, Volume 19, Issue 1, pp 33–45 | Cite as

Epigenetic factors Polycomb (Pc) and Suppressor of zeste (Su(z)2) negatively regulate longevity in Drosophila melanogaster

  • Vasanthi Dasari
  • Surabhi Srivastava
  • Shagufta Khan
  • Rakesh K. Mishra
Research Article


The process of aging is a hallmark of the natural life span of all organisms and individuals within a population show variability in the measures of age related performance. Longevity and the rate of aging are influenced by several factors such as genetics, nutrition, stress, and environment. Many studies have focused on the genes that impact aging and there is increasing evidence that epigenetic factors regulate these genes to control life span. Polycomb (PcG) and trithorax (trxG) protein complexes maintain the expression profiles of developmentally important genes and regulate many cellular processes. Here, we report that mutations of PcG and trxG members affect the process of aging in Drosophila melanogaster, with perturbations mostly associated with retardation in aging. We find that mutations in polycomb repressive complex (PRC1) components Pc and Su(z)2 increase fly survival. Using an inducible UAS-GAL4 system, we show that this effect is tissue-specific; knockdown in fat body, but not in muscle or brain tissues, enhances life span. We hypothesize that these two proteins influence life span via pathways independent of their PRC1 functions, with distinct effects on response to oxidative stress. Our observations highlight the role of global epigenetic regulators in determining life span.


Polycomb Longevity Fat body PRC1 Drosophila melanogaster Oxidative stress 



We acknowledge F Karch, Yacine Graba, Mel Feany and BDSC for fly strains and Prashanth Budnar for suggestions.


This study was funded by SERB, a statutory body under the Government of India’s Department of Science & Technology. SK is supported by DST-INSPIRE fellowship. RKM lab is supported by Council of Scientific and Industrial Research (BSC0208) and Department of Biotechnology (Government of India).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10522_2017_9737_MOESM1_ESM.pptx (3.3 mb)
Supplementary material 1 (PPTX 3383 kb)


  1. Ali JY, Bender W (2004) Cross-regulation among the polycomb group genes in Drosophila melanogaster. Mol Cell Biol 24:7737–7747. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Altintas O, Park S, Lee SJ (2016) The role of insulin/IGF-1 signaling in the longevity of model invertebrates, C. elegans and D. melanogaster. BMB Rep 49:81–92CrossRefPubMedPubMedCentralGoogle Scholar
  3. Arking R, Buck S, Berrios A, Dwyer S, Baker GT 3rd (1991) Elevated paraquat resistance can be used as a bioassay for longevity in a genetically based long-lived strain of Drosophila. Dev Genet 12:362–370. CrossRefPubMedGoogle Scholar
  4. Armstrong VL, Rakoczy S, Rojanathammanee L, Brown-Borg HM (2014) Expression of DNA methyltransferases is influenced by growth hormone in the long-living Ames dwarf mouse in vivo and in vitro. J Gerontol Ser A 69:923–933. CrossRefGoogle Scholar
  5. Astrom SU, Cline TW, Rine J (2003) The Drosophila melanogaster sir2+ gene is nonessential and has only minor effects on position-effect variegation. Genetics 163:931–937PubMedPubMedCentralGoogle Scholar
  6. Banerjee KK, Ayyub C, Ali SZ, Mandot V, Prasad NG, Kolthur-Seetharam U (2012a) dSir2 in the adult fat body, but not in muscles, regulates life span in a diet-dependent manner. Cell Rep 2:1485–1491.
  7. Banerjee KK, Ayyub C, Sengupta S, Kolthur-Seetharam U (2012b) dSir2 deficiency in the fatbody, but not muscles, affects systemic insulin signaling, fat mobilization and starvation survival in flies. Aging (Albany NY) 4:206–223.
  8. Bauer JH, Morris SN, Chang C, Flatt T, Wood JG, Helfand SL (2009) dSir2 and Dmp53 interact to mediate aspects of CR-dependent lifespan extension in D. melanogaster. Aging (Albany NY) 1:38–48.
  9. Colodner KJ, Feany MB (2010) Glial fibrillary tangles and JAK/STAT-mediated glial and neuronal cell death in a Drosophila model of glial tauopathy. J Neurosci 30:16102–16113. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dang W et al (2014) Inactivation of yeast Isw2 chromatin remodeling enzyme mimics longevity effect of calorie restriction via induction of genotoxic stress response. Cell Metab 19:952–966. CrossRefPubMedPubMedCentralGoogle Scholar
  11. Feinberg AP (2008) Epigenetics at the epicenter of modern medicine. JAMA 299:1345–1350. CrossRefPubMedGoogle Scholar
  12. Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194:7–15. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247. CrossRefPubMedGoogle Scholar
  14. Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418. CrossRefPubMedGoogle Scholar
  15. Francis NJ, Kingston RE, Woodcock CL (2004) Chromatin compaction by a polycomb group protein complex. Science 306:1574–1577. CrossRefPubMedGoogle Scholar
  16. Frankel S, Ziafazeli T, Rogina B (2011) dSir2 and longevity in Drosophila. Exp Gerontol 46:391–396. CrossRefPubMedGoogle Scholar
  17. Fujii M, Tanaka N, Miki K, Hossain MN, Endoh M, Ayusawa D (2005) Uncoupling of longevity and paraquat resistance in mutants of the nematode Caenorhabditis elegans. Biosci Biotechnol Biochem 69:2015–2018. CrossRefPubMedGoogle Scholar
  18. Girardot F, Lasbleiz C, Monnier V, Tricoire H (2006) Specific age-related signatures in Drosophila body parts transcriptome. BMC Genomics 7:69. CrossRefPubMedPubMedCentralGoogle Scholar
  19. Gorfinkiel N, Fanti L, Melgar T, Garcia E, Pimpinelli S, Guerrero I, Vidal M (2004) The Drosophila Polycomb group gene sex combs extra encodes the ortholog of mammalian Ring1 proteins. Mech Dev 121:449–462. CrossRefPubMedGoogle Scholar
  20. Greer EL et al. (2010) Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature 466:383–387.
  21. Haigis MC, Yankner BA (2010) The aging stress response. Mol Cell 40:333–344. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Houtkooper RH, Pirinen E, Auwerx J (2012) Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13:225–238. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hunt LC, Demontis F (2013) Whole-mount immunostaining of Drosophila skeletal muscle. Nat Protoc 8:2496–2501. CrossRefPubMedGoogle Scholar
  24. Hwangbo DS, Gershman B, Tu MP, Palmer M, Tatar M (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429:562–566. CrossRefPubMedGoogle Scholar
  25. Janody F, Martirosyan Z, Benlali A, Treisman JE (2003) Two subunits of the Drosophila mediator complex act together to control cell affinity. Development 130:3691–3701CrossRefPubMedGoogle Scholar
  26. Jin C et al (2011) Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metab 14:161–172. CrossRefPubMedGoogle Scholar
  27. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493:338–345.
  28. Katewa SD, Kapahi P (2010) Dietary restriction and aging, 2009. Aging Cell 9:105–112. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Killip LE, Grewal SS (2012) DREF is required for cell and organismal growth in Drosophila and functions downstream of the nutrition/TOR pathway. Dev Biol 371:191–202. CrossRefPubMedGoogle Scholar
  30. Kolodziejczyk A, Sun X, Meinertzhagen IA, Nassel DR (2008) Glutamate, GABA and acetylcholine signaling components in the lamina of the Drosophila visual systemGABA and acetylcholine signaling components in the lamina of the Drosophila visual system. PLoS One 3:e2110. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kroll JR, Tanouye MA (2013) Rescue of easily shocked mutant seizure sensitivity in Drosophila adults. J Comp Neurol 521:3500–3507. CrossRefPubMedPubMedCentralGoogle Scholar
  32. Landis GN et al (2004) Similar gene expression patterns characterize aging and oxidative stress in Drosophila melanogaster. Proc Natl Acad Sci USA 101:7663–7668. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Lanzuolo C, Orlando V (2012) Memories from the polycomb group proteins. Annu Rev Genet 46:561–589. CrossRefPubMedGoogle Scholar
  34. Lee BC et al (2014) Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status. Nat Commun 5:3592. PubMedPubMedCentralGoogle Scholar
  35. Li L, Greer C, Eisenman RN, Secombe J (2010) Essential functions of the histone demethylase lid. PLoS Genet 6:e1001221. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Mockett RJ, Orr WC, Rahmandar JJ, Sohal BH, Sohal RS (2001) Antioxidant status and stress resistance in long- and short-lived lines of Drosophila melanogaster. Exp Gerontol 36:441–463CrossRefPubMedGoogle Scholar
  38. Morillo Prado JR, Chen X, Fuller MT (2012) Polycomb group genes Psc and Su(z)2 maintain somatic stem cell identity and activity in Drosophila. PLoS ONE 7:e52892. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Munoz-Najar U, Sedivy JM (2011) Epigenetic control of aging. Antioxid Redox Signal 14:241–259. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Pal S, Tyler JK (2016) Epigenetics and aging. Sci Adv 2:e1600584. CrossRefPubMedPubMedCentralGoogle Scholar
  41. Partridge L, Alic N, Bjedov I, Piper MD (2011) Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network. Exp Gerontol 46:376–381. CrossRefPubMedPubMedCentralGoogle Scholar
  42. Pasini D, Di Croce L (2016) Emerging roles for Polycomb proteins in cancer. Curr Opin Genet Dev 36:50–58. CrossRefPubMedGoogle Scholar
  43. Peleg S, Feller C, Ladurner AG, Imhof A (2016) The metabolic impact on histone acetylation and transcription in ageing. Trends Biochem Sci 41:700–711. CrossRefPubMedGoogle Scholar
  44. 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 12:712–723CrossRefPubMedGoogle Scholar
  45. Poynter ST, Kadoch C (2016) Polycomb and trithorax opposition in development and disease. Wiley Interdiscip Rev 5:659–688. CrossRefGoogle Scholar
  46. Salmon AB, Richardson A, Perez VI (2010) Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging? Free Radic Biol Med 48:642–655. CrossRefPubMedGoogle Scholar
  47. Schwartz YB, Pirrotta V (2013) A new world of Polycombs: unexpected partnerships and emerging functions. Nat Rev Genet 14:853–864. CrossRefPubMedGoogle Scholar
  48. Schwartz YB, Kahn TG, Nix DA, Li XY, Bourgon R, Biggin M, Pirrotta V (2006) Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet 38:700–705. CrossRefPubMedGoogle Scholar
  49. Shaposhnikov M, Proshkina E, Shilova L, Zhavoronkov A, Moskalev A (2015) Lifespan and stress resistance in Drosophila with overexpressed DNA repair genes. Sci Rep 5:15299. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Siebold AP, Banerjee R, Tie F, Kiss DL, Moskowitz J, Harte PJ (2010) Polycomb repressive complex 2 and trithorax modulate Drosophila longevity and stress resistance. Proc Natl Acad Sci USA 107:169–174. CrossRefPubMedGoogle Scholar
  51. Sparmann A, van Lohuizen M (2006) Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 6:846–856. CrossRefPubMedGoogle Scholar
  52. Steinkraus KA et al (2008) Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1-dependent mechanism in Caenorhabditis elegans. Aging Cell 7:394–404. CrossRefPubMedPubMedCentralGoogle Scholar
  53. Travers LM, Garcia-Gonzalez F, Simmons LW (2015) Live fast die young life history in females: evolutionary trade-off between early life mating and lifespan in female Drosophila melanogaster. Sci Rep 5:15469. CrossRefPubMedPubMedCentralGoogle Scholar
  54. Van Raamsdonk JM, Hekimi S (2012) Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci USA 109:5785–5790. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Vasanthi D, Nagabhushan A, Matharu NK, Mishra RK (2013) A functionally conserved Polycomb response element from mouse HoxD complex responds to heterochromatin factors. Sci Rep 3:3011. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Vermeulen CJ, Van De Zande L, Bijlsma R (2005) Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster. Biogerontology 6:387–395. CrossRefPubMedGoogle Scholar
  57. Walter MF, Biessmann MR, Benitez C, Torok T, Mason JM, Biessmann H (2007) Effects of telomere length in Drosophila melanogaster on life span, fecundity, and fertility. Chromosoma 116:41–51. CrossRefPubMedGoogle Scholar
  58. Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, Zhang Y (2004a) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431:873–878.
  59. Wang HD, Kazemi-Esfarjani P, Benzer S (2004b) Multiple-stress analysis for isolation of Drosophila longevity genes. Proc Natl Acad Sci USA 101:12610–12615. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Wang L, Karpac J, Jasper H (2014) Promoting longevity by maintaining metabolic and proliferative homeostasis. J Exp Biol 217:109–118. CrossRefPubMedPubMedCentralGoogle Scholar
  61. Yang JS et al (2011) OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS ONE 6:e23525. CrossRefPubMedPubMedCentralGoogle Scholar
  62. Zahn JM, Kim SK (2007) Systems biology of aging in four species. Curr Opin Biotechnol 18:355–359. CrossRefPubMedPubMedCentralGoogle Scholar
  63. Zane L, Sharma V, Misteli T (2014) Common features of chromatin in aging and cancer: cause or coincidence? Trends Cell Biol 24:686–694. CrossRefPubMedPubMedCentralGoogle Scholar
  64. Zeng X, Lin X, Hou SX (2013) The Osa-containing SWI/SNF chromatin-remodeling complex regulates stem cell commitment in the adult Drosophila intestine. Development 140:3532–3540. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2017

Authors and Affiliations

  1. 1.CSIR - Centre for Cellular and Molecular BiologyHyderabadIndia

Personalised recommendations