TY - JOUR
T1 - Long-lived αMUPA transgenic mice exhibit increased mitochondrion-mediated apoptotic capacity
AU - Tirosh, Oren
AU - Schwartz, Betty
AU - Zusman, Igor
AU - Kossoy, George
AU - Yahav, Shlomo
AU - Miskin, Ruth
PY - 2004
Y1 - 2004
N2 - Caloric restriction (CR) is currently the only therapeutic intervention known to attenuate aging in mammals, but the mechanisms underlying this phenomenon are still poorly understood. To study this issue, the transgenic model of αMUPA mice, which previously were reported to spontaneously eat less and live longer compared with their wild-type (WT) control mice, were used. Currently, two transgenic lines that eat less are available, thus implicating the transgenic enzyme, that is, the urokinase-type plasminogen activator (uPA), in causing the reduced appetite. Recently, several changes in the αMUPA liver were noted, 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. Overall, the αMUPA model suggests that long-lasting, moderately increased apoptotic capacity, 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.
AB - Caloric restriction (CR) is currently the only therapeutic intervention known to attenuate aging in mammals, but the mechanisms underlying this phenomenon are still poorly understood. To study this issue, the transgenic model of αMUPA mice, which previously were reported to spontaneously eat less and live longer compared with their wild-type (WT) control mice, were used. Currently, two transgenic lines that eat less are available, thus implicating the transgenic enzyme, that is, the urokinase-type plasminogen activator (uPA), in causing the reduced appetite. Recently, several changes in the αMUPA liver were noted, 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. Overall, the αMUPA model suggests that long-lasting, moderately increased apoptotic capacity, 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.
KW - Aging, apoptosis
KW - Caloric restriction
KW - Mitochondria
KW - uPA plasminogen activator
KW - αMUPA transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=3242683327&partnerID=8YFLogxK
U2 - 10.1196/annals.1297.080
DO - 10.1196/annals.1297.080
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C2 - 15247062
AN - SCOPUS:3242683327
SN - 0077-8923
VL - 1019
SP - 439
EP - 442
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -