Effects of SkQl on life span and spontaneous carcinogenesis
in female mice of three various strains

M.N. Yurova, T.S. Piskunova,
M.A. Zabezhinski, I.G. Popovich, M.L. Tyndyk,
V.N. Anisimov
Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 197758

According to the Free Radical theory, the oxidative damages to lipids, proteins and nucleic acids increase with age, explaining the mechanism of ageing and age-related processes including cancer. The effect of mitochondria-targeted antioxidant SkQ1 on longevity and spontaneous carcinogenesis had been studied in outbred SHR, inbred 129/Sv and transgenic HER-2/neu female mice. Animals were treated with SkQ1 (0.5 -2,500 nmol/kg/day) added to the drinking water. Age-related dynamics of the body weight and temperature, the amount of drinking water and consumed food, estrous function as well as parameters of the life span and carcinogenesis were measured.
As compared with controls, no difference in body weight or amount of consumed food and water in all mice strains was found. In SHR mice living in an old non-sterile animal house, SkQ1 treatment increased median life span (by 92% at the optimal dose of 5 nmol), maximal life span (by 6% at the dose of 50 nM) and mean life span by 32%, 45% and 35% in 0.5, 5 and 50 nmol SkQ1 groups respectively (p<0.05). In a new animal house, the lifespan of SHR females without SkQ1 was as long as with the optimal SkQ1 in the old animal house and SkQ1 additions failed to induce further lifespan increase. However, SkQ1 prevented the age-dependent disappearance of estrous cycles in SHR mice kept in either old or new animal house. In females of long-lived 129/Sv mice 250 nmol SkQ1 does not change the median lifespan but increased the maximal lifespan by 64 days. No effect of SkQ1 on parameters of lifespan in short-lived HER-2/neu mice dying because of mammary carcinoma was revealed. There was no significant difference in incidence of tumors in SkQ1-treated SHR mice as compared with the control. The tendency to the decrease of uterine, ovarian and liver tumors incidence has been observed in 129/Sv mice exposed to 5 nmol SkQ1.The treatment with 250 nmol of SkQ1 did not influence number of tumor incidences in this strain. The drug had no effect on mammary carcinogenesis in transgenic HER-2/neu. The treatment with SkQ1 significantly (p<0.05) inhibited the incidence of age-associated non-tumor pathologies of SHR mice. These pathologies (various infection diseases) were the main reason of death in the old animal house. Our data suggest geroprotective activity of SkQ1 and safety of its long term use.

Homo Sapiens Liberatus Workshop, Moscow State University, May 2010