, Volume 12, Issue 2, pp 93–107 | Cite as

Genome-wide analysis of low-dose irradiated male Drosophila melanogaster with extended longevity

  • Ki Moon Seong
  • Cha Soon Kim
  • Sun-Won Seo
  • Ha Yeon Jeon
  • Byung-Sub Lee
  • Seon Young Nam
  • Kwang Hee Yang
  • Ji-Young Kim
  • Chong Soon Kim
  • Kyung-Jin Min
  • Young-Woo Jin
Research Article


Ionizing radiation generates oxidative stress, which is thought to be a major cause of aging. Although living organisms are constantly exposed to low levels of radiation, most studies examining the effect of radiation have focused on accelerated aging and diminished life span that result from high-dose radiation. On the other hand, several studies have suggested that low-dose radiation enhances the longevity of Drosophila melanogaster. Therefore, investigation of the biological effects of low-dose radiation could contribute to a more comprehensive understanding of the aging process. In this study, microarray and quantitative real time-PCR were used to measure genome-wide changes in transcript levels in low-dose irradiated fruit flies that showed enhanced longevity. In response to radiation, approximately 13% of the genome exhibited changes in gene expression, and a number of aging-related genes were significantly regulated. These data were compared with quantitative trait loci affecting life-span to identify candidate genes involved in enhanced longevity induced by low-dose radiation. This genome-wide survey revealed novel information about changes in transcript levels in low-dose irradiated flies and identified 39 new candidate genes for molecular markers of extended longevity induced by ionizing radiation. In addition, this study also suggests a mechanism by which low-dose radiation extends longevity.


Life span Low-dose radiation Microarray gene expression Drosophila aging 



This work was supported by grants from the Korea Hydro and Nuclear Power Co., Ltd., A08NJ23 and the Ministry of Education, Science and Technology (MEST) and National Research Foundation of Korea (NRF) through Nuclear R&D Program, 2009 (No. 39584).

Supplementary material

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  1. Arbeitman MN, Furlong EE, Imam F, Johnson E, Null BH, Baker BS, Krasnow MA, Scott MP, Davis RW, White KP (2002) Gene expression during the life cycle of Drosophila melanogaster. Science 297:2270–2275PubMedCrossRefGoogle Scholar
  2. Bordone L, Guarente L (2005) Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 6:298–305PubMedCrossRefGoogle Scholar
  3. Carrano AC, Liu Z, Dillin A, Hunter T (2009) A conserved ubiquitination pathway determines longevity in response to diet restriction. Nature 460:396–399PubMedGoogle Scholar
  4. Cha HJ, Seong KM, Bae S, Jung JH, Kim CS, Yang KH, Jin YW, An S (2009) Identification of specific microRNAs responding to low and high dose gamma-irradiation in the human lymphoblast line IM9. Oncol Rep 22:863–868PubMedGoogle Scholar
  5. 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:R262PubMedCrossRefGoogle Scholar
  6. De Gregorio E, Spellman PT, Rubin GM, Lemaitre B (2001) Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays. Proc Natl Acad Sci USA 98:12590–12595PubMedCrossRefGoogle Scholar
  7. Garinis GA, van der Horst GT, Vijg J, Hoeijmakers JH (2008) DNA damage and ageing: new-age ideas for an age-old problem. Nat Cell Biol 10:1241–1247PubMedCrossRefGoogle Scholar
  8. Gems D, Sutton AJ, Sundermeyer ML, Albert PS, King KV, Edgley ML, Larsen PL, Riddle DL (1998) Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150:129–155PubMedGoogle Scholar
  9. Girardot F, Monnier V, Tricoire H (2004) Genome wide analysis of common and specific stress responses in adult Drosophila melanogaster. BMC Genomics 5:74PubMedCrossRefGoogle Scholar
  10. Goberdhan DC, Wilson C (2003) The functions of insulin signaling: size isn’t everything, even in Drosophila. Differentiation 71:375–397PubMedCrossRefGoogle Scholar
  11. Gottlieb RA (2003) Cytochrome P450: major player in reperfusion injury. Arch Biochem Biophys 420:262–267PubMedCrossRefGoogle Scholar
  12. Gruntenko NE, Chentsova NA, Andreenkova EV, Bownes M, Segal D, Adonyeva NV, Rauschenbach IY (2003) Stress response in a juvenile hormone-deficient Drosophila melanogaster mutant apterous56f. Insect Mol Biol 12:353–363PubMedCrossRefGoogle Scholar
  13. Ja WW, West AP Jr, Delker SL, Bjorkman PJ, Benzer S, Roberts RW (2007) Extension of Drosophila melanogaster life span with a GPCR peptide inhibitor. Nat Chem Biol 3:415–419PubMedCrossRefGoogle Scholar
  14. Kaeberlein M, Kennedy BK (2007) Protein translation, 2007. Aging Cell 6:731–734PubMedCrossRefGoogle Scholar
  15. Kawamura K, Shibata T, Saget O, Peel D, Bryant PJ (1999) A new family of growth factors produced by the fat body and active on Drosophila imaginal disc cells. Development 126:211–219PubMedGoogle Scholar
  16. Khazaeli AA, Van Voorhies W, Curtsinger JW (2005) The relationship between life span and adult body size is highly strain-specific in Drosophila melanogaster. Exp Gerontol 40:377–385PubMedCrossRefGoogle Scholar
  17. Kirkwood TB (2005) Understanding the odd science of aging. Cell 120:437–447PubMedCrossRefGoogle Scholar
  18. Lai CQ, Parnell LD, Lyman RF, Ordovas JM, Mackay TF (2007) Candidate genes affecting Drosophila life span identified by integrating microarray gene expression analysis and QTL mapping. Mech Ageing Dev 128:237–249PubMedCrossRefGoogle Scholar
  19. Lamb MJ, Smith JM (1969) Radiation-induced life-shortening in Drosophila. Radiat Res 40:450–464PubMedCrossRefGoogle Scholar
  20. Lee JW, Seong KM, Kim CS, Nam SY, Yang KH, Jin Y (2008) Low-dose gamma-irradiation effect on early stage development and lifespan in various strains of Drosophila melanogaster. Korean J Occup Environ Med 20:225–232Google Scholar
  21. Leips J, Mackay TF (2000) Quantitative trait loci for life span in Drosophila melanogaster: interactions with genetic background and larval density. Genetics 155:1773–1788PubMedGoogle Scholar
  22. Leips J, Mackay TF (2002) The complex genetic architecture of Drosophila life span. Exp Aging Res 28:361–390PubMedCrossRefGoogle Scholar
  23. Leroi AM (2001) Molecular signals versus the Loi de Balancement. Trends Ecol Evol 16:24–29PubMedCrossRefGoogle Scholar
  24. Marples B, Collis SJ (2008) Low-dose hyper-radiosensitivity: past, present, and future. Int J Radiat Oncol Biol Phys 70:1310–1318PubMedCrossRefGoogle Scholar
  25. Marshall RA, Aitken CE, Dorywalska M, Puglisi JD (2008) Translation at the single-molecule level. Annu Rev Biochem 77:177–203PubMedCrossRefGoogle Scholar
  26. Melvin RG, Van Voorhies WA, Ballard JW (2007) Working harder to stay alive: metabolic rate increases with age in Drosophila simulans but does not correlate with life span. J Insect Physiol 53:1300–1306PubMedCrossRefGoogle Scholar
  27. Moskalev A (2007) Radiation-induced life span alteration of Drosophila lines with genotype differences. Biogerontology 8:499–504PubMedCrossRefGoogle Scholar
  28. Moskalev A, Yazkiv A, Zainullin V (2006) Effect of low-dose irradiation on the lifespan in various strains of Drosophila melanogaster. Russ J Genet 42:628–635CrossRefGoogle Scholar
  29. Moskalev A, Shaposhnikov M, Turysheva E (2009) Life span alteration after irradiation in Drosophila melanogaster strains with mutations of Hsf and Hsps. Biogerontology 10:3–11PubMedCrossRefGoogle Scholar
  30. Neufeld JD, Mohn WW (2005) Fluorophore-labeled primers improve the sensitivity, versatility, and normalization of denaturing gradient gel electrophoresis. Appl Environ Microbiol 71:4893–4896PubMedCrossRefGoogle Scholar
  31. Nothel H (1983) Investigations on radiosensitive and radioresistant populations of Drosophila melanogaster. XVI. Adaptation to the mutagenic effects of X-rays in several experimental populations with irradiation histories. Mutat Res 111:325–340PubMedCrossRefGoogle Scholar
  32. Nothel H (1987) Adaptation of Drosophila melanogaster populations to high mutation pressure: evolutionary adjustment of mutation rates. Proc Natl Acad Sci USA 84:1045–1049PubMedCrossRefGoogle Scholar
  33. Nuzhdin SV, Pasyukova EG, Dilda CL, Zeng ZB, Mackay TF (1997) Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster. Proc Natl Acad Sci USA 94:9734–9739PubMedCrossRefGoogle Scholar
  34. O’Brien DM, Min KJ, Larsen T, Tatar M (2008) Use of stable isotopes to examine how dietary restriction extends Drosophila lifespan. Curr Biol 18:R155–R156PubMedCrossRefGoogle Scholar
  35. O’Driscoll M, Jeggo PA (2006) The role of double-strand break repair—insights from human genetics. Nat Rev Genet 7:45–54PubMedCrossRefGoogle Scholar
  36. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:994–999PubMedCrossRefGoogle Scholar
  37. Ogura K, Magae J, Kawakami Y, Koana T (2009) Reduction in mutation frequency by very low-dose gamma irradiation of Drosophila melanogaster germ cells. Radiat Res 171:1–8PubMedCrossRefGoogle Scholar
  38. Paaby AB, Schmidt PS (2009) Dissecting the genetics of longevity in Drosophila melanogaster. Fly (Austin) 3:29–38Google Scholar
  39. Partridge L, Piper MD, Mair W (2005) Dietary restriction in Drosophila. Mech Ageing Dev 126:938–950PubMedCrossRefGoogle Scholar
  40. Pletcher SD, Houle D, Curtsinger JW (1999) The evolution of age-specific mortality rates in Drosophila melanogaster: genetic divergence among unselected lines. Genetics 153:813–823PubMedGoogle Scholar
  41. Pletcher SD, Macdonald SJ, Marguerie R, Certa U, Stearns SC, Goldstein DB, Partridge L (2002) Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster. Curr Biol 12:712–723PubMedCrossRefGoogle Scholar
  42. Pollycove M (2007) Radiobiological basis of low-dose irradiation in prevention and therapy of cancer. Dose Response 5:26–38CrossRefGoogle Scholar
  43. Sarantseva SV, Khromykh YM (2001) Effects of gamma-radiation in oogenesis of Drosophila mutants defective for repair and meiotic recombination. Russ J Genet 37:631–638CrossRefGoogle Scholar
  44. Sgrò MC, Partridge L (1999) A delayed wave of death from reproduction in Drosophila. Science 286:2521–2524Google Scholar
  45. Shmookler Reis RJ, Kang P, Ayyadevara S (2006) Quantitative trait loci define genes and pathways underlying genetic variation in longevity. Exp Gerontol 41:1046–1054PubMedCrossRefGoogle Scholar
  46. Tatar M (2005) Comment on “Long-lived Drosophila with overexpressed dFOXO in adult fat body”. Science 307:675 (author reply 675)Google Scholar
  47. Tissenbaum HA, Ruvkun G (1998) An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics 148:703–717PubMedGoogle Scholar
  48. Tu MP, Tatar M (2003) Juvenile diet restriction and the aging and reproduction of adult Drosophila melanogaster. Aging Cell 2:327–333PubMedCrossRefGoogle Scholar
  49. Tubiana M (2009) Prevention of cancer and the dose-effect relationship: the carcinogenic effects of ionizing radiations. Cancer Radiother 13:238–258PubMedGoogle Scholar
  50. Vermeulen CJ, Bijlsma R, Loeschcke V (2008) QTL mapping of inbreeding-related cold sensitivity and conditional lethality in Drosophila melanogaster. J Evol Biol 21:1236–1244PubMedCrossRefGoogle Scholar
  51. Vieira C, Pasyukova EG, Zeng ZB, Hackett JB, Lyman RF, Mackay TF (2000) Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster. Genetics 154:213–227PubMedGoogle Scholar
  52. Villeneuve JP, Pichette V (2004) Cytochrome P450 and liver diseases. Curr Drug Metab 5:273–282PubMedCrossRefGoogle Scholar
  53. Wang Y, Pot D, Kachman SD, Nuzhdin SV, Harshman LG (2006) A quantitative trait locus analysis of natural genetic variation for Drosophila melanogaster oxidative stress survival. J Hered 97:355–366PubMedCrossRefGoogle Scholar
  54. Warner JR, McIntosh KB (2009) How common are extraribosomal functions of ribosomal proteins? Mol Cell 34:3–11PubMedCrossRefGoogle Scholar
  55. Weizman N, Shiloh Y, Barzilai A (2003) Contribution of the Atm protein to maintaining cellular homeostasis evidenced by continuous activation of the AP-1 pathway in Atm-deficient brains. J Biol Chem 278:6741–6747PubMedCrossRefGoogle Scholar
  56. West AP Jr, Llamas LL, Snow PM, Benzer S, Bjorkman PJ (2001) Crystal structure of the ectodomain of Methuselah, a Drosophila G protein-coupled receptor associated with extended lifespan. Proc Natl Acad Sci USA 98:3744–3749PubMedCrossRefGoogle Scholar
  57. Zou S, Meadows S, Sharp L, Jan LY, Jan YN (2000) Genome-wide study of aging and oxidative stress response in Drosophila melanogaster. Proc Natl Acad Sci USA 97:13726–13731PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Ki Moon Seong
    • 1
  • Cha Soon Kim
    • 1
  • Sun-Won Seo
    • 1
  • Ha Yeon Jeon
    • 1
  • Byung-Sub Lee
    • 2
  • Seon Young Nam
    • 1
  • Kwang Hee Yang
    • 1
  • Ji-Young Kim
    • 1
  • Chong Soon Kim
    • 3
  • Kyung-Jin Min
    • 2
  • Young-Woo Jin
    • 1
  1. 1.Division of Radiation Effect Research, Radiation Health Research InstituteKorea Hydro & Nuclear Power Co., Ltd.SeoulKorea
  2. 2.Department of Biological SciencesInha UniversityIncheonKorea
  3. 3.Department of Nuclear Medicine, Haeundae Paik HospitalInje UniversityBusanKorea

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