PMID- 20195368
OWN - NLM
STAT- MEDLINE
DCOM- 20100930
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 2
DP  - 2010 Feb 24
TI  - Caloric restriction shortens lifespan through an increase in lipid peroxidation, 
      inflammation and apoptosis in the G93A mouse, an animal model of ALS.
PG  - e9386
LID - 10.1371/journal.pone.0009386 [doi]
LID - e9386
AB  - Caloric restriction (CR) extends lifespan through a reduction in oxidative 
      stress, delays the onset of morbidity and prolongs lifespan. We previously 
      reported that long-term CR hastened clinical onset, disease progression and 
      shortened lifespan, while transiently improving motor performance in G93A mice, a 
      model of amyotrophic lateral sclerosis (ALS) that shows increased free radical 
      production. To investigate the long-term CR-induced pathology in G93A mice, we 
      assessed the mitochondrial bioenergetic efficiency and oxidative capacity 
      (CS--citrate synthase content and activity, cytochrome c oxidase--COX activity 
      and protein content of COX subunit-I and IV and UCP3-uncoupling protein 3), 
      oxidative damage (MDA--malondialdehyde and PC--protein carbonyls), antioxidant 
      enzyme capacity (Mn-SOD, Cu/Zn-SOD and catalase), inflammation (TNF-alpha), 
      stress response (Hsp70) and markers of apoptosis (Bax, Bcl-2, caspase 9, cleaved 
      caspase 9) in their skeletal muscle. At age 40 days, G93A mice were divided into 
      two groups: Ad libitum (AL; n = 14; 7 females) or CR (n = 13; 6 females), with a 
      diet equal to 60% of AL. COX/CS enzyme activity was lower in CR vs. AL male 
      quadriceps (35%), despite a 2.3-fold higher COX-IV/CS protein content. UCP3 was 
      higher in CR vs. AL females only. MnSOD and Cu/Zn-SOD were higher in CR vs. AL 
      mice and CR vs. AL females. MDA was higher (83%) in CR vs. AL red gastrocnemius. 
      Conversely, PC was lower in CR vs. AL red (62%) and white (30%) gastrocnemius. 
      TNF-alpha was higher (52%) in CR vs. AL mice and Hsp70 was lower (62%) in CR vs. 
      AL quadriceps. Bax was higher in CR vs. AL mice (41%) and CR vs. AL females 
      (52%). Catalase, Bcl-2 and caspases did not differ. We conclude that CR increases 
      lipid peroxidation, inflammation and apoptosis, while decreasing mitochondrial 
      bioenergetic efficiency, protein oxidation and stress response in G93A mice.
FAU - Patel, Barkha P
AU  - Patel BP
AD  - School of Kinesiology and Health Science, York University, Toronto, Ontario, 
      Canada.
FAU - Safdar, Adeel
AU  - Safdar A
FAU - Raha, Sandeep
AU  - Raha S
FAU - Tarnopolsky, Mark A
AU  - Tarnopolsky MA
FAU - Hamadeh, Mazen J
AU  - Hamadeh MJ
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100224
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (SOD1 G93A protein)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/genetics/metabolism/physiopathology
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Blotting, Western
MH  - Body Weight/physiology
MH  - Caloric Restriction/*adverse effects
MH  - Catalase/metabolism
MH  - Disease Models, Animal
MH  - Eating/physiology
MH  - Electron Transport Complex IV/metabolism
MH  - Female
MH  - Humans
MH  - Inflammation/etiology/metabolism/*physiopathology
MH  - Lipid Peroxidation/*physiology
MH  - Longevity/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Transgenic
MH  - Mitochondria/metabolism
MH  - Motor Activity/physiology
MH  - Sex Factors
MH  - Superoxide Dismutase/genetics/metabolism
MH  - Survival Analysis
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC2827549
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/03/03 06:00
MHDA- 2010/10/01 06:00
PMCR- 2010/02/24
CRDT- 2010/03/03 06:00
PHST- 2009/09/16 00:00 [received]
PHST- 2009/11/09 00:00 [accepted]
PHST- 2010/03/03 06:00 [entrez]
PHST- 2010/03/03 06:00 [pubmed]
PHST- 2010/10/01 06:00 [medline]
PHST- 2010/02/24 00:00 [pmc-release]
AID - 09-PONE-RA-12937R1 [pii]
AID - 10.1371/journal.pone.0009386 [doi]
PST - epublish
SO  - PLoS One. 2010 Feb 24;5(2):e9386. doi: 10.1371/journal.pone.0009386.