ИСТИНА

MtDNA mutator mice (mice possessing a mtDNA polymerase with poor proof reading) exhibit several features of premature aging [1]. We find that MtDNA mutator mice treated with the mitochondria-targeted antioxidant SkQ1 (plastoquinone linked to triphenylphos-phonium cation through a decyl chain) showed delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, torpor, cessation of the estrous cycles, body weight loss and reduced fat content, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 imply that some problems in the mtDNA mutator mice are related to an enhanced reactive oxygen species (ROS) level. The ROS interact with the highly reactive linoleyl groups mainly on cardiolipin. The marked decrease in cardiolipin content deteriorates mitochondrial function; this physiologically leads to diminished capacity for thermogenesis, and the mtDNA mutator mice become moribund mainly because of the ensuing hypothermia. SkQ1 treatment prevents these events. The SkQ1-treated mice therefore live longer (life-span increased from 290 days to 335 days). These data may be relevant in relation to therapeutic treatment of mitochondrial diseases particularly and aging in general. 1. D. Edgar, I.G. Shabalina, Y. Camara, A. Wredenberg, M.A. Calvaruso,L. Nijtmans, J. Nedergaard, B. Cannon, N.G. Larsson, A. Trifunovic. Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab, 10 (2009) 131–138.