Enhancing the marmoset aging model through biomarker development

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Although the common marmoset (Callithrix jacchus) has been used in biomedical research for decades, the lack of crucial tools, specifically developed and validated for use in this species, has hampered further advances. Within the last 10 years, popularity of the marmoset model has increased dramatically, prompted to a large degree by realization of their utility for research focused on aging, neuroscience and transgenic and genomic editing. Many factors make this species an attractive model system including their genetic and physiological similarity to humans, relatively short lifespan, high fertility, rapid development, small size and human-like social structure. Importantly, the rapid life history and high fecundity of marmosets make them a compelling model for transgenic applications such as for Alzheimer’s disease (AD), that are much more appropriate in a nonhuman primate than in a rodent model. The goal of the proposed study is to significantly increase the utility of the common marmoset as a model of aging by addressing several of the major gaps currently hampering development. We have chosen to focus our efforts on the development of biomarkers related to energy metabolism, inflammation, neurodegeneration and frailty; areas that will provide the highest return in terms of broad application of the marmoset aging model. Following successful development and validation of our biomarkers, we will use our new tools to test our overall hypothesis that common marmosets show age-related differences in inflammatory tone that increase metabolic and neurodegenerative disease susceptibility and resembles human aging. To address these identified gaps and prove our overall hypothesis we propose three Specific Aims. Aim 1: To develop low volume circulating biomarkers of energy regulation, inflammation and neurodegeneration. Using state-of-the-art techniques, we will develop and validate low volume assays explicitly for common marmosets in the crucial high interest areas for aging research of energy metabolism, inflammation and neurodegeneration. Aim 2: To develop in vivo brain imaging biomarkers of age-related inflammation and accumulation of β amyloid and tau in common marmosets. Although the common marmoset is a very promising model of age-related neurodegenerative diseases, PET radioligands for inflammation and neurodegenerative disorders such as AD have not been tested in this species. We propose to rectify this by evaluating F18-FEPPA for inflammation and C11-PiB and F18-MK6240, for β amyloid and tau, respectively, for the common marmoset. Aim 3: To develop a common marmoset-specific frailty index to assess biological versus chronological age. We propose to utilize existing data to develop a common marmoset-specific frailty index that can be used across a broad range of studies to determine biological age and effect of treatments/interventions. Given the broad implications to aging research of the areas we address in this proposal, we are confident that the knowledge and techniques garnered through these aims will have far-reaching impact on the utility of the common marmoset aging model.