Author response image 1. Effects of CR on cardiovascular parameters in humans (related to Figure 10).

Twenty male and twenty-two female volunteers participated in a weight loss study involving a 4-week dietary intervention, as described for Figure 9. (A-F) Systolic blood pressure (BP), diastolic BP and heart rate were recorded at weeks 0, 3 and 4. Data are shown as absolute values (A,C,E) or fold-change relative to baseline (B,D,F). Data are presented as mean ± SEM. Significant effects of time, sex, and time*sex interaction were assessed using 2-way ANOVA. (G-I) Simple linear regression of age vs fold-change (week 4 vs week 0) in systolic BP (G), diastolic BP (H) and heart rate (I). For each sex, significant associations between age and outcome (fold-change) are indicated beneath each graph as ‘P, Slope’. ANCOVA was further used to test if the age-outcome relationship differs significantly between males and females. ANCOVA results are reported beneath each graph as ‘P, Slope’ and ‘P, Intercept’ for males vs females (M vs F). In (G), similar slopes but different intercepts show that sex significantly influences changes in systolic BP, but the influence of age does not differ between the sexes. In (H,I) neither slopes nor intercepts differ significantly between males and females, indicating that the age-outcome relationship is similar between the sexes. (J-L) Fold-change (week 4 vs week 0) in systolic BP (J), diastolic BP (K) and heart rate (L) for males vs females separated into younger (<45 years) and older (>45 years) groups. Data are presented as violin plots overlaid with individual data points. Significant effects of age, sex, and age*sex interaction were assessed using 2-way ANOVA with Tukey’s multiple comparisons test. Overall P values for each variable, and their interactions, are shown beneath each graph. Significant differences between comparable groups are indicated by ** (P<0.01).