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J Gerontol A Biol Sci Med Sci. 2015 May;70(5):577-87. doi: 10.1093/gerona/glu101. Epub 2014 Jul 19.

Testing efficacy of administration of the antiaging drug rapamycin in a nonhuman primate, the common marmoset.

Author information

1
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio. Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio. tardif@uthscsa.edu.
2
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio. Department of Arts & Sciences, Texas A&M-San Antonio.
3
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio.
4
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio. Geriatric Research, Education and Clinical Center, South Texas Veteran's Health Care System, San Antonio.
5
University of Oklahoma Health Sciences Center and the Oklahoma City VA Medical Center.

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 = 5.2 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.

KEYWORDS:

Marmoset; Nonhuman primate.; Rapamycin; mTOR

PMID:
25038772
PMCID:
PMC4400395
DOI:
10.1093/gerona/glu101
[Indexed for MEDLINE]
Free PMC Article

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