Long-term treatment with the mTOR inhibitor rapamycin has minor effect on clinical laboratory markers in middle-aged marmosets

Abstract

Interventions to extend lifespan and improve health with increasing age would have significant impact on a growing aged population. There are now several pharmaceutical interventions that extend lifespan in laboratory rodent models with rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) being the most well studied. In this study, we report on the hematological effects in a cohort of middle-aged common marmosets (Callithrix jacchus) that were enrolled in a study to test the effects of daily rapamycin treatment on aging in this species. In addition, we assessed whether sex was a significant factor in either baseline assessment or as an interaction with rapamycin treatment. Among our cohort at baseline, we found few differences in either basic morphology or hematological markers of blood cell counts, metabolism or inflammation between male and female marmosets. After dosing with rapamycin, surprisingly we found trough blood concentrations of rapamycin were significantly lower in female compared to male marmosets. Despite this pharmacological difference, both sexes had only minor changes in cellular blood counts after 9 months of rapamycin. These data then suggest that the potential clinical hematological side effects of rapamycin are not likely outcomes of long-term rapamycin in relatively healthy, middle-aged marmosets.

Keywords: erythrocytes; healthy aging; leukocytes; longevity; mTOR.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1.

Baseline assessments of fasting glucose, cholesterol, triglycerides and C-reactive protein in middle-aged marmosets prior to rapamycin dosing. Filled circles indicate value for individual animal of indicated sex. Bars represent average value for group with error bars of standard error of mean (SEM). Asterisks indicate p

Figure 2.

Concentration of rapamycin in blood for entire cohort and separated by sex. Filled circles indicate value for individual animal of indicated sex. Bars represent average value for group with error bars of standard error of mean (SEM). Asterisks indicate p

Figure 3.

Metabolic and inflammatory marker changes after 9 months rapamycin in male marmosets. Filled circles indicate value for individual animal of indicated group. Rapa-M are males treated with rapamycin, M are control males. Bars represent average value for group with error bars of standard error of mean (SEM).

Figure 4.

Metabolic and inflammatory marker changes after 9 months rapamycin in female marmosets. Filled circles indicate value for individual animal of indicated group. Rapa-F are females treated with rapamycin, F are control females. Bars represent average value for group with error bars of standard error of mean (SEM).