Date of Award

5-2023

Document Type

Thesis campus only

Department

Neuroscience

First Advisor

Kimberley A. Phillips

Second Advisor

Kah-Chung Leong

Abstract

The Common marmoset (Callithrix jacchus) is a prominent translational neuroscience and geroscience model that presents promise as a model of human aging and neurodegenerative disease. Marmosets spontaneously exhibit age-associated phenotypes mirroring those of humans such as cognitive decline and amyloid deposition, and have the shortest lifespan among anthropoid primates, positioning the species for longitudinal study. The trajectory of cortisol across the marmoset lifespan was examined via measure of hair cortisol concentration (HCC) in a cohort of 50 captive animals subdivided into five age groups that span the entire marmoset lifespan. We found that infants exhibited higher HCC than all other age groups, females exhibited higher HCC than males, and an overall moderate negative correlation of cortisol with age across the marmoset lifespan. This suggests that marmosets do not display senescence and progressive dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis as they age. An ongoing 10-month pilot study aims to characterize aging profiles in a cohort of seven aged marmosets in terms of neuroinflammation, cognition, and neurodegenerative biomarkers. This will be done via parallel analysis of dynamic PET images using radiotracer [18F]-DPA-714 to quantify microglial activity, two cognitive tasks, and assessment of neurodegenerative blood biomarkers, including glial fibrillary acidic protein (GFAP), and pro-/anti-inflammatory cytokines. These projects aim to further our understanding of the aging process in the common marmoset, with the hope that these findings may be applied to future efforts using marmosets as an model of human aging, serving to identify risk factors for decline associated with aging, and elucidate the underlying mechanisms inherent in normal or pathological decline with age.

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