Flies selected for longevity retain a young gene expression profile

Springer Science and Business Media LLC - Tập 33 - Trang 69-80 - 2010
Pernille Sarup1, Peter Sørensen2, Volker Loeschcke1
1Aarhus Centre for Environmental Stress Research (ACES), Department of Biological Sciences, Aarhus University, Aarhus C, Denmark
2Department of Genetics and Biotechnology, Danish Institute of Agricultural Sciences, Aarhus University, Tjele, Denmark

Tóm tắt

We investigated correlated responses in the transcriptomes of longevity-selected lines of Drosophila melanogaster to identify pathways that affect life span in metazoan systems. We evaluated the gene expression profile in young, middle-aged, and old male flies, finding that 530 genes were differentially expressed between selected and control flies when measured at the same chronological age. The longevity-selected flies consistently showed expression profiles more similar to control flies one age class younger than control flies of the same age. This finding is in accordance with a younger gene expression profile in longevity-selected lines. Among the genes down-regulated in longevity-selected lines, we found a clear over-representation of genes involved in immune functions, supporting the hypothesis of a life-shortening effect of an overactive immune system, known as inflammaging. We judged the physiological age as the level of cumulative mortality. Eighty-four genes were differentially expressed between the control and longevity-selected lines at the same physiological age, and the overlap between the same chronological and physiological age gene lists included 40 candidate genes for increased longevity. Among these candidates were genes with roles in starvation resistance, immune response regulation, and several that have not yet been linked to longevity. Investigating these genes would provide new knowledge of the pathways that affect life span in invertebrates and, potentially, mammals.

Tài liệu tham khảo

Arking R, Dudas SP (1989) Review of genetic investigations into the aging processes of Drosophila. J Am Geriatr Soc 37:757–773 Ayroles JF, Carbone MA, Stone EA, Jordan KW, Lyman RF, Magwire MM, Rollmann SM, Duncan LH, Lawrence F, Anholt RRH, Mackay TFC (2009) Systems genetics of complex traits in Drosophila melanogaster. Nat Genet 41:299–307. doi:10.1038/ng.332 Baldal EA, Brakefield PM, Zwaan BJ (2006) Multitrait evolution in lines of Drosophila melanogaster selected for increased starvation resistance: the role of metabolic rate and implications for the evolution of longevity. Evolution 60:1435–1444 Bubliy OA, Loeschcke V (2005) Correlated responses to selection for stress resistance and longevity in a laboratory population of Drosophila melanogaster. J Evol Biol 18:789–803. doi:10.1111/j.1420-9101.2005.00928.x Curtis C, Landis GN, Folk D, Wehr NB, Hoe N, Waskar M, Abdueva D, Skvortsov D, Ford D, Luu A, Badrinath A, Levine RL, Bradley TJ, Tavare S, Tower J (2007) Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes. Genome Biol 8(12):R262 Dennis G, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4, doi:R60 Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panouraia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2006) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105. doi:10.1016/j.mad.2006.11.016 Girardot F, Lasbleiz C, Monnier V, Tricoire H (2006) Specific age related signatures in Drosophila body parts transcriptome. BMC Genomics 7, doi:6910.1186/1471-2164-7-69 Golden TR, Hubbard A, Melov S (2006) Microarray analysis of variation in individual aging C. elegans: approaches and challenges. Exp Gerontol 41:1040–1045. doi:10.1016/j.exger.2006.06.034 Grotewiel MS, Martin I, Bhandari P, Cook-Wiens E (2005) Functional senescence in Drosophila melanogaster. Ageing Res Rev 4:372–397. doi:10.1016/j.arr.2005.04.001 Hamilton WD (1966) Moulding of senescence by natural selection. J Theor Biol 12:12–45 Harbison ST, Chang S, Kamdar KP, Mackay TFC (2005) Quantitative genomics of starvation stress resistance in Drosophila. Genome Biol 6:15. doi:10.1186/gb-2005-6-4-r36 Hercus MJ, Hoffmann AA (2000) Maternal and grandmaternal age influence offspring fitness in Drosophila. Proc R Soc Lond Ser B-Biol Sci 267:2105–2110 Hoffmann AA, Dagher H, Hercus M, Berrigan D (1997) Comparing different measures of heat resistance in selected lines of Drosophila melanogaster. J Insect Physiol 43:393–405 Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP (2003) Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 4:249–264 Jazwinski SM (1996) Longevity, genes, and aging. Science 273:54–59 Kim SN, Rhee JH, Song YH, Park DY, Hwang M, Lee SI, Kim JE, Gim BS, Yoon JH, Kim YJ, Kim-Ha J (2005) Age-dependent changes of gene expression in the Drosophila head. Neurobiol Aging 26:1083–1091. doi:10.1016/j.neurobiolaging.2004.06.017 Kirkwood TBL (1977) Evolution of aging. Nature 270:301–304 Kirkwood TBL, Feder M, Finch CE, Franceschi C, Globerson A, Klingenberg CP, LaMarco K, Omholt S, Westendorp RGJ (2005) What accounts for the wide variation in life span of genetically identical organisms reared in a constant environment? Mech. Ageing Devel 126:439–443. doi:10.1016/j.mad.2004.09.008 Klass M, Hirsh D (1976) Non-aging developmental variant of Caenorhabditis elegans. Nature 260:523–525 Kristensen TN, Sørensen P, Kruhoffer M, Pedersen KS, Loeschcke V (2005) Genome-wide analysis on inbreeding effects on gene expression in Drosophila melanogaster. Genetics 171:157–167. doi:10.1534/genetics.104.039610 Landis GN, Abdueva D, Skvortsov D, Yang JD, Rabin BE, Carrick J, Tavare S, Tower J (2004) Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster. Proc Natl Acad Sci USA 101:7663–7668. doi:10.1073/pnas.0307605101 Lithgow GJ (1996) Invertebrate gerontology: the age mutations of Caenorhabditis elegans. Bioessays 18:809–815 Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429:883–891. doi:10.1038/nature02661 Luckinbill LS, Arking R, Clare MJ, Cirocco WC, Buck SA (1984) Selection for delayed senescence in Drosophila melanogaster. Evolution 38:996–1003 Lund J, Tedesco P, Duke K, Wang J, Kim SK, Johnson TE (2002) Transcriptional profile of aging in C. elegans. Curr Biol 12:1566–1573 Medaware PB (1952) An unsolved problem in biology. K.H. Lewis, London Oudman L, Van Delden W, Kamping A, Bijlsma R (1994) Starvation resistance in Drosophila melanogaster in relation to the polymorphisms at the adh and alpha-gpdh loci. J Insect Physiol 40:709–713 Partridge L (2009) Some highlights of research on aging with invertebrates, 2009. Aging Cell 8:509–513. doi:10.1111/j.1474-9726.2009.00498.x Pearl R, Parker SL, Gonzalez BM (1923) Experimental studies on the duration of life VII. The Mendelian inheritance of duration of life in crosses of wild type and quintuple stocks of Drosophila melanogaster. Am Nat 57:153–192 Pletcher SD, Libert S, Skorupa D (2005) Flies and their golden apples: the effect of dietary restriction on Drosophila aging and age-dependent gene expression. Ageing Res Rev 4:451–480. doi:10.1016/j.arr.2005.06.007 Promislow DEL, Tatar M, Pletcher S, Carey JR (1999) Below threshold mortality: implications for studies in evolution, ecology and demography. J Evol Biol 12:314–328 Redden DT, Fernandez JR, Allison DB (2004) A simple significance test for quantile regression. Stat Med 23:2587–2597. doi:10.1002/sim.1839 Rodwell GEJ, Sonu R, Zahn JM, Lund J, Wilhelmy J, Wang LL, Xiao WZ, Mindrinos M, Crane E, Segal E, Myers BD, Brooks JD, Davis RW, Higgins J, Owen AB, Kim SK (2004) A transcriptional profile of aging in the human kidney. Nature 2:2191–2201. doi:10.1371/journal.pbio.0020427 Service PM (1989) The effect of mating status on lifespan, egg-laying, and starvation resistance in Drosophila melanogaster in relation to selection on longevity. J Insect Physiol 35:447–452 Smyth GK (2005) Limma: linear models for microarray data. In: Gentleman R, Carey V, Dudoit S, Irizarry R, Huber W (eds) Bioinformatics and computational biology solutions using R and bioconductor. Springer, New York Sørensen JG, Nielsen MM, Kruhoffer M, Justesen J, Loeschcke V (2005) Full genome gene expression analysis of the heat stress response, in Drosophila melanogaster. Cell Stress Chaperones 10:312–328 Sørensen JG, Nielsen MM, Loeschcke V (2007) Gene expression profile analysis of Drosophila melanogaster selected for resistance to environmental stressors. J Evol Biol 20:1624–1636. doi:10.1111/j.1420-9101.2007.01326.x Strehler BL (1961) Studies on the comparative physiology of aging. 2. On the mechanism of temperature life-shortening in Drosophila melanogaster. J Gerontol 16:2–12 Tarnopolsky M, Phillips S, Parise G, Varbanov A, DeMuth J, Stevens P, Qu A, Wang F, Isfort R (2007) Gene expression, fiber type, and strength are similar between left and right legs in older adults. J Gerontol Ser A-Biol Sci Med Sci 62:1088–1095 Wang CX, Li Q, Redden DT, Weindruch R, Allison DB (2004) Statistical methods for testing effects on "maximum lifespan". Mech Ageing Dev 125:629–632. doi:10.1016/j.mad.2004.07.003 Watson MJO, Hoffmann AA (1996) Acclimation, cross-generation effects, and the response to selection for increased cold resistance in Drosophila. Evolution 50:1182–1192 Williams GC (1957) Pleiotropy, natural-selection, and the evolution of senescence. Evolution 11:398–411 Zahn JM, Sonu R, Vogel H, Crane E, Mazan-Mamczarz K, Rabkin R, Davis RW, Becker KG, Owen AB, Kim SK (2006) Transcriptional profiling of aging in human muscle reveals a common aging signature. PLoS Genet 2:1058–1069. doi:e11510.1371/journal.pgen.0020115 Zerofsky M, Harel E, Silverman N, Tatar M (2005) Aging of the innate immune response in Drosophila melanogaster. Aging Cell 4:103–108. doi:10.1111/j.1474-9728.2005.00147.x Zwaan B, Bijlsma R, Hoekstra RE (1995) Direct selection on life-span in Drosophila melanogaster. Evolution 49:649–659