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Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios

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Abstract

Previously, extremely low, nanomolar concentrations of the mitochondria-targeted plastoquinone derivative SkQ1 (10-(6′-plastoquinonyl) decyltriphenylphosphonium) were shown to prolong the lifespan of male and female Drosophila melanogaster by about 10 % (Anisimov et al., Biochemistry (Moscow) 73:1329–1342, 2008). Using long-term monitoring of SkQ1 effects on the Drosophila lifespan, we analyzed different integral parameters of Drosophila survival and mortality under SkQ1 treatment. Meta-analysis was used to evaluate the average SkQ1 effect measured in terms of standard deviation. The effect appeared to be 0.25 for females and 0.18 for males, which corresponds to a low effect by Cohen’s “Rules-of-Thumb”. The SkQ1 effects on the Drosophila lifespan were reproducible over six years and showed no relationship to fluctuations in the mean lifespan of the w 1118 line used in the experiments, methods of preparation and administration of the drug, seasons, or calendar years. Adding SkQ1 to fly food was associated with a reduction in early mortality and a decrease in random variation in lifespan. All survival curves were fitted by Gompertz function. Analysis of the Gompertz function parametric plane demonstrated significant differences between points corresponding to experimental and control cohorts. The Strehler–Mildvan correlations for 11 experiments with females and for 7 experiments with males were calculated. The significant increase in the slope of the regression lines indicated that feeding flies SkQ1 reduced the rate of fall of fly vitality and, consequently, slowed aging. These findings indicated that the SkQ1 effect on lifespan was associated with both elevation of life quality and slowing of aging.

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References

  • Anisimov VN, Mylnikov SV, Khavinson VK (1998) Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats. Mech Ageing Dev 103:123–132

    Article  PubMed  CAS  Google Scholar 

  • Anisimov VN, Bakeeva LE, Egormin PA, Filenko OF, Isakova EF, Manskikh VN, Mikhelson VM, Panteleeva AA, Pasyukova EG, Pilipenko DI, Piskunova TS, Popovich IG, Roshchina NV, Rybina OY, Saprunova VB, Samoylova TA, Semenchenko AV, Skulachev MV, Spivak IM, Tsybul’ko EA, Tyndyk ML, Vyssokikh MY, Yurova MN, Zabezhinsky MA, Skulachev VP (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence. Biochemistry (Moscow) 73:1329–1342

    Article  CAS  Google Scholar 

  • Anisimov VN, Egorov MV, Krasilshchikova MS, Lyamzaev KG, Manskikh VN, Moshkin MP, Novikov EA, Popovich IG, Rogovin KA, Shabalina IG, Shekarova ON, Skulachev MV, Titova TV, Vygodin VA, Vyssokikh MY, Yurova MN, Zabezhinsky MA, Skulachev VP (2011) Effects of the mitochondria-targeted antioxidant SkQ1 on lifespan of rodents. Aging (Albany NY) 3:1110–1119

    CAS  Google Scholar 

  • Brewer GJ (2010) Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories. Exp Gerontol 45:173–179

    Article  PubMed  CAS  Google Scholar 

  • Broughton SJ, Partridge L (2009) Insulin/IGF-like signalling, the central nervous system and aging. Biochem J 418:1–12

    Article  PubMed  CAS  Google Scholar 

  • Broughton SJ, Piper MD, Ikeya T, Bass TM, Jacobson J, Driege Y, Martinez P, Hafen E, Withers DJ, Leevers SJ, Partridge L (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci USA 102:3105–3110

    Article  PubMed  CAS  Google Scholar 

  • Clancy DJ (2008) Variation in mitochondrial genotype has substantial lifespan effects which may be modulated by nuclear background. Aging Cell 7:795–804

    Article  PubMed  CAS  Google Scholar 

  • Copeland JM, Cho J, Lo T Jr, Hur JH, Bahadorani S, Arabyan T, Rabie J, Soh J, Walker DW (2009) Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain. Curr Biol 19:1591–1598

    Article  PubMed  CAS  Google Scholar 

  • De Luca M, Roshina NV, Geiger-Thornsberry GL, Lyman RF, Pasyukova EG, Mackay TFC (2003) Dopa decarboxylase (Ddc) affects variation in Drosophila longevity. Nat Genet 34:429–433

    Article  PubMed  Google Scholar 

  • Emanuel NM, Obukhova LK (1978) Types of experimental delay in aging patterns. Exp Gerontol 13:25–29

    Article  PubMed  CAS  Google Scholar 

  • Erokhin VN, Krementsova AV, Semenov VA, Burlakova EB (2007) Effect of antioxidant beta-(4-hydroxy-3,5-ditertbutylphenyl) propionic acid (phenosan) on the development of malignant neoplasms. Izv Akad Nauk Ser Biol 5:583–590

    PubMed  Google Scholar 

  • Estes S, Coleman-Hulbert AL, Hicks KA, de Haan G, Martha SR, Knapp JB, Smith SW, Stein KC, Denver DR (2011) Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae. BMC Evol Biol 11:11

    Article  PubMed  Google Scholar 

  • Flatt T (2011) Survival costs of reproduction in Drosophila. Exp Gerontol 46:369–375

    Article  PubMed  Google Scholar 

  • Huedo-Medina T, Sanchez-Meca J, Marin-Martinez F, Botella J (2006) Assessing heterogeneity in metaanalysis: Q statistic or I2 index? CHIP Document Paper 19. http://digitalcommons.uconn.edu/chip_docs/19/

  • Izmailov DM, Obukhova LK (2004) Analysis of the life span distribution mode in 128 successive generations of D. melanogaster. Adv Gerontol 15:30–35

    PubMed  CAS  Google Scholar 

  • Kapahi P (2010) Protein synthesis and the antagonistic pleiotropy hypothesis of aging. Adv Exp Med Biol 694:30–37

    Article  PubMed  CAS  Google Scholar 

  • Kenyon C (2010) A pathway that links reproductive status to lifespan in Caenorhabditis elegans. Ann N Y Acad Sci 1204:156–162

    Article  PubMed  CAS  Google Scholar 

  • Krementsova AV, Gorbunova NV (2010) The impact of environment on lifespan distribution dynamics. Autom Remote Control 71:1617–1628

    Article  Google Scholar 

  • Kulaichev AP (2006) Methods and tools for complex data analysis. The Forum, Infra-M, Moscow

    Google Scholar 

  • Lee KS, Iijima-Ando K, Iijima K, Lee WJ, Lee JH, Yu K, Lee DS (2009) JNK/FOXO-mediated neuronal expression of fly homologue of peroxiredoxin II reduces oxidative stress and extends life span. J Biol Chem 284:29454–29461

    Article  PubMed  CAS  Google Scholar 

  • Lin YJ, Seroude L, Benzer S (1998) Extended life-span and stress resistance in the Drosophila mutant methuselah. Science 282:943–946

    Article  PubMed  CAS  Google Scholar 

  • Lints FA, Lints CV, Bullens P, Bourgois M, Delince J (1989) Unexplained variations in life span of the Oregon-R strain of Drosophila melanogaster over a four-year period. Exp Gerontol 24:265–271

    Article  PubMed  CAS  Google Scholar 

  • Lipsey MW, Wilson DB (2001) Practical metaanalysis. Applied social research methods, Series volume 49. Sage, London

  • Magwere T, West M, Riyahi K, Murphy MP, Smoth RAJ, Partrige L (2006) The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech Ageing Dev 127:356–370

    Article  PubMed  CAS  Google Scholar 

  • Markovets AM, Fursova AZ, Kolosova NG (2011) Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression. Plos One 6(7):e21682

    Article  PubMed  CAS  Google Scholar 

  • Orr WC, Radyuk SN, Prabhudesai L, Toroser D, Benes JJ, Luchak JM, Mockett RJ, Rebrin I, Hubbard JG, Sohal RS (2005) Overexpression of glutamate-cysteine ligase extends life span in Drosophila melanogaster. J Biol Chem 280:37331–37338

    Article  PubMed  CAS  Google Scholar 

  • Parkes TL, Hilliker AJ, Phillips JP (1999) Motorneurons, reactive oxygen, and life span in Drosophila. Neurobiol Aging 20:531–535

    Article  PubMed  CAS  Google Scholar 

  • Pérez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A (2009) Is the oxidative stress theory of aging dead? Biochim Biophys Acta 1790:1005–1014

    Article  PubMed  Google Scholar 

  • Rogina B, Reenan RA, Nilsen SP, Helfand SL (2000) Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290:2137–2140

    Article  PubMed  CAS  Google Scholar 

  • Shmookler Reis RJ, Bharill P, Tazearslan C, Ayyadevara S (2009) Extreme-longevity mutations orchestrate silencing of multiple signaling pathways. Biochim Biophys Acta 1790:1075–1083

    Article  PubMed  CAS  Google Scholar 

  • Skorupa DA, Dervisefendic A, Zwiener J, Pletcher SD (2008) Dietary composition specifies consumption, obesity and lifespan in Drosophila melanogaster. Aging Cell 7:478–490

    Article  PubMed  CAS  Google Scholar 

  • Skulachev VP, Antonenko YN, Cherepanov DA, Chernyak BV, Izyumov DS, Khailova LS, Klishin SS, Korshunova GA, Lyamzaev KG, Pletjushkina OY, Roginsky VA, Rokitskaya TI, Severin FF, Severina II, Simonyan RA, Skulachev MV, Sumbatyan NV, Sukhanova EI, Tashlitsky VN, Trendeleva TA, Vyssokikh MY, Zvyagilskaya RA (2010) Prevention of cardiolipin oxidation and fatty acid cycling as two antioxidant mechanisms of cationic derivatives of plastoquinone (SkQs). Biochim Biophys Acta 1797:878–889

    Article  PubMed  CAS  Google Scholar 

  • Stefanova NA, Fursova AZh, Kolosova NG (2010) Behavioral effects induced by mitochondria-targeted antioxidant SkQ1 in Wistar and senescence-accelerated OXYS rats. J Alzheimers Dis 21:479–491

    PubMed  CAS  Google Scholar 

  • Strehler BL, Mildvan AS (1960) General theory of mortality aging. Science 132:14–21

    Article  PubMed  CAS  Google Scholar 

  • Sun J, Folk D, Bradley TJ, Tower J (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161:661–672

    PubMed  CAS  Google Scholar 

  • Tsybul’ko EA, Roshina NV, Rybina OY, Pasyukova EG (2010) Mitochondria_targeted plastoquinone derivative SkQ1 increases early reproduction of Drosophila melanogaster at the cost of early survival. Biochemistry (Moscow) 75:265–268

    Article  Google Scholar 

  • Walker DW, Benzer S (2004) Mitochondrial “swirls” induced by oxygen stress and in the Drosophila mutant hyperswirl. Proc Natl Acad Sci USA 101:10290–10295

    Article  PubMed  CAS  Google Scholar 

  • Walker DW, Muffat J, Benzer S (2006) Overexpression of a Drosophila homolog of apolipoprotein D leads to increased stress resistance and extended lifespan. Curr Biol 16:674–679

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Li Q, Redden DT, Weindruch R, Allison DB (2004) Statistical methods for testing effects on “maximum lifespan”. Mech Ageing Dev 125:629–632

    Article  PubMed  Google Scholar 

  • Wang MC, Bohmann D, Jasper H (2009) JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121:115–125

    Article  Google Scholar 

  • Wong R, Piper MD, Wertheim B, Partridge L (2009) Quantification of food intake in Drosophila. Plos One 4(6):e6063

    Article  PubMed  Google Scholar 

  • Zid BM, Rofers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, Kapahi P (2009) 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139:149–160

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to V. P. Skulachev, V. N. Anisimov, L. S. Yaguzhinsky, I. I. Severina, B. V. Chernyak, N. G. Kolosova, F. F. Severin, M. Y. Vyssokikh, M. V. Skulachev, V. N. Novoseltcev for helpful discussions. The authors would like to thank the anonymous reviewers for their work and constructive criticisms and suggestions. This work was supported by the Research Institute of Mitoengineering of M. V. Lomonosov Moscow State University and the Ministry of Education and Science of RF Program”Scientific and Educational Human Resources of Innovative Russia”, Contract #P317.

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Authors and Affiliations

  1. Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia

    A. V. Krementsova, N. V. Roshina, E. A. Tsybul’ko, O. Y. Rybina, A. V. Symonenko & E. G. Pasyukova

  2. Emmanuel Institute of Biochemical Physics of RAS, ul. Kosygina 4, 119334, Moscow, Russia

    A. V. Krementsova

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  1. A. V. Krementsova
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  2. N. V. Roshina
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  3. E. A. Tsybul’ko
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  4. O. Y. Rybina
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  5. A. V. Symonenko
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  6. E. G. Pasyukova
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Correspondence to E. G. Pasyukova.

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Krementsova, A.V., Roshina, N.V., Tsybul’ko, E.A. et al. Reproducible effects of the mitochondria-targeted plastoquinone derivative SkQ1 on Drosophila melanogaster lifespan under different experimental scenarios. Biogerontology 13, 595–607 (2012). https://doi.org/10.1007/s10522-012-9404-5

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