Testing Efficacy of Administration of the Antiaging Drug Rapamycin in a Nonhuman Primate, the Common Marmoset

Suzette Tardif, Corinna Ross, Phillip Bergman, Elizabeth Fernandez, Marty Javors, Adam Salmon, Jennifer Spross, Randy Strong, Arlan Richardson

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

This report is the first description of dosing procedures, pharmacokinetics, biochemical action, and general tolerability of the antiaging drug rapamycin in the common marmoset, a small and short-lived monkey. Eudragit-encapsulated rapamycin was given orally to trained marmosets in a short-term (3 weeks) and a long-term (14 months) study. Circulating trough rapamycin levels (mean = 5.2ng/mL; 1.93-10.73 ng/mL) achieved at roughly 1.0 mg/kg/day was comparable to those reported in studies of rodents and within the therapeutic range for humans. Long-term treated animals (6/8) indicated a reduction in mammalian target of rapamycin complex 1 signaling as noted by a decrease in the phospho rpS6 to total rpS6 ratio after 2 weeks of treatment. All long-term treated subjects had detectable concentrations of rapamycin in liver (4.7-19.9 pg/mg) and adipose tissue (2.2-32.8 pg/mg) with reduced mammalian target of rapamycin signaling in these tissues. There was no evidence of clinical anemia, fibrotic lung changes, or mouth ulcers. The observed death rate in the long-term study was as expected given the animals' ages. The ability to rapidly and reliably dose socially housed marmosets with an oral form of rapamycin that is well tolerated and that demonstrates a suppression of the mammalian target of rapamycin pathway leads us to conclude that this species offers a viable model for rapamycin testing to establish safety and efficacy for long-term antiaging intervention.

Original languageEnglish (US)
Pages (from-to)577-588
Number of pages12
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume70
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • Marmoset
  • Nonhuman primate
  • Rapamycin
  • mTOR

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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