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

• Published in: American journal of primatology Vol. 81; no. 2; pp. e22927 - n/a
• Main Authors: Sills, Aubrey M., Artavia, Joselyn M., DeRosa, Brian D., Ross, Corinna N., Salmon, Adam B.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2019
• Subjects: Aging; Animal models; Animals; Blood; Blood cells; Blood Cells - drug effects; Callithrix - blood; Clinical indicators; Cytology; Dosage; erythrocytes; Female; healthy aging; Hematology; Inflammation; Inhibitors; Intervention; Laboratories; leukocytes; Life span; longevity; Male; Markers; Metabolism; Morphology; mTOR; Pharmacology; Rapamycin; Sex Factors; Side effects; Sirolimus - adverse effects; Sirolimus - blood; Sirolimus - pharmacology; TOR protein; TOR Serine-Threonine Kinases - antagonists & inhibitors; mTOR; leukocytes; longevity; erythrocytes; healthy aging
• ISSN: 0275-2565; 1098-2345; 1098-2345
• DOI: 10.1002/ajp.22927

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. Middle‐aged male and female marmosets were treated once daily with rapamycin as part of a long‐term longevity study. While both sexes were given the same dose of rapamycin, blood concentrations of rapamycin were significantly lower in female marmosets. Neither sex nor rapamycin had major effects on blood markers after 9 months of treatment suggesting long‐term treatment in healthy subjects is relatively safe.