RC1: Pre-Clinical Research Core

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Several interventions have been shown to promote healthy life extension in rodents. However, analogous prospective, interventional lifespan studies in healthy people are extremely challenging. The Pre-clinical Research Core (RC1) of the SA OAIC addresses this barrier by providing the knowledge, skills, and technical support to assist OAIC investigators in using the common marmoset (Callithrix jacchus) as a pre-clinical model for translational geroscience research. RC1 focuses on marmosets as a pre-clinical model for several reasons: a) They are relatively short-lived nonhuman primates; b) marmosets are small (300-500 g), requiring less costs for husbandry and compound administration; c) marmosets can be maintained in their usual social configurations; d) their spectrum of naturally-occurring age-related pathologies is comparable to that of humans; and e) they allow assessment of interventions in tissues that cannot be readily collected in people (e.g. brain, heart, kidney, liver). Reflecting the interest in this model, the NIA recently released an RFA entitled “Characterization of Marmosets as Models of Aging and Age-Related Diseases”. RC1 achieves its mission through the following Specific Aims: 1) Provide OAIC investigators access to a unique colony of aging marmosets; 2) Provide resources required for studying effects of aging interventions on marmoset healthspan; 3) Provide and maintain a bank of tissues from marmosets across the age range; 4) Provide services to assess analytical pharmacology in marmosets; and 5) Support the research training and dissemination missions of the OAIC. During the initial award cycle, RC1 successfully assisted 13 OAIC funded projects and an additional 13 external projects. RC1 provided tissues to 16 more scientists. Other key accomplishment of RC1 include: • Perform the initial characterization of several aging phenotypes of marmosets, including functional changes with age in executive function, kidney pathology, cardiovascular health, immune function, and the microbiome; • Conduct the first study testing whether nonhuman primate lifespan is extended by a pharmaceutical intervention (rapamycin); • Carry out early-phase pharmacology and tolerability studies with metformin, acarbose and 17α-estradiol that will lay the foundation for long-term lifespan and healthspan trials; • Assist OAIC Scholars and pilot grant recipients to successfully obtain funding from several external sources (NIA, NIDCR, and AFAR) to expand and extend their studies with marmosets; and • Enhance the visibility of the marmoset model and promote use of this valuable resource across the country. During the next award cycle, RC1 will support 2 pilot, 1 Scholar and 10 external projects. RC1 also will support two developmental projects (DPs) with highly innovative features: DP1 entitled “Human-marmoset comparative assessment of the role of mTOR in cardiac aging”, and DP2 entitled “Comparative lipidomics of aging”.