PMID- 12954482
OWN - NLM
STAT- MEDLINE
DCOM- 20040202
LR  - 20190910
IS  - 0531-5565 (Print)
IS  - 0531-5565 (Linking)
VI  - 38
IP  - 9
DP  - 2003 Sep
TI  - Mitochondrion-mediated apoptosis is enhanced in long-lived alphaMUPA transgenic 
      mice and calorically restricted wild-type mice.
PG  - 955-63
AB  - Caloric restriction (CR) can extend the life-span of multiple species and is the 
      only intervention known to attenuate aging in mammals. Mechanisms mediating the 
      CR influence are as yet unclear. To get insight into these mechanisms we took 
      advantage of alphaMUPA transgenic mice that have previously been reported to 
      spontaneously eat less and live longer compared with their wild-type (WT) 
      control. Here we report that mitochondria isolated from young adult alphaMUPA 
      livers showed increased susceptibility to calcium-induced high-amplitude 
      swelling, increased cytochrome c release and enhanced glutathione levels. 
      Furthermore, young adult alphaMUPA mice showed significantly enhanced caspase-3 
      activity in liver homogenates, increased fraction of apoptotic hepatocytes, and a 
      lower level of serum IGF-1. In addition, alphaMUPA mice showed a decreased rate 
      of spontaneously occurring lung tumors at an old age. Short-term (8 weeks) 
      calorically restricted WT mice also showed an increase of mitochondrial swelling 
      and caspase-3 activity compared with ad libitum (AL) fed WT mice. These results 
      provide the first indication that CR can enhance mitochondrion-mediated apoptotic 
      capacity. Collectively, the results are consistent with the possibility that long 
      lasting, moderately increased apoptotic capacity, possibly linked in part to 
      IGF-1 and GSH modulation, could play a role in the CR-induced anti-aging 
      influence in mice.
FAU - Tirosh, Oren
AU  - Tirosh O
AD  - Institute of Biochemistry, Food Science and Nutrition, Hebrew University of 
      Jerusalem, Rehovot 76100, Israel.
FAU - Aronis, Anna
AU  - Aronis A
FAU - Zusman, Igor
AU  - Zusman I
FAU - Kossoy, George
AU  - Kossoy G
FAU - Yahav, Shlomo
AU  - Yahav S
FAU - Shinder, Dima
AU  - Shinder D
FAU - Abramovitz, Rene
AU  - Abramovitz R
FAU - Miskin, Ruth
AU  - Miskin R
LA  - eng
PT  - Journal Article
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - GAN16C9B8O (Glutathione)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Aging/*metabolism/pathology
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Calcium/metabolism
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cytochromes c/metabolism
MH  - Energy Intake/physiology
MH  - Female
MH  - Food Deprivation/*physiology
MH  - Glutathione/physiology
MH  - Hepatocytes/cytology
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Longevity/*physiology
MH  - Lung Neoplasms/prevention & control
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitochondria, Liver/*metabolism/physiology
MH  - Urokinase-Type Plasminogen Activator/genetics
EDAT- 2003/09/05 05:00
MHDA- 2004/02/03 05:00
CRDT- 2003/09/05 05:00
PHST- 2003/09/05 05:00 [pubmed]
PHST- 2004/02/03 05:00 [medline]
PHST- 2003/09/05 05:00 [entrez]
AID - S0531556503001517 [pii]
AID - 10.1016/s0531-5565(03)00151-7 [doi]
PST - ppublish
SO  - Exp Gerontol. 2003 Sep;38(9):955-63. doi: 10.1016/s0531-5565(03)00151-7.