Caloric Restriction and ALS Figure 9. SOD content in CR vs. AL G93A mice. (A) MnSOD was higher in CR vs. AL (3-fold, P = 0.031; main effect of diet), and in female vs. male (2.5-fold, P = 0.026; main effect of sex) red gastrocnemius. MnSOD was significantly elevated in CR vs. AL females (4-fold, P = 0.015), but not in CR vs. AL males. (B) MnSOD was higher in CR vs. AL white gastrocnemius (78%, P = 0.062; main effect of diet). MnSOD was higher in CR vs. AL females (2.2- fold, P = 0.038). (C) Cu/Zn-SOD was higher in CR vs. AL red gastrocnemius (67%, P = 0.096; main effect of diet). Cu/Zn-SOD was significantly higher in CR vs. AL females (2.6-fold, P = 0.020). (D) There was no change in Cu/Zn-SOD protein content in white gastrocnemius. Data are presented as means 6 SEM. n = 27; AL, 7 males and 7 females; CR, 7 males and 6 females. Asterisks denote significant changes (P#0.05 vs. AL); dagger denotes strong trend (0.05,P#0.1 vs. AL); double-dagger denotes significant changes (P#0.05 vs. AL females). doi:10.1371/journal.pone.0009386.g009 in accordance with the heightened oxidative damage observed in the study by Gursoy et al (2000), which used another animal model with higher basal levels of stress [39]. An increase in oxidative stress under short-term CR depends on the tissue used, age of animal model, duration of restriction, magnitude of restriction and rodent species analyzed. In our G93A mice, 2 mo of CR (60% of AL) increased peroxidative damage to lipids, indicating heightened oxidative stress. Figure 10. Catalase activity in CR vs. AL G93A mice. Catalase enzyme activity remained unchanged in the white gastrocnemius of G93A mice. Data are presented as means 6 SEM. n = 27; AL, 7 males and 7 females; CR, 7 males and 6 females. doi:10.1371/journal.pone.0009386.g010 Figure 11. TNF-a content in CR vs. AL G93A mice. TNF-a was higher in the quadriceps of CR vs. AL mice (52%, P = 0.030; main effect of diet). Data are presented as means 6 SEM. n = 27; AL, 7 males and 7 females; CR, 7 males and 6 females. Asterisks denote significant changes (P#0.05 vs. AL). doi:10.1371/journal.pone.0009386.g011 PLoS ONE | www.plosone.org 11 February 2010 | Volume 5 | Issue 2 | e9386