Abstract # 4585 Poster # 160:

Scheduled for Friday, June 21, 2013 07:00 PM-09:00 PM: Session 21 (SG Foyer ABC) Poster Presentation


HEALTHSPAN EFFECTS OF LONG-TERM RAPAMYCIN DOSING IN MARMOSETS

J. Spross, C. N. Ross, M. Javers, R. Strong, S. Austad and S. D. Tardif
University of Texas Health Science Center San Antonio, Barshop Institute for Longevity and Aging Studies, San Antonio, TX 78245, USA
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     Rapamycin has been proposed as an anti-aging drug as it extends life and healthspan in mice. However, rodents dosed with rapamycin also showed increased metabolic dysfunction, induced glucose intolerance and diabetes. Evaluating the effects of rapamycin in a nonhuman primate model is crucial before considering treatment in elderly human populations. Efficacy studies using common marmosets (Callithrix jacchus) were performed to determine the dosage necessary to maintain adequate blood concentrations of rapamycin. Daily doses of encapsulated rapamycin ranged from 0.001 mg/kg to 1.0 mg/kg, with the highest dose resulting in suppressed phospho-rpS6 expression and circulating concentrations of 6 ng/ml. Long-term impacts were examined by dosing eight marmosets with rapamycin and four with vehicle control; animals were dosed daily for one year. Rapamycin animals displayed significant loss in fat mass (F=8.147, p=0.016) with no significant changes in lean mass. Daily dry matter consumption did not differ between groups. Daily activity counts were significantly decreased in rapamycin animals when compared to controls (F=4.782, p=0.054). Triglyceride concentrations were significantly increased in the treatment group (t=2.671, p=0.037), but remained in the normal range. There was no indication of increased insulin resistance or cognitive differences in rapamycin versus control animals. Rapamycin did not cause adverse physiological side effects that have been noted previously in other animal models or humans; however, significant improvements in healthspan parameters were not observed.