595 0007-4888/03/1366-0595$25.00 © 2003 Plenum Publishing Corporation BIOGERONTOLOGY Effect of Neuronol on Lifespan and Development of Spontaneous Tumors in SAMP-1 Mice with Genetically Accelerated Aging I. G. Popovich, M. A. Zabezhinskii, V. N. Anisimov, A. L. Kovalenko*, A. Yu. Petrov*, A. V. Semenchenko**, and A. I. Yashin** Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 136, No. 12, pp. 674-677, December, 2003 Original article submitted May 6, 2003 Treatment of female SAMP-1 mice with Neuronol (drug containing succinic acid) given with drinking water starting from the age of 2 months during the whole life prolonged the lifespan and markedly reduced mortality of animals aged 1.5-2 years. Neuronol inhibited the develop- ment of spontaneous tumors, primarily lymphomas, and significantly prolonged lifespan in mice with tumors. Long-term treatment with Neuronol had no pathological side effects. Our experiments demonstrated geroprotective and anticarcinogenic activity of Neuronol and safety of its long-term use. Key Words: Neuronol; succinic acid; geroprotective effect; anticarcinogenic effect; SAMP-1 mice Department of Carcinogenesis and Oncogerontology, N. N. Petrov Institute of Oncology, Ministry of Health of Russian Federation; *Poli- san Firm, St. Petersburg; **Max Planck Institute of Demographic Studies of Society, Restock. Address for correspondence: Address for correspondence: Address for correspondence: Address for correspondence: Address for correspondence: aging@mail.ru. Ani- simov V. N. The search for agents preventing untimely aging is a pressing problem of gerontology [6]. Age-associated metabolic rearrangements consist in modification of mitochondrial energetics (inhibition of succinic acid oxidation), which is proven by the data on decreased SDH activity in tissues during aging [5]. Factors acti- vating the system of succinic acid formation and utili- zation in the body can effectively improve its func- tional potentialities. Treatment with succinate-con- taining drugs can prolong the lifespan of laboratory animals [7]. We studied the effect of Neuronol (drug containing succinic acid) on the processes of aging and spontaneous tumor development in mice with ge- netically accelerated aging. SAMP-1 (senescence ac- celerated mouse-prone-1) strain was derived by selec- tion of AKR/J mice [9,11]; it is characterized by in- creased production of reactive oxygen species (ROS) and high level of 8-hydroxyguanine in organs [4,11]. Presumably, mitochondrial electron transporting sys- tem is impaired in SAMP-1 mice [9]. MATERIALS AND METHODS Experiments were carried out on 63 female SAMP-1 mice, belonging to generations 103 and 104 of mice given by Department of Embryology, Biological Fa- culty of Moscow State University, and maintained at N. N. Petrov Institute of Oncology. The animals were kept in plastic cages, 10 per cage, at 21-23 o C at com- mon day/night regimen (12/12 h) on standard granu- lated fodder with free access to water. Neuronol (Poli- san) contained succinic acid (36.5%), piracetam (25.5%), riboxine (25.5%), nicotinamide (7.3%), riboflavine mononucleotide (2.6%), and pyridoxine hydrochloride (2.6%). The drug is a bright yellow powder with as- corbic acid odor, easily dissolved in water. At the age Bulletin of Experimental Biology and Medicine, Vol. 136, No. 6, December, 2003