AlphaMUPA 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 alphaMUPA 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 alphaMUPA brain, or alternatively, from a transgenic interference in brain development. Here, we have summarized similarities and differences so far found between alphaMUPA and calorically restricted mice. Recently, we noted several changes in the alphaMUPA liver, at the mitochondrial and cellular level, which consistently pointed to an enhanced capacity to induce apoptosis. In addition, alphaMUPA 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, alphaMUPA 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 alphaMUPA 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.
Miskin
Ruth
R
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel. ruth.miskin@weizmann.ac.il
Tirosh
Oren
O
Pardo
Michal
M
Zusman
Igor
I
Schwartz
Betty
B
Yahav
Shlomo
S
Dubnov
Gal
G
Kohen
Ron
R
D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D017209:Apoptosis; D001921:Brain / Q000378:metabolism; D031204:Caloric Restriction; D004195:Disease Models, Animal; D005247:Feeding Behavior; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D019076:Transgenes; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D000975:Antioxidants; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D014568:Urokinase-Type Plasminogen Activator