Genetic and metabolomic architecture of variation in diet restriction-mediated lifespan extension in Drosophila


Autoři: Kelly Jin aff001;  Kenneth A. Wilson aff002;  Jennifer N. Beck aff002;  Christopher S. Nelson aff002;  George W. Brownridge, III aff002;  Benjamin R. Harrison aff001;  Danijel Djukovic aff005;  Daniel Raftery aff005;  Rachel B. Brem aff002;  Shiqing Yu aff007;  Mathias Drton aff008;  Ali Shojaie aff009;  Pankaj Kapahi aff002;  Daniel Promislow aff001
Působiště autorů: Department of Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America aff001;  Buck Institute for Research on Aging, Novato, California, United States of America aff002;  Davis School of Gerontology, University of Southern California, University Park, Los Angeles, California, United States of America aff003;  Dominican University of California, San Rafael, California, United States of America aff004;  Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Washington, United States of America aff005;  Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, United States of America aff006;  Department of Statistics, University of Washington, Seattle, Washington, United States of America aff007;  Department of Mathematics, Technical University of Munich, Munich, Germany aff008;  Department of Biostatistics, University of Washington, Seattle, Washington, United States of America aff009;  Department of Biology, University of Washington, Seattle, Washington, United States of America aff010
Vyšlo v časopise: Genetic and metabolomic architecture of variation in diet restriction-mediated lifespan extension in Drosophila. PLoS Genet 16(7): e1008835. doi:10.1371/journal.pgen.1008835
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008835

Souhrn

In most organisms, dietary restriction (DR) increases lifespan. However, several studies have found that genotypes within the same species vary widely in how they respond to DR. To explore the mechanisms underlying this variation, we exposed 178 inbred Drosophila melanogaster lines to a DR or ad libitum (AL) diet, and measured a panel of 105 metabolites under both diets. Twenty four out of 105 metabolites were associated with the magnitude of the lifespan response. These included proteinogenic amino acids and metabolites involved in α-ketoglutarate (α-KG)/glutamine metabolism. We confirm the role of α-KG/glutamine synthesis pathways in the DR response through genetic manipulations. We used covariance network analysis to investigate diet-dependent interactions between metabolites, identifying the essential amino acids threonine and arginine as “hub” metabolites in the DR response. Finally, we employ a novel metabolic and genetic bipartite network analysis to reveal multiple genes that influence DR lifespan response, some of which have not previously been implicated in DR regulation. One of these is CCHa2R, a gene that encodes a neuropeptide receptor that influences satiety response and insulin signaling. Across the lines, variation in an intronic single nucleotide variant of CCHa2R correlated with variation in levels of five metabolites, all of which in turn were correlated with DR lifespan response. Inhibition of adult CCHa2R expression extended DR lifespan of flies, confirming the role of CCHa2R in lifespan response. These results provide support for the power of combined genomic and metabolomic analysis to identify key pathways underlying variation in this complex quantitative trait.

Klíčová slova:

Diet – Drosophila melanogaster – Genome-wide association studies – Metabolic networks – Metabolic pathways – Metabolites – Metabolomics – RNA interference


Zdroje

1. Kirkwood TB, Feder M, Finch CE, Franceschi C, Globerson A, Klingenberg CP, et al. What accounts for the wide variation in life span of genetically identical organisms reared in a constant environment? Mech Ageing Dev. 2005;126(3):439–43. doi: 10.1016/j.mad.2004.09.008 15664632.

2. Rea SL, Wu D, Cypser JR, Vaupel JW, Johnson TE. A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet. 2005;37(8):894–8. doi: 10.1038/ng1608 16041374; PubMed Central PMCID: PMC1479894.

3. Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015;161(1):106–18. doi: 10.1016/j.cell.2015.02.020 25815989; PubMed Central PMCID: PMC4547605.

4. Nakagawa S, Lagisz M, Hector KL, Spencer HG. Comparative and meta-analytic insights into life extension via dietary restriction. Aging Cell. 2012;11(3):401–9. doi: 10.1111/j.1474-9726.2012.00798.x 22268691.

5. Harper JM, Leathers CW, Austad SN. Does caloric restriction extend life in wild mice? Aging Cell. 2006;5(6):441–9. doi: 10.1111/j.1474-9726.2006.00236.x 17054664; PubMed Central PMCID: PMC2923404.

6. Liao CY, Rikke BA, Johnson TE, Diaz V, Nelson JF. Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging Cell. 2010;9(1):92–5. doi: 10.1111/j.1474-9726.2009.00533.x 19878144; PubMed Central PMCID: PMC3476836.

7. Schleit J, Johnson SC, Bennett CF, Simko M, Trongtham N, Castanza A, et al. Molecular mechanisms underlying genotype-dependent responses to dietary restriction. Aging Cell. 2013;12(6):1050–61. doi: 10.1111/acel.12130 23837470; PubMed Central PMCID: PMC3838465.

8. Dick KB, Ross CR, Yampolsky LY. Genetic variation of dietary restriction and the effects of nutrient-free water and amino acid supplements on lifespan and fecundity of Drosophila. Genet Res (Camb). 2011;93(4):265–73. Epub 2011/07/18. doi: 10.1017/S001667231100019X 21767463.

9. Stanley PD, Ng'oma E, O'Day S, King EG. Genetic Dissection of Nutrition-Induced Plasticity in Insulin/Insulin-Like Growth Factor Signaling and Median Life Span in a. Genetics. 2017;206(2):587–602. doi: 10.1534/genetics.116.197780 28592498; PubMed Central PMCID: PMC5499174.

10. Wilson KA, Beck JN, Nelson CS, Hilsabeck TA, Promislow D, Brem RB, Kapahi P. GWAS for lifespan and decline in climbing ability in flies upon dietary restriction reveal decima as a mediator of insulin-like peptide production. Curr Biol. 2020; in press.

11. Laye MJ, Tran V, Jones DP, Kapahi P, Promislow DE. The effects of age and dietary restriction on the tissue-specific metabolome of Drosophila. Aging Cell. 2015;14(5):797–808. doi: 10.1111/acel.12358 26085309; PubMed Central PMCID: PMC4568967.

12. Davies SK, Bundy JG, Leroi AM. Metabolic Youth in Middle Age: Predicting Aging in Caenorhabditis elegans Using Metabolomics. Journal of Proteome Research. 2015;14(11):4603–9. doi: 10.1021/acs.jproteome.5b00442 WOS:000364435100015. 26381038

13. Tomas-Loba A, de Jesus BB, Mato JM, Blasco MA. A metabolic signature predicts biological age in mice. Aging Cell. 2013;12(1):93–101. doi: 10.1111/acel.12025 WOS:000313745100012. 23107558

14. Lopez-Otin C, Galluzzi L, Freije JM, Madeo F, Kroemer G. Metabolic Control of Longevity. Cell. 2016;166(4):802–21. doi: 10.1016/j.cell.2016.07.031 27518560.

15. Ables GP, Brown-Borg HM, Buffenstein R, Church CD, Elshorbagy AK, Gladyshev VN, et al. The first international mini-symposium on methionine restriction and lifespan. Front Genet. 2014;5:122. doi: 10.3389/fgene.2014.00122 24847356; PubMed Central PMCID: PMC4023024.

16. Zimmerman JA, Malloy V, Krajcik R, Orentreich N. Nutritional control of aging. Experimental Gerontology. 2003;38(1–2):47–52. doi: 10.1016/s0531-5565(02)00149-3 WOS:000181155100007. 12543260

17. Zwighaft Z, Aviram R, Shalev M, Rousso-Noori L, Kraut-Cohen J, Golik M, et al. Circadian Clock Control by Polyamine Levels through a Mechanism that Declines with Age. Cell Metab. 2015;22(5):874–85. doi: 10.1016/j.cmet.2015.09.011 26456331.

18. Chin RM, Fu X, Pai MY, Vergnes L, Hwang H, Deng G, et al. The metabolite alpha-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR. Nature. 2014;510(7505):397–401. doi: 10.1038/nature13264 24828042; PubMed Central PMCID: PMC4263271.

19. Mishur RJ, Khan M, Munkacsy E, Sharma L, Bokov A, Beam H, et al. Mitochondrial metabolites extend lifespan. Aging Cell. 2016;15(2):336–48. doi: 10.1111/acel.12439 26729005; PubMed Central PMCID: PMC4783347.

20. Hoffman JM, Soltow QA, Li S, Sidik A, Jones DP, Promislow DE. Effects of age, sex, and genotype on high-sensitivity metabolomic profiles in the fruit fly, Drosophila melanogaster. Aging Cell. 2014;13(4):596–604. doi: 10.1111/acel.12215 24636523; PubMed Central PMCID: PMC4116462.

21. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747–53. doi: 10.1038/nature08494 19812666; PubMed Central PMCID: PMC2831613.

22. Field KJ, Lake JA. Environmental metabolomics links genotype to phenotype and predicts genotype abundance in wild plant populations. Physiol Plant. 2011;142(4):352–60. doi: 10.1111/j.1399-3054.2011.01480.x 21496032.

23. Chan EK, Rowe HC, Hansen BG, Kliebenstein DJ. The complex genetic architecture of the metabolome. PLoS Genet. 2010;6(11):e1001198. Epub 2010/11/04. doi: 10.1371/journal.pgen.1001198 21079692; PubMed Central PMCID: PMC2973833.

24. Suhre K, Shin SY, Petersen AK, Mohney RP, Meredith D, Wägele B, et al. Human metabolic individuality in biomedical and pharmaceutical research. Nature. 2011;477(7362):54–60. Epub 2011/08/31. doi: 10.1038/nature10354 21886157; PubMed Central PMCID: PMC3832838.

25. Gieger C, Geistlinger L, Altmaier E, Hrabé de Angelis M, Kronenberg F, Meitinger T, et al. Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum. PLoS Genet. 2008;4(11):e1000282. Epub 2008/11/28. doi: 10.1371/journal.pgen.1000282 19043545; PubMed Central PMCID: PMC2581785.

26. Illig T, Gieger C, Zhai G, Römisch-Margl W, Wang-Sattler R, Prehn C, et al. A genome-wide perspective of genetic variation in human metabolism. Nat Genet. 2010;42(2):137–41. Epub 2009/12/27. doi: 10.1038/ng.507 20037589; PubMed Central PMCID: PMC3773904.

27. Mackay TF, Richards S, Stone EA, Barbadilla A, Ayroles JF, Zhu D, et al. The Drosophila melanogaster Genetic Reference Panel. Nature. 2012;482(7384):173–8. doi: 10.1038/nature10811 22318601; PubMed Central PMCID: PMC3683990.

28. Huang W, Massouras A, Inoue Y, Peiffer J, Ramia M, Tarone AM, et al. Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines. Genome Res. 2014;24(7):1193–208. doi: 10.1101/gr.171546.113 24714809; PubMed Central PMCID: PMC4079974.

29. Ivanov DK, Escott-Price V, Ziehm M, Magwire MM, Mackay TF, Partridge L, et al. Longevity GWAS Using the Drosophila Genetic Reference Panel. J Gerontol A Biol Sci Med Sci. 2015;70(12):1470–8. doi: 10.1093/gerona/glv047 25922346; PubMed Central PMCID: PMC4631106.

30. Weber AL, Khan GF, Magwire MM, Tabor CL, Mackay TF, Anholt RR. Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster. PLoS One. 2012;7(4):e34745. doi: 10.1371/journal.pone.0034745 22496853; PubMed Central PMCID: PMC3319608.

31. Dobson AJ, Chaston JM, Newell PD, Donahue L, Hermann SL, Sannino DR, et al. Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster. Nat Commun. 2015;6:6312. doi: 10.1038/ncomms7312 25692519; PubMed Central PMCID: PMC4333721.

32. Mackay TFC, Huang W. Charting the genotype-phenotype map: lessons from the Drosophila melanogaster Genetic Reference Panel. Wiley Interdisciplinary Reviews-Developmental Biology. 2018;7(1). doi: 10.1002/wdev.289 WOS:000419120900001. 28834395

33. Sang JH, King RC. Nutritional Requirements of Axenically Cultured Drosophila melanogaster Adults. Journal of Experimental Biology1961. p. 793–809.

34. Osterwalder T, Yoon KS, White BH, Keshishian H. A conditional tissue-specific transgene expression system using inducible GAL4. Proc Natl Acad Sci U S A. 2001;98(22):12596–601. doi: 10.1073/pnas.221303298 11675495; PubMed Central PMCID: PMC60099.

35. Stack JH, Herman PK, Schu PV, Emr SD. A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole. EMBO J. 1993;12(5):2195–204. 8387919; PubMed Central PMCID: PMC413440.

36. Sano H, Nakamura A, Texada MJ, Truman JW, Ishimoto H, Kamikouchi A, et al. The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster. PLoS Genet. 2015;11(5):e1005209. doi: 10.1371/journal.pgen.1005209 26020940; PubMed Central PMCID: PMC4447355.

37. Ren GR, Hauser F, Rewitz KF, Kondo S, Engelbrecht AF, Didriksen AK, et al. CCHamide-2 Is an Orexigenic Brain-Gut Peptide in Drosophila. PLoS One. 2015;10(7):e0133017. doi: 10.1371/journal.pone.0133017 26168160; PubMed Central PMCID: PMC4500396.

38. Stadtman TC. Selenocysteine. Annu Rev Biochem. 1996;65:83–100. doi: 10.1146/annurev.bi.65.070196.000503 8811175.

39. Soultoukis GA, Partridge L. Dietary Protein, Metabolism, and Aging. Annual Review of Biochemistry, Vol 85. 2016;85:5–34. doi: 10.1146/annurev-biochem-060815-014422 WOS:000379324700003. 27145842

40. De Guzman JM, Ku G, Fahey R, Youm YH, Kass I, Ingram DK, et al. Chronic caloric restriction partially protects against age-related alteration in serum metabolome. Age (Dordr). 2013;35(4):1091–104. Epub 2012/06/04. doi: 10.1007/s11357-012-9430-x 22661299; PubMed Central PMCID: PMC3705111.

41. Pontoizeau C, Mouchiroud L, Molin L, Mergoud-Dit-Lamarche A, Dallière N, Toulhoat P, et al. Metabolomics analysis uncovers that dietary restriction buffers metabolic changes associated with aging in Caenorhabditis elegans. J Proteome Res. 2014;13(6):2910–9. Epub 2014/05/22. doi: 10.1021/pr5000686 24819046; PubMed Central PMCID: PMC4059273.

42. Mouchiroud L, Molin L, Kasturi P, Triba MN, Dumas ME, Wilson MC, et al. Pyruvate imbalance mediates metabolic reprogramming and mimics lifespan extension by dietary restriction in Caenorhabditis elegans. Aging Cell. 2011;10(1):39–54. Epub 2010/11/15. doi: 10.1111/j.1474-9726.2010.00640.x 21040400.

43. Avanesov AS, Ma S, Pierce KA, Yim SH, Lee BC, Clish CB, et al. Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation. Elife. 2014;3:e02077. Epub 2014/04/29. doi: 10.7554/eLife.02077 24843015; PubMed Central PMCID: PMC4003482.

44. Jové M, Naudí A, Ramírez-Núñez O, Portero-Otín M, Selman C, Withers DJ, et al. Caloric restriction reveals a metabolomic and lipidomic signature in liver of male mice. Aging Cell. 2014;13(5):828–37. Epub 2014/07/23. doi: 10.1111/acel.12241 25052291; PubMed Central PMCID: PMC4331741.

45. Rezzi S, Martin FP, Shanmuganayagam D, Colman RJ, Nicholson JK, Weindruch R. Metabolic shifts due to long-term caloric restriction revealed in nonhuman primates. Exp Gerontol. 2009;44(5):356–62. Epub 2009/03/03. doi: 10.1016/j.exger.2009.02.008 19264119; PubMed Central PMCID: PMC2822382.

46. Jablonski KL, Klawitter J, Chonchol M, Bassett CJ, Racine ML, Seals DR. Effect of dietary sodium restriction on human urinary metabolomic profiles. Clin J Am Soc Nephrol. 2015;10(7):1227–34. Epub 2015/04/21. doi: 10.2215/CJN.11531114 25901092; PubMed Central PMCID: PMC4491302.

47. Collet TH, Sonoyama T, Henning E, Keogh JM, Ingram B, Kelway S, et al. A Metabolomic Signature of Acute Caloric Restriction. J Clin Endocrinol Metab. 2017;102(12):4486–95. doi: 10.1210/jc.2017-01020 29029202; PubMed Central PMCID: PMC5718701.

48. Liao CY, Rikke BA, Johnson TE, Gelfond JA, Diaz V, Nelson JF. Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell. 2011;10(4):629–39. doi: 10.1111/j.1474-9726.2011.00702.x 21388497; PubMed Central PMCID: PMC3685291.

49. Cheng LY, Bailey AP, Leevers SJ, Ragan TJ, Driscoll PC, Gould AP. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell. 2011;146(3):435–47. doi: 10.1016/j.cell.2011.06.040 21816278.

50. Grandison RC, Piper MD, Partridge L. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature. 2009;462(7276):1061–4. doi: 10.1038/nature08619 19956092; PubMed Central PMCID: PMC2798000.

51. Lorenz DR, Cantor CR, Collins JJ. A network biology approach to aging in yeast. Proc Natl Acad Sci U S A. 2009;106(4):1145–50. Epub 2009/01/21. doi: 10.1073/pnas.0812551106 19164565; PubMed Central PMCID: PMC2629491.

52. Wuttke D, Connor R, Vora C, Craig T, Li Y, Wood S, et al. Dissecting the gene network of dietary restriction to identify evolutionarily conserved pathways and new functional genes. PLoS Genet. 2012;8(8):e1002834. Epub 2012/08/09. doi: 10.1371/journal.pgen.1002834 22912585; PubMed Central PMCID: PMC3415404.

53. Ghosh S, Wanders D, Stone KP, Van NT, Cortez CC, Gettys TW. A systems biology analysis of the unique and overlapping transcriptional responses to caloric restriction and dietary methionine restriction in rats. FASEB J. 2014;28(6):2577–90. Epub 2014/02/26. doi: 10.1096/fj.14-249458 24571921; PubMed Central PMCID: PMC4021438.

54. Hou L, Wang D, Chen D, Liu Y, Zhang Y, Cheng H, et al. A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction. Cell Metab. 2016;23(3):529–40. doi: 10.1016/j.cmet.2016.02.002 26959186; PubMed Central PMCID: PMC5110149.

55. De Luca M, Roshina NV, Geiger-Thornsberry GL, Lyman RF, Pasyukova EG, Mackay TF. Dopa decarboxylase (Ddc) affects variation in Drosophila longevity. Nat Genet. 2003;34(4):429–33. doi: 10.1038/ng1218 12881721.

56. Bjordal M, Arquier N, Kniazeff J, Pin JP, Leopold P. Sensing of amino acids in a dopaminergic circuitry promotes rejection of an incomplete diet in Drosophila. Cell. 2014;156(3):510–21. doi: 10.1016/j.cell.2013.12.024 24485457.

57. Linford NJ, Ro J, Chung BY, Pletcher SD. Gustatory and metabolic perception of nutrient stress in Drosophila. Proc Natl Acad Sci U S A. 2015;112(8):2587–92. doi: 10.1073/pnas.1401501112 25675472; PubMed Central PMCID: PMC4345594.

58. Ro J, Pak G, Malec PA, Lyu Y, Allison DB, Kennedy RT, et al. Serotonin signaling mediates protein valuation and aging. Elife. 2016;5. doi: 10.7554/eLife.16843 27572262; PubMed Central PMCID: PMC5005037.

59. Dus M, Lai JS, Gunapala KM, Min S, Tayler TD, Hergarden AC, et al. Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila. Neuron. 2015;87(1):139–51. doi: 10.1016/j.neuron.2015.05.032 26074004; PubMed Central PMCID: PMC4697866.

60. Pool AH, Kvello P, Mann K, Cheung SK, Gordon MD, Wang L, et al. Four GABAergic interneurons impose feeding restraint in Drosophila. Neuron. 2014;83(1):164–77. doi: 10.1016/j.neuron.2014.05.006 24991960; PubMed Central PMCID: PMC4092013.

61. Caggese C, Barsanti P, Viggiano L, Bozzetti MP, Caizzi R. Genetic, Molecular and Developmental Analysis of the Glutamine-Synthetase Isozymes of Drosophila melanogaster. Genetica. 1994;94(2–3):275–81. doi: 10.1007/BF01443441 WOS:A1994QH20800020. 7896146

62. Jayakumar S, Richhariya S, Reddy OV, Texada MJ, Hasan G. Drosophila larval to pupal switch under nutrient stress requires IP3R/Ca(2+) signalling in glutamatergic interneurons. Elife. 2016;5. doi: 10.7554/eLife.17495 27494275; PubMed Central PMCID: PMC4993588.

63. Post S, Karashchuk G, Wade JD, Sajid W, De Meyts P, Tatar M. Insulin-Like Peptides DILP2 and DILP5 Differentially Stimulate Cell Signaling and Glycogen Phosphorylase to Regulate Longevity. Front Endocrinol (Lausanne). 2018;9:245. Epub 2018/05/28. doi: 10.3389/fendo.2018.00245 29892262; PubMed Central PMCID: PMC5985746.

64. Hu Y, Flockhart I, Vinayagam A, Bergwitz C, Berger B, Perrimon N, et al. An integrative approach to ortholog prediction for disease-focused and other functional studies. BMC Bioinformatics. 2011;12:357. Epub 2011/08/31. doi: 10.1186/1471-2105-12-357 21880147; PubMed Central PMCID: PMC3179972.

65. Ramos-Alvarez I, Martin-Duce A, Moreno-Villegas Z, Sanz R, Aparicio C, Portal-Nunez S, et al. Bombesin receptor subtype-3 (BRS-3), a novel candidate as therapeutic molecular target in obesity and diabetes. Molecular and Cellular Endocrinology. 2013;367(1–2):109–15. doi: 10.1016/j.mce.2012.12.025 WOS:000315611600012. 23291341

66. Durham MF, Magwire MM, Stone EA, Leips J. Genome-wide analysis in Drosophila reveals age-specific effects of SNPs on fitness traits. Nat Commun. 2014;5:4338. Epub 2014/07/08. doi: 10.1038/ncomms5338 25000897.

67. Harvanek ZM, Lyu Y, Gendron CM, Johnson JC, Kondo S, Promislow DEL, et al. Perceptive costs of reproduction drive ageing and physiology in male Drosophila. Nat Ecol Evol. 2017;1(6):152. doi: 10.1038/s41559-017-0152 28812624; PubMed Central PMCID: PMC5657004.

68. Katewa SD, Akagi K, Bose N, Rakshit K, Camarella T, Zheng X, et al. Peripheral Circadian Clocks Mediate Dietary Restriction-Dependent Changes in Lifespan and Fat Metabolism in Drosophila. Cell Metab. 2016;23(1):143–54. doi: 10.1016/j.cmet.2015.10.014 26626459; PubMed Central PMCID: PMC4715572.

69. Nelson CS, Beck JN, Wilson KA, Pilcher ER, Kapahi P, Brem RB. Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila. BMC Genomics. 2016;17(1):867. doi: 10.1186/s12864-016-3137-9 27809764; PubMed Central PMCID: PMC5095962.

70. Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, et al. 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell. 2009;139(1):149–60. doi: 10.1016/j.cell.2009.07.034 19804760; PubMed Central PMCID: PMC2759400.

71. Chapman T, Partridge L. Female fitness in Drosophila melanogaster: An interaction between the effect of nutrition and of encounter rate with males. Proceedings of the Royal Society B-Biological Sciences. 1996;263(1371):755–9. doi: 10.1098/rspb.1996.0113 WOS:A1996UW13400013. 8763795

72. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Current Biology. 2004;14(10):885–90. doi: 10.1016/j.cub.2004.03.059 WOS:000221681600025. 15186745

73. Partridge L, Piper MD, Mair W. Dietary restriction in Drosophila. Mech Ageing Dev. 2005;126(9):938–50. doi: 10.1016/j.mad.2005.03.023 15935441.

74. Lang S, Hilsabeck TA, Wilson KA, Sharma A, Bose N, Brackman DJ, et al. A conserved role of the insulin-like signaling pathway in diet-dependent uric acid pathologies in Drosophila melanogaster. PLoS Genet. 2019;15(8):e1008318. Epub 2019/08/15. doi: 10.1371/journal.pgen.1008318 31415568; PubMed Central PMCID: PMC6695094.

75. Sperber H, Mathieu J, Wang Y, Ferreccio A, Hesson J, Xu Z, et al. The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition. Nat Cell Biol. 2015;17(12):1523–35. doi: 10.1038/ncb3264 26571212; PubMed Central PMCID: PMC4662931.

76. Du J, Rountree A, Cleghorn WM, Contreras L, Lindsay KJ, Sadilek M, et al. Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina. J Biol Chem. 2016;291(9):4698–710. doi: 10.1074/jbc.M115.698985 26677218; PubMed Central PMCID: PMC4813492.

77. Chiao YA, Kolwicz SC, Basisty N, Gagnidze A, Zhang J, Gu H, et al. Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts. Aging (Albany NY). 2016;8(2):314–27. doi: 10.18632/aging.100881 26872208; PubMed Central PMCID: PMC4789585.

78. R Core Team. R: A language and environment for statistical computing. In: Computing RFfS, editor. Vienna, Austria2014.

79. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate—a Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B-Methodological. 1995;57(1):289–300. WOS:A1995QE45300017.

80. Hastie T, Tibshirani R, Narasimhan B, Chu G. impute: impute: Imputation for microarray data.: R package version 1.56.0.; 2018.

81. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75. doi: 10.1086/519795 17701901; PubMed Central PMCID: PMC1950838.

82. Gao J, Tarcea VG, Karnovsky A, Mirel BR, Weymouth TE, Beecher CW, et al. Metscape: a Cytoscape plug-in for visualizing and interpreting metabolomic data in the context of human metabolic networks. Bioinformatics. 2010;26(7):971–3. doi: 10.1093/bioinformatics/btq048 20139469; PubMed Central PMCID: PMC2844990.


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 7

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy Doporučená témata Časopisy
Přihlášení
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

VIRTUÁLNÍ ČEKÁRNA ČR Jste praktický lékař nebo pediatr? Zapojte se! Jste praktik nebo pediatr? Zapojte se!

×