RGD Reference Report - Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS. - Rat Genome Database

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Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS.

Authors: Patel, Barkha P  Safdar, Adeel  Raha, Sandeep  Tarnopolsky, Mark A  Hamadeh, Mazen J 
Citation: Patel BP, etal., PLoS One. 2010 Feb 24;5(2):e9386. doi: 10.1371/journal.pone.0009386.
RGD ID: 13506805
Pubmed: PMID:20195368   (View Abstract at PubMed)
PMCID: PMC2827549   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0009386   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
amyotrophic lateral sclerosis severityISOBax (Mus musculus)13506805; 13506805 RGD 
amyotrophic lateral sclerosis severityIEP 13506805 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bax  (BCL2 associated X, apoptosis regulator)

Genes (Mus musculus)
Bax  (BCL2-associated X protein)

Genes (Homo sapiens)
BAX  (BCL2 associated X, apoptosis regulator)


Additional Information