BIOLOGY OF AGING ORAL HEALTH AND ANTI-AGING INTERVENTION IN A NON-HUMAN PRIMATE MODEL

Oral health is associated with nutritional intake and overall well-being in elderly populations and progressivelydeteriorates with aging. In addition, salivary gland function, which plays a major role in oral defense, alsodecreases with age. However, the mechanisms involved in this age-related decline have not beencomprehensively studied due to a lack of proper laboratory animal models for studying changes in oral healthwith aging. The common marmoset is a relatively short-lived non-human primate (NHP) that recapitulates manyof the physiological changes that occur in human aging. At the University of Texas Health Science Center at SanAntonio (UTHSCSA), we maintain a cohort of aging marmosets for a study testing whether the anti-aging drugrapamycin, an inhibitor of mTOR signaling, can extend longevity and delay markers of physiological aging in thisspecies. This multiple PI proposal will use this existing cohort of marmosets to establish an aging NHP modelfor studying oral health and salivary gland function and determine whether oral health in aging can be preservedby an anti-aging intervention. Specific Aim (1): Establish the changes in oral health and relationship to generalphysiological function in aging marmosets and test whether inhibition of mTOR improves these outcomes. Wewill document prevalence of caries, periodontal health indices, oral mucosa lesions of young and old animalsand analyze the microbiome of subgingival plaques and cytokine profiles of gingival crevicular fluid. Theoutcomes from this cohort of animals will be used to compare changes in oral health with changes in generalphysiological health and immunological function during aging already being collected in this cohort. All outcomeswill also be measured in rapamycin-treated old marmosets to evaluate the role of mTOR in oral health and age-associated periodontal bone loss. Specific Aim (2) Establish changes in salivary gland function with age in themarmoset and determine whether mTOR inhibition delays these salivary gland outcomes. Whole saliva fromyoung and old marmosets will be collected to measure salivary flow rate, major antimicrobial proteins, salivarycytokine profiles, and the microbiome and document changes in salivary innate and adaptive immunity duringaging. Age-related salivary structural changes will be evaluated by histological analysis of specimens fromcadavers and needle biopsies and live animal imaging. The effect of rapamycin on salivary glandfunction/structure will be assessed and correlation of salivary gland function and general/oral health will also bedetermined. Significance and Innovation: The proposed exploratory study combines expertise from the fieldsof aging and geriatric dentistry to develop a novel NHP model for studying changes in oral health with aging andlinking these changes to general physiological/immunological decline with aging. The successful establishmentof this model, and the effect of an anti-aging intervention, will drive novel pre-clinical intervention trials for oraland other geriatric diseases.