopp, R. G., Weindruch, R., & Prolla, T. A. (1999) · Science · doi:10.1126/science.285.5432.1390 · Cited by 1,473 · see citing works
Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue
Blüher, M., Kahn, B. B., & Kahn, C. R. (2003) · Science · doi:10.1126/science.1078223 · Cited by 1,348 · see citing works
Rates of Behavior and Aging Specified by Mitochondrial Function During Development
Dillin, A., Hsu, A.-L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A. G., Kamath, R. S., Ahringer, J., & Kenyon, C. (2002) · Science · doi:10.1126/science.1077780 · Cited by 1,121 · see citing works
Self-citationArrayExpress--a public repository for microarray gene expression data at the EBI
Parkinson, H. (2004) · Nucleic Acids Research · doi:10.1093/nar/gki056 · Cited by 1,075 · see citing works
Signals from the reproductive system regulate the lifespan of C. elegans
Hsin, H., & Kenyon, C. J. (1999) · Nature · doi:10.1038/20694 · Cited by 1,015 · see citing works
Self-citationGene Expression During the Life Cycle of Drosophila melanogaster
Arbeitman, M. N., Furlong, E. E. M., Imam, F. B., Johnson, E. A., Null, B. H., Baker, B. S., Krasnow, M. A., Scott, M. P., Davis, R. W., & White, K. P. (2002) · Science · doi:10.1126/science.1072152 · Cited by 926 · see citing works
Lithgow, G. J., White, T. M., Melov, S., & Johnson, T. E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7540 · Cited by 862 · see citing works
ArrayExpress--a public repository for microarray gene expression data at the EBI
Brāzma, A. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg091 · Cited by 776 · see citing works
Individuality and variation in gene expression patterns in human blood
Whitney, A. R., Diehn, M., Popper, S. J., Alizadeh, A. A., Boldrick, J. C., Relman, D. A., & Brown, P. O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252784499 · Cited by 775 · see citing works
Precision and functional specificity in mRNA decay
Wang, Y., Liu, C. L., Storey, J. D., Tibshirani, R. J., Herschlag, D., & Brown, P. O. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092538799 · Cited by 708 · see citing works
Lewis, J. A., & Fleming, J. T. (1995) · PubMed · Cited by 606 · see citing works
A Global Profile of Germline Gene Expression in C. elegans
Reinke, V., Smith, H. E., Nance, J., Wang, J., Doren, C. V., Begley, R., Jones, S. J. M., Davis, E. B., Scherer, S., Ward, S. F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00059-9 · Cited by 578 · see citing works
Genome-Wide Transcript Profiles in Aging and Calorically Restricted Drosophila melanogaster
Pletcher, S. D., Macdonald, S. J., Marguerie, R., Certa, U., Stearns, S. C., Goldstein, D. B., & Partridge, L. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00808-4 · Cited by 568 · see citing works
Self-citationThe Stanford Microarray Database
Sherlock, G. J. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.152 · Cited by 534 · see citing works
Wang, D. Y.-C., Kumar, S., & Hedges, S. B. (1999) · Proceedings of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rspb.1999.0617 · Cited by 493 · see citing works
Timing Requirements for Insulin/IGF-1 Signaling in C. elegans
Dillin, A., Crawford, D. K., & Kenyon, C. J. (2002) · Science · doi:10.1126/science.1074240 · Cited by 467 · see citing works
Self-citationStereotyped and specific gene expression programs in human innate immune responses to bacteria
Boldrick, J. C., Alizadeh, A. A., Diehn, M., Dudoit, S., Liu, C. L., Belcher, C. E., Botstein, D., Staudt, L. M., Brown, P. O., & Relman, D. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231625398 · Cited by 390 · see citing works
Kayo, T., Allison, D. B., Weindruch, R., & Prolla, T. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081061898 · Cited by 384 · see citing works
Regulation of Organogenesis by the Caenorhabditis elegans FoxA Protein PHA-4
Gaudet, J., & Mango, S. E. (2002) · Science · doi:10.1126/science.1065175 · Cited by 363 · see citing works
Genome-wide study of aging and oxidative stress response in Drosophila melanogaster
Zou, S., Meadows, S. A., Sharp, L., Jan, L. Y., & Jan, Y. N. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.260496697 · Cited by 313 · see citing works
Self-citationTranscriptional Profile of Aging in C. elegans
Lund, J., Tedesco, P. M., Duke, K., Wang, J., Kim, S. K., & Johnson, T. E. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01146-6 · Cited by 304 · see citing works
Alter, O., Brown, P. O., & Botstein, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0530258100 · Cited by 304 · see citing works
Genomic Analysis of Gene Expression in C. elegans
Hill, A. A. V., Hunter, C. P., Tsung, B. T., Tucker‐Kellogg, G., & Brown, E. L. (2000) · Science · doi:10.1126/science.290.5492.809 · Cited by 299 · see citing works
Jiang, M., Ryu, J., Kiraly, M., Duke, K., Reinke, V., & Kim, S. K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.1.218 · Cited by 285 · see citing works
Molecular portraits and the family tree of cancer
Chung, C. H., Bernard, P. S., & Perou, C. M. (2002) · Nature Genetics · doi:10.1038/ng1038 · Cited by 264 · see citing works
Genome-wide analysis of mRNA decay in resting and activated primary human T lymphocytes
Raghavan, A. (2002) · Nucleic Acids Research · doi:10.1093/nar/gkf682 · Cited by 233 · see citing works
Guillemin, K. J., Salama, N. R., Tompkins, L. S., & Falkow, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182558799 · Cited by 222 · see citing works
Predicting gene function by conserved co-expression
van Noort, V., Snel, ., & Huynen, M. A. (2003) · Trends in Genetics · doi:10.1016/s0168-9525(03)00056-8 · Cited by 192 · see citing works
Microarray databases: standards and ontologies
Stoeckert, C. J., Causton, H. C., & Ball, C. A. (2002) · Nature Genetics · doi:10.1038/ng1028 · Cited by 159 · see citing works
Detweiler, C. S., Cunanan, D. B., & Falkow, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091110098 · Cited by 119 · see citing works
Conservation of gene co-regulation in prokaryotes and eukaryotes
Teichmann, S. A., & Babu, M. M. (2002) · Trends in biotechnology · doi:10.1016/s0167-7799(02)02032-2 · Cited by 115 · see citing works
Gene Expression Pattern in Caco-2 Cells following Rotavirus Infection
Cuadras, M. A., Feigelstock, D., An, S., & Greenberg, H. B. (2002) · Journal of Virology · doi:10.1128/jvi.76.9.4467-4482.2002 · Cited by 86 · see citing works
A systematic approach to reconstructing transcription networks in Saccharomyces cerevisiae
Wang, W., Cherry, J. M., Botstein, D., & Li, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252638199 · Cited by 86 · see citing works
Self-citationInfluence of age on caloric expenditure during exercise.
Sm, S., Buckenmeyer, P. J., Sn, D., Rh, M., Verhulst, S. J., & Rg, K. (1992) · PubMed · Cited by 8 · see citing works
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Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · see citing works
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874 · see citing works
Cell intrinsic alterations underlie hematopoietic stem cell aging
Rossi, D. J., Bryder, D., Zahn, J. M., Ahlenius, H., Sonu, R., Wagers, A. J., & Weissman, I. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503280102 · Cited by 1,152 · see citing works
Role of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103 · see citing works
Gene co-expression analysis for functional classification and gene–disease predictions
van Dam, S., Võsa, U., van der Graaf, A., Franke, L., & de Magalhães, J. P. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbw139 · Cited by 1,086 · see citing works
Trends in oxidative aging theories
Muller, F. L., Lustgarten, M. S., Jang, Y., Richardson, A., & Van Remmen, H. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.03.034 · Cited by 1,053 · see citing works
Meta-analysis of age-related gene expression profiles identifies common signatures of aging
de Magalhães, J. P., Curado, J., & Church, G. M. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp073 · Cited by 737 · see citing works
The transcriptional landscape of age in human peripheral blood
Peters, M. J., Joehanes, R., Pilling, L. C., Schurmann, C., Conneely, K. N., Powell, J., Reinmaa, E., Sutphin, G. L., Zhernakova, A., Schramm, K., et al. (2015) · Nature Communications · doi:10.1038/ncomms9570 · Cited by 725 · see citing works
Yankner, B. A., Lu, T., & Loerch, P. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.2.010506.092044 · Cited by 677 · see citing works
With TOR, Less Is More: A Key Role for the Conserved Nutrient-Sensing TOR Pathway in Aging
Kapahi, P., Chen, D., Rogers, A. N., Katewa, S. D., Li, P. W.-L., Thomas, E., & Kockel, L. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.05.001 · Cited by 663 · see citing works
Collapse of proteostasis represents an early molecular event in <i>Caenorhabditis elegans</i> aging
Ben-Zvi, A., Miller, E. A., & Morimoto, R. I. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902882106 · Cited by 649 · see citing works
Genome sequence of the model mushroom Schizophyllum commune
Ohm, R. A., de Jong, J. F., Lugones, L. G., Aerts, A. L., Kothe, E., Stajich, J., de Vries, R. P., Record, É., Levasseur, A., Baker, S., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1643 · Cited by 554 · see citing works
4E-BP Extends Lifespan upon Dietary Restriction by Enhancing Mitochondrial Activity in Drosophila
Zid, B. M., Rogers, A. N., Katewa, S. D., Vargas, M. A., Kolipinski, M., Lu, T. A., Benzer, S., & Kapahi, P. (2009) · Cell · doi:10.1016/j.cell.2009.07.034 · Cited by 541 · see citing works
Age-associated alteration of gene expression patterns in mouse oocytes
Hamatani, T., Falco, G., Carter, M. G., Akutsu, H., Stagg, C. A., Sharov, A. A., Dudekula, D. B., VanBuren, V., & Ko, M. S. H. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh241 · Cited by 516 · see citing works
Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog
Rera, M., Bahadorani, S., Cho, J., Koehler, C. L., Ulgherait, M., Hur, J. H., Ansari, W. S., Lo, T., Jones, D. L., & Walker, D. W. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.09.013 · Cited by 472 · see citing works
Motif module map reveals enforcement of aging by continual NF-κB activity
Adler, A. S., Sinha, S., Kawahara, T. L. A., Zhang, J. Y., Segal, E., & Chang, H. Y. (2007) · Genes & Development · doi:10.1101/gad.1588507 · Cited by 466 · see citing works
A Developmental Timing MicroRNA and Its Target Regulate Life Span in C. elegans
Boehm, M., & Slack, F. J. (2005) · Science · doi:10.1126/science.1115596 · Cited by 449 · see citing works
AGEMAP: A Gene Expression Database for Aging in Mice
Zahn, J. M., Poosala, S., Owen, A. B., Ingram, D. K., Lustig, A., Carter, A., Weeraratna, A. T., Taub, D. D., Gorospe, M., Mazan-Mamczarz, K., et al. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030201 · Cited by 431 · see citing works
Wolfe, C. J., Kohane, I. S., & Butte, A. J. (2005) · BMC Bioinformatics · doi:10.1186/1471-2105-6-227 · Cited by 422 · see citing works
de la Fuente, A. (2010) · Trends in Genetics · doi:10.1016/j.tig.2010.05.001 · Cited by 420 · see citing works
Mitochondrial dysfunction in the pathophysiology of renal diseases
Che, R., Yuan, Y., Huang, S., & Zhang, A. (2013) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00571.2013 · Cited by 393 · see citing works
Aging increases cell-to-cell transcriptional variability upon immune stimulation
Martinez-Jimenez, C. P., Eling, N., Chen, H.-C., Vallejos, C. A., Kolodziejczyk, A. A., Connor, F., Stojic, L., Rayner, T. F., Stubbington, M. J. T., Teichmann, S. A., et al. (2017) · Science · doi:10.1126/science.aah4115 · Cited by 339 · see citing works
From signatures to models: understanding cancer using microarrays
Segal, E., Friedman, N., Kaminski, N., Regev, A., & Koller, D. (2005) · Nature Genetics · doi:10.1038/ng1561 · Cited by 380 · see citing works
Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging
Ziegler, D. V., Wiley, C. D., & Velarde, M. C. (2014) · Aging Cell · doi:10.1111/acel.12287 · Cited by 353 · see citing works
Aubin‐Horth, N., & Renn, S. C. P. (2009) · Molecular Ecology · doi:10.1111/j.1365-294x.2009.04313.x · Cited by 354 · see citing works
Transcriptional profiling of aging in human muscle reveals a common aging signature
Zahn, J. M., Sonu, R., Vogel, H., Crane, E., Mazan-Mamczarz, K., Rabkin, R., Davis, R. W., Becker, K. G., Owen, A. B., & Kim, S. K. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020115 · Cited by 351 · see citing works
Variation within and among species in gene expression: raw material for evolution
Whitehead, A., & Crawford, D. L. (2006) · Molecular Ecology · doi:10.1111/j.1365-294x.2006.02868.x · Cited by 341 · see citing works
A Transcriptional Profile of Aging in the Human Kidney
Rodwell, G. E. J., Sonu, R., Zahn, J. M., Lund, J., Wilhelmy, J., Wang, L., Xiao, W., Mindrinos, M., Crane, E., Segal, E., et al. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020427 · Cited by 338 · see citing works
Schroder, K., Irvine, K. M., Taylor, M. S., Bokil, N. J., Cao, K. L., Masterman, K., Labzin, L. I., Semple, C. A. M., Kapétanovic, R., Fairbairn, L., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110156109 · Cited by 305 · see citing works
Post-transcriptional control of gene expression: a genome-wide perspective
Mata, J., Marguerat, S., & Bähler, J. (2005) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.07.005 · Cited by 288 · see citing works
Conservation and evolvability in regulatory networks: The evolution of ribosomal regulation in yeast
Tanay, A., Regev, A., & Ron Shamir, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502521102 · Cited by 262 · see citing works
van der Pluijm, I., Garinis, G. A., Brandt, R. M. C., Gorgels, T. G. M. F., Wijnhoven, S., Diderich, K. E. M., de Wit, J., Mitchell, J. R., van Oostrom, C., Beems, R. B., et al. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0050002 · Cited by 237 · see citing works
Lockwood, B. L., Sanders, J. G., & Somero, G. N. (2010) · Journal of Experimental Biology · doi:10.1242/jeb.046094 · Cited by 238 · see citing works
Function-informed transcriptome analysis of Drosophila renal tubule
Wang, J., Kean, L., Yang, J., Allan, A. K., Davies, S. A., Herzyk, P., & Dow, J. A. T. (2004) · Genome biology · doi:10.1186/gb-2004-5-9-r69 · Cited by 224 · see citing works
Jiao, Y., Ma, L., Strickland, E., & Deng, X. W. (2005) · The Plant Cell · doi:10.1105/tpc.105.035840 · Cited by 213 · see citing works
Groh, K. J., Carvalho, R., Chipman, J. K., Denslow, N. D., Halder, M., Murphy, C. A., Roelofs, D., Rolaki, A., Schirmer, K., & Watanabe, K. H. (2014) · Chemosphere · doi:10.1016/j.chemosphere.2014.09.068 · Cited by 208 · see citing works
Self-citationWong, D., Bazopoulou, D., Pujol, N., Tavernarakis, N., & Ewbank, J. J. (2007) · Genome biology · doi:10.1186/gb-2007-8-9-r194 · Cited by 203 · see citing works
An evaluation of GO annotation retrieval for BioCreAtIvE and GOA
Camon, E. B., Barrell, D. G., Dimmer, E. C., Lee, V., Magrane, M., Maslen, J., Binns, D., & Apweiler, R. (2005) · BMC Bioinformatics · doi:10.1186/1471-2105-6-s1-s17 · Cited by 201 · see citing works
Genome-Wide Analysis of Rad52 Foci Reveals Diverse Mechanisms Impacting Recombination
Álvaro, D., Lisby, M., & Rothstein, R. J. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030228 · Cited by 198 · see citing works
Mitochondrial Dysfunction: The First Domino in Brain Aging and Alzheimer's Disease?
Leuner, K., Hauptmann, S., Abdel-Kader, R. M., Scherping, I., Keil, U., Strosznajder, J. B., Eckert, A., & Müller, W. E. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1763 · Cited by 194 · see citing works
The search for DAF-16/FOXO transcriptional targets: Approaches and discoveries
Murphy, C. T. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.06.040 · Cited by 189 · see citing works
Self-citationVawter, M. P., Tomita, H., Meng, F., Bolstad, B. M., Li, J., Evans, S. J., Choudary, P. V., Atz, M. E., Shao, L., Neal, C. R., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001830 · Cited by 181 · see citing works
microRNAs: small molecules with big roles –C. elegans to human cancer
Kato, M., & Slack, F. J. (2008) · Biology of the Cell · doi:10.1042/bc20070078 · Cited by 185 · see citing works
Conserved developmental transcriptomes in evolutionarily divergent species
Parikh, A., Miranda, E. R., Katoh‐Kurasawa, M., Fuller, D., Rot, G., Žagar, L., Curk, T., Sucgang, R., Chen, R., Zupan, B., et al. (2010) · Genome biology · doi:10.1186/gb-2010-11-3-r35 · Cited by 177 · see citing works
Gene expression hallmarks of cellular ageing
Frenk, S., & Houseley, J. M. (2018) · Biogerontology · doi:10.1007/s10522-018-9750-z · Cited by 180 · see citing works
Aging and Gene Expression in the Primate Brain
Fraser, H. B., Khaitovich, P., Plotkin, J. B., Pääbo, S., & Eisen, M. B. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030274 · Cited by 172 · see citing works
Transcriptional profiling of aging in human muscle reveals a common aging signature
Zahn, J. M., Sonu, R. J., Vogel, H. S., Crane, E., Mazan-Mamczarz, K., Rabkin, R., Davis, R. W., Becker, K. G., Owen, A. B., & Kim, S. K. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0020115.eor · Cited by 171 · see citing works
A modular network model of aging
Xue, H., Xian, B., Dong, D., Xia, K., Zhu, S., Zhang, Z., Hou, L., Zhang, Q., Zhang, Y., & Han, J. J. (2007) · Molecular Systems Biology · doi:10.1038/msb4100189 · Cited by 170 · see citing works
PGC-1α in aging and anti-aging interventions
Anderson, R., & Prolla, T. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.04.005 · Cited by 162 · see citing works
Gene expression in the brain and kidney of rainbow trout in response to handling stress
Krasnov, A., Koskinen, H., Pehkonen, P., Rexroad, C. E., Afanasyev, S., & Mölsä, H. (2005) · BMC Genomics · doi:10.1186/1471-2164-6-3 · Cited by 158 · see citing works
A systems view of mRNP biologyPreprint
Hieronymus, H., & Silver, P. A. (2004) · Genes & Development · doi:10.1101/gad.1256904 · Cited by 157 · see citing works
Lasky, J. R., Marais, D. L. D., Lowry, D. B., Povolotskaya, I., McKay, J., Richards, J. H., Keitt, T. H., & Juenger, T. (2014) · Molecular Biology and Evolution · doi:10.1093/molbev/msu170 · Cited by 155 · see citing works
Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans
Kato, M., Chen, X., Inukai, S., Zhao, H., & Slack, F. J. (2011) · RNA · doi:10.1261/rna.2714411 · Cited by 156 · see citing works
Combining Results of Microarray Experiments: A Rank Aggregation Approach
DeConde, R. P., Hawley, S. J., Falcon, S., Clegg, N. J., Knudsen, B. S., & Etzioni, R. (2006) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1204 · Cited by 154 · see citing works
Branched-chain amino acid catabolism is a conserved regulator of physiological ageing
Mansfeld, J., Urban, N., Priebe, S., Groth, M., Frahm, C., Hartmann, N., Gebauer, J., Ravichandran, M., Dommaschk, A., Schmeisser, S., et al. (2015) · Nature Communications · doi:10.1038/ncomms10043 · Cited by 149 · see citing works
Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs
Steegenga, W. T., Boekschoten, M. V., Lute, C., Hooiveld, G. J. E. J., de Groot, P. J., Morris, T. J., Teschendorff, A. E., Butcher, L. M., Beck, S., & Müller, M. M. (2014) · AGE · doi:10.1007/s11357-014-9648-x · Cited by 148 · see citing works
The end of “naïve reductionism”: rise of systems biology or renaissance of physiology?
Strange, K. B. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00598.2004 · Cited by 147 · see citing works
Programmatic features of aging originating in development: aging mechanisms beyond molecular damage?
de Magalhães, J. P. (2012) · The FASEB Journal · doi:10.1096/fj.12-210872 · Cited by 147 · see citing works
Transcriptional Signatures of Aging
Stegeman, R., & Weake, V. M. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.06.019 · Cited by 146 · see citing works
Karasik, D., Demissie, S., Cupples, L. A., & Kiel, D. P. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.5.574 · Cited by 144 · see citing works
Landis, G. N., Shen, J., & Tower, J. (2012) · Aging · doi:10.18632/aging.100499 · Cited by 142 · see citing works
He, Y., & Jasper, H. (2014) · Methods · doi:10.1016/j.ymeth.2014.04.008 · Cited by 140 · see citing works
Role of TOR signaling in aging and related biological processes in Drosophila melanogaster
Katewa, S. D., & Kapahi, P. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.11.036 · Cited by 134 · see citing works
Münch, D., Amdam, G. V., & Wolschin, F. (2008) · Functional Ecology · doi:10.1111/j.1365-2435.2008.01419.x · Cited by 134 · see citing works
Anne, S. L., Saudou, F., & Humbert, S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1831-07.2007 · Cited by 132 · see citing works
Curtis, C. N., Landis, G. N., Folk, D. G., Wehr, N. B., Hoe, N., Waskar, M., Abdueva, D. A., Skvortsov, D., Ford, D., Luu, A., et al. (2007) · Genome biology · doi:10.1186/gb-2007-8-12-r262 · Cited by 135 · see citing works
Cellular senescence links aging and diabetes in cardiovascular disease
Shakeri, H., Lemmens, K., Gevaert, A. B., De Meyer, G. R. Y., & Segers, V. F. M. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00287.2018 · Cited by 134 · see citing works
Carvallo-Pinto, M. A., Pino, M., Jeknić, Z., Zou, C., Doherty, C. J., Shiu, S., Chen, T. H. H., & Thomashow, M. F. (2011) · Journal of Experimental Botany · doi:10.1093/jxb/err066 · Cited by 132 · see citing works
Age-Related Changes in the Elastic Tissue of the Human Aorta
Fritze, O., Romero, B., Schleicher, M., Jacob, M. P., Oh, D., STARCHER, B. C., Schenke‐Layland, K., Buján, J., & Stock, U. A. (2011) · Journal of Vascular Research · doi:10.1159/000331278 · Cited by 132 · see citing works
Ihmels, J., Bergmann, S., Berman, J. G., & Barkai, N. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010039 · Cited by 131 · see citing works
Genomic evolution of the placenta using co-option and duplication and divergencePreprint
Knox, K., & Baker, J. C. (2008) · Genome Research · doi:10.1101/gr.071407.107 · Cited by 126 · see citing works
Cahan, P., Rovegno, F., Mooney, D. L., Newman, J. C., Laurent, G. S., & McCaffrey, T. A. (2007) · Gene · doi:10.1016/j.gene.2007.06.016 · Cited by 126 · see citing works
Perrino, C., Barabási, A.-Ĺ., Condorelli, G., Davidson, S. M., Windt, L. J. D., Dimmeler, S., Engel, F. B., Hausenloy, D. J., Hill, J. A., Laake, L. W. V., et al. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx070 · Cited by 125 · see citing works
Trimethylation of Lys36 on H3 restricts gene expression change during aging and impacts life spanPreprint
Pu, M., Ni, Z., Wang, M., Wang, X., Wood, J. G., Helfand, S. L., Yu, H., & Lee, S. S. (2015) · Genes & Development · doi:10.1101/gad.254144.114 · Cited by 123 · see citing works
A microarray analysis of the rice transcriptome and its comparison to ArabidopsisPreprint
Ma, L., Chen, C., Liu, X., Jiao, Y., Su, N., Li, L., Wang, X., Cao, M., Sun, N., Zhang, X., et al. (2005) · Genome Research · doi:10.1101/gr.3657405 · Cited by 122 · see citing works
Kabani, S., Fenn, K., Ross, A., Ivens, A. C., Smith, T., Ghazal, P., & Matthews, K. R. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-427 · Cited by 120 · see citing works
Genome-wide gene expression regulation as a function of genotype and age in C. elegans.Preprint
Viñuela, A., Snoek, L. B., Riksen, J., & Kammenga, J. (2010) · Genome Research · doi:10.1101/gr.102160.109 · Cited by 136 · see citing works
Integrating evolutionary and molecular genetics of aging
Flatt, T., & SCHMIDT, P. S. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.07.010 · Cited by 116 · see citing works
Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans
Meyer, J. N., Boyd, W. A., Azzam, G. A., Haugen, A. C., Freedman, J. H., & Houten, B. V. (2007) · Genome biology · doi:10.1186/gb-2007-8-5-r70 · Cited by 114 · see citing works
Specific age related signatures in Drosophila body parts transcriptome
Girardot, F., Lasbleiz, C., Monnier, V., & Tricoire, H. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-69 · Cited by 113 · see citing works
Comprehensive transcriptional landscape of aging mouse liver
White, R. R., Milholland, B., MacRae, S. L., Lin, M., Zheng, D., & Vijg, J. (2015) · BMC Genomics · doi:10.1186/s12864-015-2061-8 · Cited by 113 · see citing works
Sexual and Temporal Dynamics of Molecular Evolution in C. elegans Development
Cutter, A. D., & Ward, S. F. (2004) · Molecular Biology and Evolution · doi:10.1093/molbev/msh267 · Cited by 113 · see citing works
Mimetics of Caloric Restriction Include Agonists of Lipid-activated Nuclear Receptors
Corton, J. C., Apte, U. M., Anderson, S. P., Limaye, P. B., Yoon, L. W., Latendresse, J. R., Dunn, C. S., Everitt, J. I., Voss, K. A., Swanson, C. L., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406739200 · Cited by 113 · see citing works
Involvement of oxidatively damaged DNA and repair in cancer development and aging.
Tudek, B., Winczura, A., Janik, J., Siomek, A., Foksiński, M., & Oliński, R. (2010) · PubMed Central · Cited by 112 · see citing works
Extracting Gene Networks for Low-Dose Radiation Using Graph Theoretical Algorithms
Voy, B. H., Scharff, J. A., Perkins, A., Saxton, A. M., Borate, B. R., Chesler, E. J., Branstetter, L. R., & Langston, M. A. (2006) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020089 · Cited by 111 · see citing works
Interpreting physiological responses to environmental change through gene expression profiling
Gracey, A. Y. (2007) · Journal of Experimental Biology · doi:10.1242/jeb.004333 · Cited by 108 · see citing works
Age-dependent changes in mean and variance of gene expression across tissues in a twin cohort
Viñuela, A., Brown, A. A., Buil, A., Tsai, P.-C., Davies, M. N., Bell, J. T., Dermitzakis, E. T., Spector, T. D., & Small, K. S. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx424 · Cited by 114 · see citing works
Whitehead, A. (2012) · Journal of Experimental Biology · doi:10.1242/jeb.058735 · Cited by 108 · see citing works
DAF-16-Dependent Suppression of Immunity During Reproduction inCaenorhabditis elegans
Miyata, S., Begun, J., Troemel, E. R., & Ausubel, F. M. (2008) · Genetics · doi:10.1534/genetics.107.083923 · Cited by 108 · see citing works
Corton, J. C., & Brown-Borg, H. M. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.12.1494 · Cited by 106 · see citing works
Crabtree, J. S., Jelinsky, S. A., Harris, H. A., Choe, S. E., Cotreau, M. M., Kimberland, M. L., Wilson, E., Saraf, K. A., Liu, W., McCampbell, A. S., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4471 · Cited by 99 · see citing works
Oxidative damage to DNA and antioxidant status in aging and age-related diseases.
Oliński, R., Siomek, A., Różalski, R., Gackowski, D., Foksiński, M., Guz, J., Dziaman, T., Szpila, A., & Tudek, B. (2007) · Acta Biochimica Polonica · doi:10.18388/abp.2007_3265 · Cited by 102 · see citing works
Blalock, E. M., Chen, K.-C., Stromberg, A. J., Norris, C. M., Kadish, I., Kraner, S. D., Porter, N. M., & Landfield, P. W. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2005.06.006 · Cited by 103 · see citing works
Xian, B., Shen, J., Chen, W., Sun, N., Qiao, N., Jiang, D., Yu, T., Men, Y., Han, Z., Pang, Y., et al. (2013) · Aging Cell · doi:10.1111/acel.12063 · Cited by 102 · see citing works
MicroRNAs and the Genetic Network in Aging
Inukai, S., & Slack, F. J. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.01.023 · Cited by 99 · see citing works
Transcriptional response to aging and caloric restriction in heart and adipose tissue
Linford, N. J., Beyer, R. P., Gollahon, K. A., Krajcik, R. A., Malloy, V. L., Demas, V., Burmer, G. C., & Rabinovitch, P. S. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00319.x · Cited by 100 · see citing works
Reversal of aging by NFκB blockade
Adler, A. S., Kawahara, T. L. A., Segal, E., & Chang, H. Y. (2008) · Cell Cycle · doi:10.4161/cc.7.5.5490 · Cited by 99 · see citing works
A forkhead in the road to longevity: the molecular basis of lifespan becomes clearer
Morris, B. J. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000173509.45363.dd · Cited by 98 · see citing works
Common aging pathways in worms, flies, mice and humans
Kim, S. K. (2007) · Journal of Experimental Biology · doi:10.1242/jeb.004887 · Cited by 98 · see citing works
Kučerová, L., Kubrak, O. I., Bengtsson, J., Strnad, H., Nylin, S., Theopold, U., & Nässel, D. R. (2016) · BMC Genomics · doi:10.1186/s12864-016-2383-1 · Cited by 97 · see citing works
- Authors
- McCarroll, S. A., Murphy, C. T., Zou, S., Pletcher, S. D., Chin, C.-S., Jan, Y. N., Kenyon, C., Bargmann, C. I., & Li, H.
- Affiliations
- University of California, San Francisco (US)
- University College London (GB)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Li, Hao
- ORCID
- Venue
- Nature Genetics
- Published
- 2004-01-18
- Volume
- 36
- Issue
- 2
- Pages
- 197-204
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2118852675
- Cited by
- 454
- References
- 51
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 8 · 2021: 28 · 2020: 15 · 2019: 13 · 2018: 15 · 2017: 15 · 2016: 16 · 2015: 15 · 2014: 17 · 2013: 12 · 2012: 29
- FWCI
- 14.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Consorzio Interuniversitario Biotecnologie
- National Institute on Deafness and Other Communication Disorders
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- gene expression comparison, orthologs, aging, gene expression signatures, Gene Ontology, Caenorhabditis elegans, Drosophila melanogaster, mitochondrial metabolism, DNA repair, larval development, embryonic development, gametogenesis, mRNA degradation
- MeSH terms
- Age Factors, Aging, Animals, Drosophila melanogaster, Gene Expression Regulation, Humans, Phylogeny, Saccharomyces cerevisiae, Time Factors, Caenorhabditis elegans, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic
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