Specific age related signatures in Drosophila body parts transcriptome
Tóm tắt
During the last two decades progress in the genetics of aging in invertebrate models such as C. elegans and D. melanogaster has clearly demonstrated the existence of regulatory pathways that control the rate of aging in these organisms, such as the insulin-like pathway, the Jun kinase pathway and the Sir2 deacetylase pathway. Moreover, it was rapidly shown that some of these pathways are conserved from yeast to humans. In parallel to genetic studies, genomic expression approches have given us significant information on the gene expression modifications that occur during aging either in wild type or long-lived mutant animals. But most of the genomic studies of invertebrate models have been performed so far on whole animals, while several recent studies in mammals have shown that the effects of aging are tissue specific. We used oligonucleotide microarrays to address the specificities of transcriptional responses in aging Drosophila in head, thorax or whole body. These fly parts are enriched in transcripts that represent different and complementary sets of genes. We present evidence for both specific and common transcriptional responses during the aging process in these tissues. About half of the genes described as downregulated with age are linked to reproduction and enriched in gonads. Greater downregulation of mitochondrial genes, activation of the JNK pathway and upregulation of proteasome subunits in the thorax of aged flies all suggest that muscle may be particularly sensitive to aging. Simultaneous age-related impairment of synaptic transmission gene expression is observed in fly heads. In addition, a detailed comparison with other microarray data indicates that in aged flies there are significant deviations from the canonical responses to oxidative stress and immune stress. Our data demonstrates the advantages and value of regionalized and comparative analysis of gene expression in aging animals. Adding to the age-regulated genes already identified in whole animal studies, it provides lists of new regionalized genes to be studied for their functional role in the aging process. This work also emphasizes the need for such experiments to reveal in greater detail the consequences of the transcriptional modifications induced by aging regulatory pathways.
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citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands; citation_author=SJ Broughton, MD Piper, T Ikeya, TM Bass, J Jacobson, Y Driege, P Martinez, E Hafen, DJ Withers, SJ Leevers, L Partridge; citation_volume=102; citation_publication_date=2005; citation_pages=3105-3110; citation_doi=10.1073/pnas.0405775102; citation_id=CR1
citation_journal_title=Science; citation_title=Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein; citation_author=DJ Clancy, D Gems, LG Harshman, S Oldham, H Stocker, E Hafen, SJ Leevers, L Partridge; citation_volume=292; citation_publication_date=2001; citation_pages=104-106; citation_doi=10.1126/science.1057991; citation_id=CR2
citation_journal_title=Annu Rev Genomics Hum Genet; citation_title=The genetics of aging; citation_author=CE Finch, G Ruvkun; citation_volume=2; citation_publication_date=2001; citation_pages=435-462; citation_doi=10.1146/annurev.genom.2.1.435; citation_id=CR3
citation_journal_title=Nature; citation_title=Genetic pathways that regulate ageing in model organisms; citation_author=L Guarente, C Kenyon; citation_volume=408; citation_publication_date=2000; citation_pages=255-262; citation_doi=10.1038/35041700; citation_id=CR4
citation_journal_title=Mech Ageing Dev; citation_title=Calorie restriction and SIR2 genes--towards a mechanism; citation_author=L Guarente; citation_volume=126; citation_publication_date=2005; citation_pages=923-928; citation_doi=10.1016/j.mad.2005.03.013; citation_id=CR5
citation_journal_title=Science; citation_title=Genetics and the specificity of the aging process; citation_author=S Hekimi, L Guarente; citation_volume=299; citation_publication_date=2003; citation_pages=1351-1354; citation_doi=10.1126/science.1082358; citation_id=CR6
citation_journal_title=Nature; citation_title=Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body; citation_author=DS Hwangbo, B Gershman, MP Tu, M Palmer, M Tatar; citation_volume=429; citation_publication_date=2004; citation_pages=562-566; citation_doi=10.1038/nature02549; citation_id=CR7
citation_journal_title=Cell; citation_title=The plasticity of aging: insights from long-lived mutants; citation_author=C Kenyon; citation_volume=120; citation_publication_date=2005; citation_pages=449-460; citation_doi=10.1016/j.cell.2005.02.002; citation_id=CR8
citation_journal_title=Science; citation_title=Extended life-span and stress resistance in the Drosophila mutant methuselah; citation_author=YJ Lin, L Seroude, S Benzer; citation_volume=282; citation_publication_date=1998; citation_pages=943-946; citation_doi=10.1126/science.282.5390.943; citation_id=CR9
citation_journal_title=Nat Genet; citation_title=Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling; citation_author=K Lin, H Hsin, N Libina, C Kenyon; citation_volume=28; citation_publication_date=2001; citation_pages=139-145; citation_doi=10.1038/88850; citation_id=CR10
citation_journal_title=Exp Gerontol; citation_title=The neuroendocrine regulation of Drosophila aging; citation_author=M Tatar; citation_volume=39; citation_publication_date=2004; citation_pages=1745-1750; citation_doi=10.1016/j.exger.2004.06.024; citation_id=CR11
citation_journal_title=Dev Cell; citation_title=JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila; citation_author=MC Wang, D Bohmann, H Jasper; citation_volume=5; citation_publication_date=2003; citation_pages=811-816; citation_doi=10.1016/S1534-5807(03)00323-X; citation_id=CR12
citation_journal_title=Cell; citation_title=JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling; citation_author=MC Wang, D Bohmann, H Jasper; citation_volume=121; citation_publication_date=2005; citation_pages=115-125; citation_doi=10.1016/j.cell.2005.02.030; citation_id=CR13
citation_journal_title=Science; citation_title=Regulation of C. elegans life-span by insulinlike signaling in the nervous system; citation_author=CA Wolkow, KD Kimura, MS Lee, G Ruvkun; citation_volume=290; citation_publication_date=2000; citation_pages=147-150; citation_doi=10.1126/science.290.5489.147; citation_id=CR14
citation_journal_title=Science; citation_title=DAF-16 target genes that control C. elegans life-span and metabolism; citation_author=SS Lee, S Kennedy, AC Tolonen, G Ruvkun; citation_volume=300; citation_publication_date=2003; citation_pages=644-647; citation_doi=10.1126/science.1083614; citation_id=CR15
citation_journal_title=Nat Genet; citation_title=Comparing genomic expression patterns across species identifies shared transcriptional profile in aging; citation_author=SA McCarroll, CT Murphy, S Zou, SD Pletcher, CS Chin, YN Jan, C Kenyon, CI Bargmann, H Li; citation_volume=36; citation_publication_date=2004; citation_pages=197-204; citation_doi=10.1038/ng1291; citation_id=CR16
citation_journal_title=Nature; citation_title=Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans; citation_author=CT Murphy, SA McCarroll, CI Bargmann, A Fraser, RS Kamath, J Ahringer, H Li, C Kenyon; citation_volume=424; citation_publication_date=2003; citation_pages=277-283; citation_doi=10.1038/nature01789; citation_id=CR17
citation_journal_title=Nat Genet; citation_title=A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity; citation_author=SS Lee, RY Lee, AG Fraser, RS Kamath, J Ahringer, G Ruvkun; citation_volume=33; citation_publication_date=2003; citation_pages=40-48; citation_doi=10.1038/ng1056; citation_id=CR18
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys; citation_author=T Kayo, DB Allison, R Weindruch, TA Prolla; citation_volume=98; citation_publication_date=2001; citation_pages=5093-5098; citation_doi=10.1073/pnas.081061898; citation_id=CR19
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Genomic profiling of short- and long-term caloric restriction effects in the liver of aging mice; citation_author=SX Cao, JM Dhahbi, PL Mote, SR Spindler; citation_volume=98; citation_publication_date=2001; citation_pages=10630-10635; citation_doi=10.1073/pnas.191313598; citation_id=CR20
citation_journal_title=Nat Genet; citation_title=Gene-expression profile of the ageing brain in mice; citation_author=CK Lee, R Weindruch, TA Prolla; citation_volume=25; citation_publication_date=2000; citation_pages=294-297; citation_doi=10.1038/77046; citation_id=CR21
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts; citation_author=CK Lee, DB Allison, J Brand, R Weindruch, TA Prolla; citation_volume=99; citation_publication_date=2002; citation_pages=14988-14993; citation_doi=10.1073/pnas.232308999; citation_id=CR22
citation_journal_title=Physiol Genomics; citation_title=Transcriptional profiling identifies extensive downregulation of extracellular matrix gene expression in sarcopenic rat soleus muscle; citation_author=JS Pattison, LC Folk, RW Madsen, TE Childs, FW Booth; citation_volume=15; citation_publication_date=2003; citation_pages=34-43; citation_doi=10.1152/physiolgenomics.00040.2003; citation_id=CR23
citation_journal_title=Physiol Genomics; citation_title=Gene expression profile of aging in human muscle; citation_author=S Welle, AI Brooks, JM Delehanty, N Needler, CA Thornton; citation_volume=14; citation_publication_date=2003; citation_pages=149-159; citation_doi=10.1152/physiolgenomics.00049.2003; citation_id=CR24
citation_journal_title=Cardiovasc Res; citation_title=Gene expression profiling studies of aging in cardiac and skeletal muscles; citation_author=SK Park, TA Prolla; citation_volume=66; citation_publication_date=2005; citation_pages=205-212; citation_doi=10.1016/j.cardiores.2005.01.005; citation_id=CR25
citation_journal_title=Neurobiol Aging; citation_title=Age-dependent changes of gene expression in the Drosophila head; citation_author=SN Kim, JH Rhee, YH Song, DY Park, M Hwang, SL Lee, JE Kim, BS Gim, JH Yoon, YJ Kim, J Kim-Ha; citation_volume=26; citation_publication_date=2005; citation_pages=1083-1091; citation_doi=10.1016/j.neurobiolaging.2004.06.017; citation_id=CR26
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster; citation_author=GN Landis, D Abdueva, D Skvortsov, J Yang, BE Rabin, J Carrick, S Tavare, J Tower; citation_volume=101; citation_publication_date=2004; citation_pages=7663-7668; citation_doi=10.1073/pnas.0307605101; citation_id=CR27
citation_journal_title=Curr Biol; citation_title=Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster; citation_author=SD Pletcher, SJ Macdonald, R Marguerie, U Certa, SC Stearns, DB Goldstein, L Partridge; citation_volume=12; citation_publication_date=2002; citation_pages=712-723; citation_doi=10.1016/S0960-9822(02)00808-4; citation_id=CR28
citation_journal_title=Genome Biol; citation_title=A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults; citation_author=M Parisi, R Nuttall, P Edwards, J Minor, D Naiman, J Lu, M Doctolero, M Vainer, C Chan, J Malley, S Eastman, B Oliver; citation_volume=5; citation_publication_date=2004; citation_pages=R40; citation_doi=10.1186/gb-2004-5-6-r40; citation_id=CR29
citation_journal_title=BMC Genomics; citation_title=Genome wide analysis of common and specific stress responses in adult drosophila melanogaster; citation_author=F Girardot, V Monnier, H Tricoire; citation_volume=5; citation_publication_date=2004; citation_pages=74; citation_doi=10.1186/1471-2164-5-74; citation_id=CR30
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Genome-wide study of aging and oxidative stress response in Drosophila melanogaster; citation_author=S Zou, S Meadows, L Sharp, LY Jan, YN Jan; citation_volume=97; citation_publication_date=2000; citation_pages=13726-13731; citation_doi=10.1073/pnas.260496697; citation_id=CR31
citation_journal_title=Dev Cell; citation_title=Sequential activation of signaling pathways during innate immune responses in Drosophila; citation_author=M Boutros, H Agaisse, N Perrimon; citation_volume=3; citation_publication_date=2002; citation_pages=711-722; citation_doi=10.1016/S1534-5807(02)00325-8; citation_id=CR32
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays; citation_author=E De Gregorio, PT Spellman, GM Rubin, B Lemaitre; citation_volume=98; citation_publication_date=2001; citation_pages=12590-12595; citation_doi=10.1073/pnas.221458698; citation_id=CR33
citation_journal_title=Embo J; citation_title=The Toll and Imd pathways are the major regulators of the immune response in Drosophila; citation_author=E De Gregorio, PT Spellman, P Tzou, GM Rubin, B Lemaitre; citation_volume=21; citation_publication_date=2002; citation_pages=2568-2579; citation_doi=10.1093/emboj/21.11.2568; citation_id=CR34
citation_journal_title=Dev Cell; citation_title=The genomic response of the Drosophila embryo to JNK signaling; citation_author=H Jasper, V Benes, C Schwager, S Sauer, S Clauder-Munster, W Ansorge, D Bohmann; citation_volume=1; citation_publication_date=2001; citation_pages=579-586; citation_doi=10.1016/S1534-5807(01)00045-4; citation_id=CR35
citation_journal_title=Neuron; citation_title=A genome-wide search for synaptic vesicle cycle proteins in Drosophila; citation_author=TE Lloyd, P Verstreken, EJ Ostrin, A Phillippi, O Lichtarge, HJ Bellen; citation_volume=26; citation_publication_date=2000; citation_pages=45-50; citation_doi=10.1016/S0896-6273(00)81136-8; citation_id=CR36
citation_journal_title=Development; citation_title=A new family of growth factors produced by the fat body and active on Drosophila imaginal disc cells; citation_author=K Kawamura, T Shibata, O Saget, D Peel, PJ Bryant; citation_volume=126; citation_publication_date=1999; citation_pages=211-219; citation_id=CR37
citation_journal_title=Biochem J; citation_title=Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster; citation_author=M Ferguson, RJ Mockett, Y Shen, WC Orr, RS Sohal; citation_volume=390; citation_publication_date=2005; citation_pages=501-511; citation_doi=10.1042/BJ20042130; citation_id=CR38
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Mitochondrial "swirls" induced by oxygen stress and in the Drosophila mutant hyperswirl; citation_author=DW Walker, S Benzer; citation_volume=101; citation_publication_date=2004; citation_pages=10290-10295; citation_doi=10.1073/pnas.0403767101; citation_id=CR39
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Muscle-specific expression of Drosophila hsp70 in response to aging and oxidative stress; citation_author=JC Wheeler, ET Bieschke, J Tower; citation_volume=92; citation_publication_date=1995; citation_pages=10408-10412; citation_doi=10.1073/pnas.92.22.10408; citation_id=CR40
citation_journal_title=Nature; citation_title=Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans; citation_author=LA Herndon, PJ Schmeissner, JM Dudaronek, PA Brown, KM Listner, Y Sakano, MC Paupard, DH Hall, M Driscoll; citation_volume=419; citation_publication_date=2002; citation_pages=808-814; citation_doi=10.1038/nature01135; citation_id=CR41
citation_journal_title=Arch Biochem Biophys; citation_title=Altered proteasome function and subunit composition in aged muscle; citation_author=AD Husom, EA Peters, EA Kolling, NA Fugere, LV Thompson, DA Ferrington; citation_volume=421; citation_publication_date=2004; citation_pages=67-76; citation_doi=10.1016/j.abb.2003.10.010; citation_id=CR42
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Differential patterns of apoptosis in response to aging in Drosophila; citation_author=J Zheng, SW Edelman, G Tharmarajah, DW Walker, SD Pletcher, L Seroude; citation_volume=102; citation_publication_date=2005; citation_pages=12083-12088; citation_doi=10.1073/pnas.0503374102; citation_id=CR43
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=A mechanism of paraquat toxicity involving nitric oxide synthase; citation_author=BJ Day, M Patel, L Calavetta, LY Chang, JS Stamler; citation_volume=96; citation_publication_date=1999; citation_pages=12760-12765; citation_doi=10.1073/pnas.96.22.12760; citation_id=CR44
citation_journal_title=Aging Cell; citation_title=Aging of the innate immune response in Drosophila melanogaster; citation_author=M Zerofsky, E Harel, N Silverman, M Tatar; citation_volume=4; citation_publication_date=2005; citation_pages=103-108; citation_doi=10.1111/j.1474-9728.2005.00147.x; citation_id=CR45
citation_journal_title=Genes Dev; citation_title=Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila; citation_author=JM Park, H Brady, MG Ruocco, H Sun, D Williams, SJ Lee, TJ Kato, N Richards, K Chan, F Mercurio, M Karin, SA Wasserman; citation_volume=18; citation_publication_date=2004; citation_pages=584-594; citation_doi=10.1101/gad.1168104; citation_id=CR46
citation_journal_title=Nat Immunol; citation_title=Downregulation of lipopolysaccharide response in Drosophila by negative crosstalk between the AP1 and NF-kappaB signaling modules; citation_author=T Kim, J Yoon, H Cho, WB Lee, J Kim, YH Song, SN Kim, JH Yoon, J Kim-Ha, YJ Kim; citation_volume=6; citation_publication_date=2005; citation_pages=211-218; citation_doi=10.1038/ni1159; citation_id=CR47
citation_journal_title=Bioinformatics; citation_title=affy--analysis of Affymetrix GeneChip data at the probe level; citation_author=L Gautier, L Cope, BM Bolstad, RA Irizarry; citation_volume=20; citation_publication_date=2004; citation_pages=307-315; citation_doi=10.1093/bioinformatics/btg405; citation_id=CR48
citation_journal_title=Genome Biol; citation_title=Bioconductor: open software development for computational biology and bioinformatics; citation_author=RC Gentleman, VJ Carey, DM Bates, B Bolstad, M Dettling, S Dudoit, B Ellis, L Gautier, Y Ge, J Gentry, K Hornik, T Hothorn, W Huber, S Iacus, R Irizarry, F Leisch, C Li, M Maechler, AJ Rossini, G Sawitzki, C Smith, G Smyth, L Tierney, JY Yang, J Zhang; citation_volume=5; citation_publication_date=2004; citation_pages=R80; citation_doi=10.1186/gb-2004-5-10-r80; citation_id=CR49
citation_journal_title=Nucleic Acids Res; citation_title=Summaries of Affymetrix GeneChip probe level data; citation_author=RA Irizarry, BM Bolstad, F Collin, LM Cope, B Hobbs, TP Speed; citation_volume=31; citation_publication_date=2003; citation_pages=e15; citation_doi=10.1093/nar/gng015; citation_id=CR50
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=Significance analysis of microarrays applied to the ionizing radiation response; citation_author=VG Tusher, R Tibshirani, G Chu; citation_volume=98; citation_publication_date=2001; citation_pages=5116-5121; citation_doi=10.1073/pnas.091062498; citation_id=CR51