Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 5. SkQ1 prolongs lifespan and prevents development of traits of senescence

Abstract

Very low (nano- and subnanomolar) concentrations of 10-(6′-plastoquinonyl) decyltriphenylphosphonium (SkQ1) were found to prolong lifespan of a fungus (Podospora anserina), a crustacean (Ceriodaphnia affinis), an insect (Drosophila melanogaster), and a mammal (mouse). In the latter case, median lifespan is doubled if animals live in a non-sterile vivarium. The lifespan increase is accompanied by rectangularization of the survival curves (an increase in survival is much larger at early than at late ages) and disappearance of typical traits of senescence or retardation of their development. Data summarized here and in the preceding papers of this series suggest that mitochondria-targeted antioxidant SkQ1 is competent in slowing down execution of an aging program responsible for development of age-related senescence.

This is a preview of subscription content, access via your institution.

Abbreviations

C12TPP:

dodecyltriphenylphosphonium

MitoQ:

10-(6′-ubiquinonyl) decyltriphenylphosphonium

PQ:

decyl plastoquinone

ROS:

reactive oxygen species

SkQs:

cationic derivatives of plastoquinone or methyl plastoquinone

SkQ1:

10-(6′-plastoquinonyl) decyltriphenylphosphonium

SkQR1:

10-(6′-plastoquinonyl) decylrhodamine 19

TPP:

tetraphenylphosphonium

References

  1. 1.

    Skulachev, V. P. (2007) Biochemistry (Moscow), 72, 1385–1396.

    Article  CAS  Google Scholar 

  2. 2.

    Antonenko, Y. N., Avetisyan, A. V., Bakeeva, L. E., Chernyak, B. V., Chertkov, V. A., Domnina, L. V., Ivanova, O. Yu., Izyumov, D. S., Khailova, L. S., Klishin, S. S., Korshunova, G. A., Lyamzaev, K. G., Muntyan, M. S., Nepryakhina, O. K., Pashkovskaya, A. A., Pletjushkina, O. Yu., Pustovidko, A. V., Roginsky, V. A., Rokitskaya, T. I., Ruuge, E. K., Saprunova, V. B., Severina, I. I., Simonyan, R. A., Skulachev, I. V., Skulachev, M. V., Sumbatyan, N. V., Sviryaeva, I. V., Tashlitsky, V. N., Vassiliev, J. M., Vyssokikh, M. Yu., Yaguzhinsky, L. S., Zamyatnin, A. A., Jr., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1273–1287.

    Article  CAS  Google Scholar 

  3. 3.

    Bakeeva, L. E., Barskov, I. V., Egorov, M. V., Isaev, N. K., Kapelko, V. I., Kazachenko, A. V., Kirpatovsky, V. I., Kozlovsky, S. V., Lakomkin, V. L., Levina, S. V., Pisarenko, O. I., Plotnikov, E. Y., Saprunova, V. B., Serebryakova, L. I., Skulachev, M. V., Stelmashook, E. V., Studneva, I. M., Tskitishvili, O. V., Vasilyeva, A. K., Victorov, I. V., Zorov, D. B., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1288–1299.

    Article  CAS  Google Scholar 

  4. 4.

    Agapova, L. S., Chernyak, B. V., Domnina, L. V., Dugina, V. B., Efimenko, A. Yu., Fetisova, E. K., Ivanova, O. Yu., Kalinina, N. I., Khromova, N. V., Kopnin, B. P., Kopnin, P. B., Korotetskaya, M. V., Lichinitser, M. R., Lukashev, A. L., Pletjushkina, O. Yu., Popova, E. N., Skulachev, M. V., Shagieva, G. S., Stepanova, E. V., Titova, E. V., Tkachuk, V. A., Vasiliev, J. M., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1300–1316.

    Article  CAS  Google Scholar 

  5. 5.

    Neroev, V. V., Archipova, M. M., Bakeeva, L. E., Fursova, A. Zh., Grigorian, E. N., Grishanova, A. Yu., Iomdina, E. N., Ivashchenko, Zh. N., Katargina, L. A., Khoroshilova-Maslova, I. P., Kilina, O. V., Kolosova, N. G., Kopenkin, E. P., Korshunov, S. S., Kovaleva, N. A., Novikova, Yu. P., Philippov, P. P., Pilipenko, D. I., Robustova, O. V., Saprunova, V. B., Senin, I. I., Skulachev, M. V., Sotnikova, L. F., Stefanova, N. A., Tikhomirova, N. K., Tsapenko, I. B., Shchipanova, A. I., Zinovkin, R. A., and Skulachev, V. P. (2008) Biochemistry (Moscow), 73, 1317–1328.

    Article  CAS  Google Scholar 

  6. 6.

    Esser, K. (1974) in Podospora anserina (King, R. C., ed.) Plenum, New York, Vol. 1, pp. 531–551.

    Google Scholar 

  7. 7.

    Borghouts, C., Kimpel, E., and Osiewacz, H. D. (1997) Proc. Natl. Acad. Sci. USA, 94, 10768–10773.

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Anisimov, V. N., Khavinson, V. Kh., Provinsiali, M., Alimova, I. N., Baturin, D. A., Popovich, I. G., Zabezhinski, M. A., Imyanitov, E. N., Mancini, R., and Franceschi, C. (2002) Int. J. Cancer, 101, 7–10.

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Kabak, Ya. M. (1968) Manual in Endocrinology [in Russian], Vysshaya Shkola, Moscow.

    Google Scholar 

  10. 10.

    Anisimov, V. N., Popovich, I. G., and Zabezhinski, M. A. (2007) Meth. Mol. Biol., 371, 227–236.

    Article  CAS  Google Scholar 

  11. 11.

    Dufour, E., Boulay, J., Rincheval, V., and Sainsard-Chanet, A. (2000) Proc. Natl. Acad. Sci. USA, 97, 4138–4143.

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Scheckhuber, C. Q., Erjavec, N., Tinazli, A., Hammann, A., Nystrom, T., and Osiewacz, H. D. (2007) Nat. Cell Biol., 9, 99–105.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Severina, I. I., et al., in preparation.

  14. 14.

    Skulachev, V. P. (1996) Quart. Rev. Biophys., 29, 169–202.

    Article  CAS  Google Scholar 

  15. 15.

    Walker, D. W., and Benzer, S. (2004) Proc. Natl. Acad. Sci. USA, 101, 10290–10295.

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Berstein, L. (2004) Oncoendocrinology: Traditions, Modernity and Prospects [in Russian], Nauka, St. Petersburg.

    Google Scholar 

  17. 17.

    Wei, M., Fabrizio, P., Hu, J., Ge, H., Cheng, C., Li, L., and Longo, V. D. (2008) PLoS Genetics, 4, 139–149.

    Article  CAS  Google Scholar 

  18. 18.

    James, A. M., Cocheme, H. M., and Murphy, M. P. (2005) Mech. Ageing Dev., 126, 982–986.

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Skulachev, V. P. (2005) IUBMB-Life, 57, 305–310.

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Magwere, T., West, M., Riyahi, K., Murphy, M. P., Smith, R. A. J., and Partridge, L. (2006) Mech. Ageing Dev., 127, 356–370.

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Paul, A., Belton, A., Nag, S., Martin, I., Grotewiel, M. S., and Duttarov, A. (2007) Mech. Ageing Dev., 128, 706–716.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Skulachev, V. P. (2005) Vestnik RAN, 75, 831–843.

    Google Scholar 

  23. 23.

    Skulachev, V. P., and Longo, V. D. (2005) Ann. N. Y. Acad. Sci., 1057, 145–164.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Mair, W., Goymer, P., Pletcher, S. D., and Partridge, L. (2003) Science, 301, 1731–1733.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Libert, S., Zwiener, J., Chu, X., Vanvoorhies, W., Roman, G., and Scott, D. (2007) Science, 315, 1133–1137.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Skulachev, V. P. (1999) Biochemistry (Moscow), 64, 1418–1426.

    CAS  Google Scholar 

  27. 27.

    Skulachev, V. P. (1999) Mol. Asp. Med., 20, 139–184.

    Article  CAS  Google Scholar 

  28. 28.

    Skulachev, V. P. (2003) in Topics in Current Genetics (Nystrom, T., and Osiewacz, H. D., eds.) Model Systems in Ageing, Springer-Verlag, Berlin-Heidelberg, Vol. 3, pp. 191–238.

    Google Scholar 

  29. 29.

    Goldsmith, T. C. (2008) J. Theor. Biol., 252, 764–768.

    Article  PubMed  Google Scholar 

  30. 30.

    Lambert, A. J., Boysen, H. M., Buckingham, J. A., Yang, T., Podlutsky, A., Austad, S. N., Kunz, T. H., Buffenstein, R., and Brand, M. D. (2007) Aging Cell, 6, 607–618.

    Article  CAS  PubMed  Google Scholar 

  31. 31.

    Buffenstein, R. (2005) J. Gerontol. Biol. Sci., 60, 1369–1377.

    Google Scholar 

  32. 32.

    Andziak, B., and Buffenstein, R. (2006) Aging Cell, 5, 525–532.

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Andziak, B., O’Connor, T. P., Qi, W., DeWaal, E. M., Pierce, A., Chaudhuri, A. R., van Remmen, H., and Buffenstein, R. (2006) Aging Cell, 5, 463–471.

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Andziak, B., O’Connor, T. P., and Buffenstein, R. (2005) Mech. Ageing Dev., 126, 1206–1212.

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Labinsky, N., Csiszar, A., Orosz, Z., Smith, K., Rivera, A., Buffenstein, R., and Ungvari, Z. (2006) Am. J. Physiol. Heart Circ. Physiol., 291, H2698–H2704.

    Article  Google Scholar 

  36. 36.

    Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Revoldi, P., Pandolfi, P. P., Lanfrancone, L., and Pelicci, P. G. (1999) Nature, 402, 309–313.

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Liu, X., Jiang, N., Hughes, B., Bigras, E., Shoubridge, E., and Hekimi, S. (2006) Gen. Dev., 19, 2424–2434.

    Article  Google Scholar 

  38. 38.

    Chu, H.-P., Merkin, J. J., Grigorian, I. A., Dorovkov, M. V., Clifford, P., Nagele, R. G., Komarova, E. A., Gudkov, A. V., Yen, K., Mobbs, D. E., Harrison, D. E., and Ryazanov, A. G. (2008) (submitted).

  39. 39.

    Park, T. J., Lu, Y., Juttner, R., Smith, E. St. J., Hu, J., Brand, A., Wetzel, C., Milenkovic, N., Erdmann, B., Heppernstall, P. A., Laurito, C. E., Wilson, S. P., and Lewin, G. R. (2008) PLoS Biology, 6, 156–170.

    Article  CAS  Google Scholar 

  40. 40.

    Pawelec, G., and Larbi, A. (2008) Exp. Gerontol., 43, 34–38.

    CAS  PubMed  Google Scholar 

  41. 41.

    Saule, P., Trauet, J., Dutriez, V., Lekeux, V., Dessaint, J. P., and Labalette, M. (2005) Mech. Ageing Dev., 127, 274–281.

    Article  PubMed  Google Scholar 

  42. 42.

    Polyakova, V. O., Kvetnoy, I. M., Khavinson, V. Kh., Maryanovich, A. T., and Konovalov, S. S. (2001) Adv. Gerontol., 8, 50–57.

    Google Scholar 

  43. 43.

    Turker, M. S., and Cummings, D. J. (1987) J. Bacteriol., 169, 454–460.

    CAS  PubMed  Google Scholar 

  44. 44.

    Shabalina, I. G., et al. (in preparation).

  45. 45.

    Trifunovic, A., Wreeenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly, Y. M., Gidlof, S., Oldfors, A., Wilbom, R., Tornell, J., Jacobs, H. T., and Larsson, N.-G. (2004) Nature, 429, 417–423.

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., Morrow, J. D., van Remmen, H., Sedivy, J. M., Yamasoba, T., Tanokura, M., Weindruch, R., Leeuwenburgh, C., and Prolla, T. A. (2005) Science, 309, 481–484.

    Article  CAS  PubMed  Google Scholar 

  47. 47.

    Greaves, L. C., Preston, S. L., Tadrous, P. J., Taylor, R. W., Barron, M. J., Oukrif, D., Leedham, S. J., Deheragoda, M., Sasieni, P., Novelli, M. R., Jankowski, J. A., Turnbull, D. M., Wright, N. A., and McDonald, S. A. (2006) Proc. Natl. Acad. Sci. USA, 103, 714–719.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to V. P. Skulachev.

Additional information

Published in Russian in Biokhimiya, 2008, Vol. 73, No. 12, pp. 1655–1670.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Anisimov, V.N., Bakeeva, L.E., Egormin, P.A. et al. 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 (2008). https://doi.org/10.1134/S0006297908120055

Download citation

Key words

  • SkQ1
  • antioxidants
  • mitochondria
  • aging
  • senescence
  • therapy