Impact of long-term calorie restriction on metabolic homeostasis and age-associated pathologies.

<p>(A) Weight given as average ± SEM of WT and TgTERT mice fed with control or CR diet (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053760#s4" target="_blank">Materials and Methods</a>). One way ANOVA was used to assess statistical significance between the four groups (WT Control vs. Wt CR: p<0.0001; TgTERT Control vs. TgTERT CR: p<0.0001; WT Control vs. TgTERT Control: p = 0.72; WT CR vs. TgTERT CR: p = 0.46). (B and C) Total fat mass of the indicated cohorts was measured at 16 months of diet (B) and 24 months of diet (C). Values are given as average ± SEM, and statistical significance was determined by the two-tailed Student’s t-test. (D and E) Glucose tolerance test (GTT) was performed at 12 months of diet. Integrated AUCs (area under the curve; (D)) and curves (E) are shown. Values are given as average ± SEM, and statistical significance was determined by the two-tailed Student’s t-test. (F) Fasting plasma insulin levels, given as mean ± SEM, was measured in the different cohorts at 12 months of diet. Statistical significance was determined by the two-tailed Student’s t-test. (G) Insulin sensitivity, estimated using the homeostatic model assessment score (HOMA-IR), was performed at 12 months of diet. Values are given as average ± SEM, and statistical significance was determined by the two-tailed Student’s t-test. (H) Femur bone mineral density (BMD) variation through lifetime of WT and TgTERT mice under control and CR diets. Values are given as average ± SEM, and statistical significance was determined by the two-tailed Student’s <i>t</i>-test. (I) Representative DEXA image used for BMD and fat mass calculations. (J) Neuromuscular coordination was quantified as the percentage of mice that pass with success the tightrope test. Numbers above the bars represent the number of mice that successfully pass the test over the total number of mice tested. Student’s <i>t</i>-test was used to assess significance between control and CR mice. Values are given as average ± SEM, and statistical significance was determined by the two-tailed Student’s <i>t</i>-test.