PMID- 15625688
OWN - NLM
STAT- MEDLINE
DCOM- 20050310
LR  - 20161124
IS  - 0148-639X (Print)
IS  - 0148-639X (Linking)
VI  - 31
IP  - 2
DP  - 2005 Feb
TI  - Caloric restriction transiently improves motor performance but hastens clinical 
      onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse.
PG  - 214-20
AB  - Caloric restriction (CR) prolongs lifespan in insects, rodents, and nonhuman 
      primates, a process attributed to a reduction in oxidative stress. Transgenic 
      mice that overexpress the mutant human Cu/Zn-superoxide dismutase (SOD1) gene 
      (G93A mice) are an animal model of amyotrophic lateral sclerosis showing 
      progressively lower motor neuron weakness and increased oxidative stress. We 
      investigated the effect of CR on motor performance, clinical onset, disease 
      progression, and lifespan in G93A mice. Starting at 40 days of age, 14 separately 
      caged G93A mice were randomly divided into two groups: ad libitum (AL; n = 6) and 
      calorie-restricted (CR; n = 8) with a diet equal to 60% of AL. The CR mice (mean 
      +/- SEM: 14.0 +/- 0.7 g) weighed 31% less than the AL mice (20.3 +/- 1.0 g) (P = 
      0.0002). From 74 to 93 days of age, the CR mice performed better on the rotarod 
      than the AL mice: fall time, P = 0.039; fall speed, P = 0.009. The CR mice had a 
      faster rate of reaching clinical onset than the AL mice (hazard ratio = 4.3, P = 
      0.0006). The CR and AL mice reached clinical onset of disease at age 99 +/- 1 and 
      110 +/- 2 days, respectively (P = 0.0003), with no significant difference in 
      disease progression. The CR mice tended to reach endpoint sooner than the AL mice 
      (age-specific death: 125 +/- 3 vs. 133 +/- 3 days, respectively, P = 0.09). We 
      conclude that CR diet transiently improves motor performance but hastens clinical 
      onset of disease in G93A mice. These results suggest that CR diet is not a 
      protective strategy for patients with amyotrophic lateral sclerosis (ALS) and 
      hence is contraindicated.
FAU - Hamadeh, Mazen J
AU  - Hamadeh MJ
AD  - Department of Pediatrics, McMaster University Medical Center, Room 4U4, 1200 Main 
      Street West, Hamilton, Ontario L8N 3Z5, Canada.
FAU - Rodriguez, M Christine
AU  - Rodriguez MC
FAU - Kaczor, Jan J
AU  - Kaczor JJ
FAU - Tarnopolsky, Mark A
AU  - Tarnopolsky MA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Muscle Nerve
JT  - Muscle & nerve
JID - 7803146
RN  - EC 1.15.1.1 (SOD1 G93A protein)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/enzymology/*genetics
MH  - Animals
MH  - Caloric Restriction/*methods
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - *Mutation
MH  - Psychomotor Performance/*physiology
MH  - Superoxide Dismutase/*genetics
EDAT- 2004/12/31 09:00
MHDA- 2005/03/11 09:00
CRDT- 2004/12/31 09:00
PHST- 2004/12/31 09:00 [pubmed]
PHST- 2005/03/11 09:00 [medline]
PHST- 2004/12/31 09:00 [entrez]
AID - 10.1002/mus.20255 [doi]
PST - ppublish
SO  - Muscle Nerve. 2005 Feb;31(2):214-20. doi: 10.1002/mus.20255.