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- Title
Testing Efficacy of Administration of the Antiaging Drug Rapamycin in a Nonhuman Primate, the Common Marmoset.
- Authors
Tardif, Suzette; Ross, Corinna; Bergman, Phillip; Fernandez, Elizabeth; Javors, Marty; Salmon, Adam; Spross, Jennifer; Strong, Randy; Richardson, Arlan
- 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 shortlived 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 = 5.2 ng/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.
- Subjects
AGING prevention; RAPAMYCIN; PHYSIOLOGICAL aspects of aging; MARMOSETS as laboratory animals; PHARMACOKINETICS; IMMUNOSUPPRESSION
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2015, Vol 70, Issue 5, p577
- ISSN
1079-5006
- Publication type
Article
- DOI
10.1093/gerona/glu101