Advertisement

AGE

, Volume 36, Issue 1, pp 213–221 | Cite as

Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels

  • Agavni Petrosyan
  • Óscar F. Gonçalves
  • I-Hui Hsieh
  • Kourosh Saberi
Article

Abstract

Methuselah (mth) is a chromosome 3 Drosophila mutant with an increased lifespan. A large number of studies have investigated the genetic, molecular, and biochemical mechanisms of the mth gene. Much less is known about the effects of mth on preservation of sensorimotor abilities throughout Drosophila’s lifespan, particularly in late life. The current study investigated functional senescence in mth and its parental-control line (w1118) in two experiments that measured age-dependent changes in flight functions and locomotor activity. In experiment 1, a total of 158 flies (81 mth and 77 controls) with an age range from 10 to 70 days were individually tethered under an infrared laser-sensor system that allowed monitoring of flight duration during phototaxic flight. We found that mth has a statistically significant advantage in maintaining continuous flight over control flies at age 10 days, but not during middle and late life. At age 70 days, the trend reversed and parental control flies had a small but significant advantage, suggesting an interaction between age and genotype in the ability to sustain flight. In experiment 2, a total of 173 different flies (97 mth and 76 controls) with an age range from 50 to 76 days were individually placed in a large well-lit arena (60 × 45 cm) and their locomotor activity quantified as the distance walked in a 1-min period. Results showed that mth flies had lower levels of locomotor activity relative to controls at ages 50 and 60 days. These levels converged for the two genotypes at the oldest ages tested. Findings show markedly different patterns of functional decline for the mth line relative to those previously reported for other life-extended genotypes, suggesting that different life-extending genes have dissimilar effects on preservation of sensory and motor abilities throughout an organism’s lifespan.

Keywords

Drosophila Longevity mth Methuselah Aging Sensorimotor Locomotor Behavior 

Notes

Acknowledgments

The mth and control flies were graciously provided by the laboratory of the late Prof. Seymour Benzer. We thank Rosana Magalhães, Eugénia Fernandes, and Jorge Alves for helpful discussions. This work was supported by funding from the University of California, Irvine, and from the University of Minho, Portugal.

References

  1. Baldal EA, Baktawar W, Brakefield PM, Zwaan BJ (2006) Methuselah life history in a variety of conditions, implications for the use of mutants in longevity research. Exp Gerontol 41:1126–1135PubMedCrossRefGoogle Scholar
  2. Barja G (2004) Free radicals and aging. Trends Neurosci 27:595–600PubMedCrossRefGoogle Scholar
  3. Bland ND, Robinson P, Thomas JE, Shirras AD, Turner AJ, Isaac RE (2009) Locomotor and geotactic behavior of Drosophila melanogaster over-expressing neprilysin. Peptides 30:571–574PubMedCrossRefGoogle Scholar
  4. Bokov A, Chaudhuri A, Richardson A (2004) The role of oxidative damage and stress in aging. Mech Aging Dev 125:811–826PubMedCrossRefGoogle Scholar
  5. Butler D (1999) Venter's Drosophila 'success' set to boost human genome efforts. Nature 401:729–730PubMedCrossRefGoogle Scholar
  6. Cvejic S, Zhu Z, Felice SJ, Berman Y, Huang XY (2004) The endogenous ligand Stunted of the GPCR Methuselah extends lifespan in Drosophila. Nat Cell Biol 6:540–546PubMedCrossRefGoogle Scholar
  7. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292:104–106PubMedCrossRefGoogle Scholar
  8. Clancy DJ, Gems D, Hafen E, Leevers SJ, Partridge L (2002) Dietary restriction in long-lived dwarf flies. Science 296:319PubMedCrossRefGoogle Scholar
  9. Cook-Wiens E, Grotewiel MS (2002) Dissociation between functional senescence and oxidative stress resistance in Drosophila. Exp Gerontol 37:1345–1355CrossRefGoogle Scholar
  10. Curtsinger JW, Fukui HH, Khazaeli AA, Kirscher A, Pletcher SD, Promislow SEL, Tatar M (1995) Genetic variation and aging. Annu Rev Genet 29:553–575PubMedCrossRefGoogle Scholar
  11. Finch CE (1990) Longevity, Senescence, and the Genome. University of Chicago Press, ChicagoGoogle Scholar
  12. Fortini ME, Skupski MP, Boguski MS, Hariharan IK (2000) A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol 150:F23–F29PubMedCrossRefGoogle Scholar
  13. Giannakou ME, Goss M, Junger MA, Hafen E, Leevers SJ et al (2004) Longlived Drosophila with overexpressed dFOXO in adult fat body. Science 305:361PubMedCrossRefGoogle Scholar
  14. Hadler NM (1964) Genetic influence on phototaxis in Drosophila Melanogaster. Biol Bull 126:264–273CrossRefGoogle Scholar
  15. Harman D (2003) The free radical theory of aging. Antioxid Redox Signal 5:557–561PubMedCrossRefGoogle Scholar
  16. Harman D (1995) Free radical theory of aging: Alzheimer's disease pathogenesis. Age 18:97–119CrossRefGoogle Scholar
  17. Hayward DC, Delaney SJ, Campbell HD, Ghysen A, Benzer S et al (1993) The Sluggish-A Gene of Drosophila melanogaster is Expressed in the Nervous System and Encodes Proline Oxidase, a Mitochondrial Enzyme Involved in Glutamate Biosynthesis. Proc Nat Acad Sci USA 90:2979–2983PubMedCrossRefGoogle Scholar
  18. Hernfindez de Salomon C, Spatz HC (1983) Colour vision in Drosophila melanogaster: Wavelength discrimination. J Comp Physiol 150:31–37CrossRefGoogle Scholar
  19. Kang HL, Benzer S, Min KT (2002) Life extension in Drosophila by feeding a drug. Proc Nat Acad Sci USA 99:838–843PubMedCrossRefGoogle Scholar
  20. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V et al (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14:885–890PubMedCentralPubMedCrossRefGoogle Scholar
  21. Kirby K, Jensen LT, Binnington J, Hilliker AJ, Ulloa J, Culotta VC, Phillips JP (2008) Instability of superoxide dismutase 1 of Drosophila in mutants deficient for its cognate copper chaperone. J Biol Chem 283:35393–35401PubMedCrossRefGoogle Scholar
  22. Landis GN, Tower J (2005) Superoxide dismutase evolution and life span regulation. Mech Aging Dev 126:365–379PubMedCrossRefGoogle Scholar
  23. Lin YJ, Seroude L, Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant Methuselah. Science 282:943–946PubMedCrossRefGoogle Scholar
  24. Loeb J, Bancroft FW (1911) Some experiments on the production of mutants in Drosophila. Science 33:781–783PubMedCrossRefGoogle Scholar
  25. Mair W, Goymer P, Pletcher SD, Partridge L (2003) Demography of dietary restriction and death in Drosophila. Science 301:1731–1733Google Scholar
  26. Martinez VG, Javadi CS, Ngo E, Lagow RD, Zhang B (2007) Age-related changes in climbing behavior and neural circuit physiology in Drosophila. Dev Neurobiol 67:778–791PubMedCrossRefGoogle Scholar
  27. Mccord JM, Fridovic I (1969) Superoxide Dismutase an enzymic function for erythrocuprein (Hemocuprein). J Biol Chem 244:6049PubMedGoogle Scholar
  28. Miller GV, Hansen KN, Stark WS (1981) Phototaxis in Drosophila – R1-6 input and interaction among ocellar and compound eye receptors. J Insect Physiol 27:813–819CrossRefGoogle Scholar
  29. Mockett RJ, Sohal RS (2006) Temperature-dependent trade-offs between longevity and fertility in the Drosophila mutant, methuselah. Exp Gerontol 41:566–573PubMedCrossRefGoogle Scholar
  30. Osiewacz HD (1997) Genetic regulation of aging. J Mol Med 75:715–727PubMedCrossRefGoogle Scholar
  31. Paaby AB, Schmidt PS (2008) Functional significance of allelic variation at Methuselah, an aging gene in Drosophila. PLoS One 3:1–8CrossRefGoogle Scholar
  32. Parkes TL, Elia AJ, Dickinson D, Hilliker AJ, Phillips JP, Boulianne GL (1998) Extension of drosophila lifespan by overexpression of human SOD1 in motorneurons. Nat Genet 19:171–174PubMedCrossRefGoogle Scholar
  33. Petrosyan A, Hsieh I, Saberi K (2007) Age-dependent stability of sensorimotor functions in the life-extended Drosophila mutant Methuselah. Behav Genet 37:585–594PubMedCrossRefGoogle Scholar
  34. Petrosyan A, Goncalves OF, Hsieh I, Phillips JP, Saberi K (2012a) Enhanced optomotor efficiency by selective expression of the human gene superoxide dismutase primarily in Drosophila motorneurons. J Neurogenetics 27:59–67Google Scholar
  35. Petrosyan A, Goncalves OF, Hsieh I, Phillips JP, Saberi K (2012b) Enhanced flight and locomotion by selective expression of the human gene SOD1 in Drosophila motorneurons. (submitted)Google Scholar
  36. Phillips JP, Parkes TL, Hilliker AL (2000) Targeted neuronal gene expression and longevity in Drosophila. Exp Gerontol 35:1157–1164PubMedCrossRefGoogle Scholar
  37. Roberts DB (1998) Drosophila: A practical approach, 2nd edn. Oxford University Press, New YorkGoogle Scholar
  38. Rogina B, Helfand SL, Frankel S (2002) Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction. Science 298:1745–1745PubMedCrossRefGoogle Scholar
  39. Rose MR, Vu LN, Park SU, Graves JL (1992) Selection on stress resistance increases longevity in Drosophila-Melanogaster. Exp Gerontol 27:241–250PubMedCrossRefGoogle Scholar
  40. Slawson JB, Kuklin EA, Ejima A, Mukherjee K, Ostrovsky L, Griffith LC (2011) Central regulation of locomotor behavior of drosophila melanogaster depends on a CASK isoform containing CaMK-Like and L27 domains. Genetics 187:171–184PubMedCrossRefGoogle Scholar
  41. Song W, Ranjan R, Dawson-Scully K, Bronk P, Marin L et al (2002) Presynaptic regulation of neurotransmission in Drosophila by the G protein-coupled receptor methuselah. Neuron 36:105–119PubMedCrossRefGoogle Scholar
  42. Strauss R, Hanesch U, Kinkelin M, Wolf R, Heisenberg M (1992) No-bridge of Drosophila melanogaster- Portrait of a structural brain mutant of the central complex. J Neurogenet 8:125–155PubMedCrossRefGoogle Scholar
  43. Wang HD, Kazemi-Esfarjani P, Benzer S (2004) Multiple-stress analysis for isolation of Drosophila longevity genes. Proc Nat Acad Sci USA 101:12610–12615PubMedCrossRefGoogle Scholar
  44. Wang MC, Bohmann D, Jasper H (2003) JNK signaling confers tolerance to oxidative stress and extends lifespan in Drosophila. Dev Cell 5:811–816PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association 2013

Authors and Affiliations

  • Agavni Petrosyan
    • 1
    • 2
  • Óscar F. Gonçalves
    • 2
    • 4
  • I-Hui Hsieh
    • 3
  • Kourosh Saberi
    • 1
  1. 1.Department of Cognitive SciencesUniversity of CaliforniaIrvineUSA
  2. 2.Neuropsychophysiology Lab, CIPsi, School of PsychologyUniversity of MinhoBragaPortugal
  3. 3.Institute of Cognitive NeuroscienceNational Central UniversityJhongli CityTaiwan
  4. 4.Department of Counseling & Applied Educational PsychologyBouvé College of Health Sciences, Northeastern UniversityBostonUSA

Personalised recommendations