Unlike wild-type flies (Fig. 3), La flies show no difference in pacing-induced arrest rate or in arrest-recovery rate following exercise (multivariate regression, treatment: p = 0.8688, Treatment-by-age: p = 0.3784, Fig. 6C).
Exercise-training, however, produced a much more dramatic reduction in age-related mobility decline in Ra flies than in La flies (multivariate regression, treatment effect, p<0.0001; treatment-by-age: p = 0.0023, Fig. 6A).
Despite the already high mobility of these flies, a small, statistically significant, improvement occurred following the exercise course as compared to unexercised La flies (multivariate regression, treatment effect: p<0.0001).
On 5% sucrose, half the amount of sugar in our standard diet, no difference in mobility was observed during the training course (Fig. 5B), although a small, but statistically significant reduction in mobility among the exercised cohort was observed in the two weeks immediately after training was halted (multivariate regression, treatment effect (days 19 29): p<0.0001, Fig. 5B).
On 2.5% sucrose, a level of carbohydrate intake that results in a reduced lifespan, the exercised cohort experienced a small, but significant increase in its age-related mobility decline, in comparison with unexercised controls (multivariate regression, treatment effect (days 19 36): p = 0.0088, Fig. 5C).
Consistent with this idea, exercised y1w67c23 flies displayed a significant impedance of age-related decline in baseline activity, as measured by longitudinal single-fly activity monitoring (multivariate regression, treatment-by-age: p = 0.0365, Fig. 6B).
Indeed, in the multivariate regression analysis, treatment administration frequency was the variable with the strongest association with compliance, with an increased probability of being compliant to a monthly treatment over twofold higher than for a daily treatment.
For exercise treatment, multivariate regression was used to assess treatment by age.
Multivariate regression analysis using treatment failure as the dependent factor and bcl-2, bcl-XL, bax, bak, survivin, tumour differentiation as covariants demonstrated that bcl-2 (P<0.001), bcl-XL (P=0.007) and bax (P=0.014) were independent variables.
Cohorts that began exercising at three weeks or five weeks of age were not significantly different in their rate of age-related mobility decline compared to unexercised cohorts on the machine at the same time (multivariate regression; three-week, treatment-by-age: p = 0.9893; five week, treatment-by-age: p = 0.9545, Fig. 2D,E).
In multivariate regression analysis, this treatment-by-marker interaction remained significant (P=0.005; HR=0.55; 95% CI, 0.36 0.85), along with nodal status, tumour grade/size, patient age, ER, PgR, Ki67 (all as continuous variables); HER1 3 expression; and treatment (Table 1).
