Mitochondria-Targeted Plastoquinone Derivatives as Tools to Interrupt Execution of the Aging Program.
5. SkQ1 Prolongs Lifespan and Prevents Development of Traits of Senescence

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V. N. Anisimov¹, L. E. Bakeeva², P. A. Egormin¹, O. F. Filenko³, E. F. Isakova³, V. N. Manskikh⁴, V. M. Mikhelson⁵, A. A. Panteleeva², E. G. Pasyukova⁶, D. I. Pilipenko², T. S. Piskunova¹, I. G. Popovich¹, N. V. Roshchina⁶, O. Yu. Rybina⁶, V. B. Saprunova², T. A. Samoylova³, A. V. Semenchenko¹, M. V. Skulachev⁴, I. M. Spivak⁵, E. A. Tsybul'ko⁶, M. L. Tyndyk¹, M. Yu. Vyssokikh², M. N. Yurova¹, M. A. Zabezhinsky¹, and V. P. Skulachev^2,4,7*

¹Petrov Institute of Oncology, Pesochny pr. 2, 197758 St. Petersburg, Russia

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia; fax: (495) 939-0338; E-mail: skulach@belozesky.msu.ru

³Biological Faculty, Lomonosov Moscow State University, 119991 Moscow, Russia

⁴Mitoengineering Center, Lomonosov Moscow State University, 119991 Moscow, Russia

⁵Institute of Cytology, Russian Academy of Sciences, Tikhoretsky pr. 4, 194064 St. Petersburg, Russia

⁶Institute of Molecular Genetics, Russian Academy of Sciences, pl. Kurchatova 2, 123182 Moscow, Russia

⁷Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received December 29, 2007; Revision received August 15, 2008

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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.

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KEY WORDS: SkQ1, antioxidants, mitochondria, aging, senescence, therapy

DOI: 10.1134/S0006297908120055

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