Long‐term caloric restriction increases apoptosis and decreases cell stress response, despite an elevation in antioxidant enzyme capacity in the skeletal muscle of the Cu/Zn‐SOD mutant G93A mouse, an animal model of ALS Conferences uri icon

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abstract

  • Despite its life‐extending properties, long‐term caloric restriction (CR) hastens clinical onset and shortens life span in the G93A mouse, an animal model of ALS (Hamadeh et al, 2005; Hamadeh and Tarnopolsky, 2005). We previously reported that CR increased lipid peroxidation (MDA) in this model (Patel et al, 2007). We hypothesized that CR would increase apoptosis and decrease cell stress response, with an incomplete compensatory upregulation of antioxidant enzymes. We investigated the effect of long‐term CR on the protein content of antioxidant enzymes (GPx1, GR), and markers of cell stress response (Hsp70) and apoptosis (Bax, caspase 9, cleaved caspase 9) in 99 d quadriceps of G93A mice. Starting at age 40 d, 27 mice were divided into ad libitum (AL, 14; 7 males) or CR (13; 7 males; 60% of AL). GPx1 increased in CR vs. AL mice (37%, P = 0.019) and in CR vs. AL females (56%, P = 0.012), with no change in GR. GPx1/GR was higher in CR vs. AL females only (88%, P = 0.013). Hsp70 was lower in CR vs. AL mice (62%, P = 0.002) and in males vs. females (37%, P = 0.030). Bax was higher in CR vs. AL mice (41%, P = 0.027) and in CR vs. AL females (52%, P = 0.048). Bax/Bcl‐2 was elevated in CR vs. AL mice (68%, P = 0.040) and in CR vs. AL females (2.3‐fold, P = 0.029). There were no differences in caspases. We conclude that CR increases apoptosis in the G93A mouse due to impairment in cell stress response and an incomplete compensatory upregulation of antioxidant enzymes.Grant Funding SourceHamilton Health Sciences Foundation, NSERC, Faculty of Health‐York University

publication date

  • April 2009