חיפוש מתקדם
Miskin, R., Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel, Israel
Tirosh, O., Institute of Biochemistry, Food Science and Nutrition, Hebrew Univ. Jerusalem, R., Israel
Pardo, M., Institute of Biochemistry, Food Science and Nutrition, Hebrew Univ. Jerusalem, R., Israel
Zusman, I., Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot 76100, Israel, Israel
Schwartz, B., Institute of Biochemistry, Food Science and Nutrition, Hebrew Univ. Jerusalem, R., Israel
Yahav, S., Institute of Animal Science, Agricultural Research Organization, Bet Dagan, Israel, Israel
Dubnov, G., Department of Pharmaceutics, School of Pharmacy, Hebrew Univ. Jerusalem, J., Israel
Kohen, R., Department of Pharmaceutics, School of Pharmacy, Hebrew Univ. Jerusalem, J., Israel
Caloric restriction (CR) is currently the only therapeutic intervention known to attenuate aging in mammals, but the underlying mechanisms of this phenomenon are still poorly understood. To get more insight into these mechanisms, we took advantage of the αMUPA transgenic mice that previously were reported to spontaneously eat less and live longer compared with their wild-type control mice. Currently, two transgenic lines that eat less are available, thus implicating the transgenic enzyme, i.e. the urokinase-type plasminogen activator (uPA), in causing the reduced appetite. This phenotypic change could have resulted from the ectopic transgenic expression that we detected in the adult αMUPA brain, or alternatively, from a transgenic interference in brain development. Here, we have summarized similarities and differences so far found between αMUPA and calorically restricted mice. Recently, we noted several changes in the αMUPA liver, at the mitochondrial and cellular level, which consistently pointed to an enhanced capacity to induce apoptosis. In addition, αMUPA mice showed a reduced level of serum IGF-1 and a reduced incidence of spontaneously occurring or carcinogen-induced tumors in several tissues. In contrast, αMUPA did not differ from wild type mice in the levels of low molecular weight antioxidants when compared in several tissues at a young or an old age. Overall, the αMUPA model suggests that fine-tuning of the threshold for apoptosis, possibly linked in part to modulation of serum IGF-1 and mitochondrial functions, could play a role in the attenuation of aging in calorically restricted mice. © 2004 Elsevier Ireland Ltd. All rights reserved.
פותח על ידי קלירמאש פתרונות בע"מ -
הספר "אוצר וולקני"
אודות
תנאי שימוש
αMUPA mice: A transgenic model for longevity induced by caloric restriction
126
Miskin, R., Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel, Israel
Tirosh, O., Institute of Biochemistry, Food Science and Nutrition, Hebrew Univ. Jerusalem, R., Israel
Pardo, M., Institute of Biochemistry, Food Science and Nutrition, Hebrew Univ. Jerusalem, R., Israel
Zusman, I., Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot 76100, Israel, Israel
Schwartz, B., Institute of Biochemistry, Food Science and Nutrition, Hebrew Univ. Jerusalem, R., Israel
Yahav, S., Institute of Animal Science, Agricultural Research Organization, Bet Dagan, Israel, Israel
Dubnov, G., Department of Pharmaceutics, School of Pharmacy, Hebrew Univ. Jerusalem, J., Israel
Kohen, R., Department of Pharmaceutics, School of Pharmacy, Hebrew Univ. Jerusalem, J., Israel
αMUPA mice: A transgenic model for longevity induced by caloric restriction
Caloric restriction (CR) is currently the only therapeutic intervention known to attenuate aging in mammals, but the underlying mechanisms of this phenomenon are still poorly understood. To get more insight into these mechanisms, we took advantage of the αMUPA transgenic mice that previously were reported to spontaneously eat less and live longer compared with their wild-type control mice. Currently, two transgenic lines that eat less are available, thus implicating the transgenic enzyme, i.e. the urokinase-type plasminogen activator (uPA), in causing the reduced appetite. This phenotypic change could have resulted from the ectopic transgenic expression that we detected in the adult αMUPA brain, or alternatively, from a transgenic interference in brain development. Here, we have summarized similarities and differences so far found between αMUPA and calorically restricted mice. Recently, we noted several changes in the αMUPA liver, at the mitochondrial and cellular level, which consistently pointed to an enhanced capacity to induce apoptosis. In addition, αMUPA mice showed a reduced level of serum IGF-1 and a reduced incidence of spontaneously occurring or carcinogen-induced tumors in several tissues. In contrast, αMUPA did not differ from wild type mice in the levels of low molecular weight antioxidants when compared in several tissues at a young or an old age. Overall, the αMUPA model suggests that fine-tuning of the threshold for apoptosis, possibly linked in part to modulation of serum IGF-1 and mitochondrial functions, could play a role in the attenuation of aging in calorically restricted mice. © 2004 Elsevier Ireland Ltd. All rights reserved.
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