Dysregulation of astrocytic Aquaporin-1 in the brains of oldest-old rhesus macaques: the NIA caloric restriction study

Aquaporin-1 (AQP1) is a highly conserved water-channel protein, found to be expressed by astrocytes in adult humans and non-human primates (NHPs). Upregulation of cortical AQP1 expression occurs with cancer, injury, and neurodegenerative disease, but minimal information is available about the effects of normative aging on AQP1 expression. This study leverages tissues from the oldest-old rhesus macaques, some greater than 40 years of age, from the National Institute on Aging longitudinal study of caloric restriction (CR). We tested whether AQP1 levels are altered in the NHP brain as a function of diet group, sex, and age. Sections of formaldehyde-fixed prefrontal (PFC) and temporal (TC) cortices from 36 rhesus macaques (both sexes, 22 to 44 years, + / - CR) were immunochemically stained for AQP1, then the percent area of AQP1 staining was regionally measured using ImageJ free-ware. Results showed age-related regional increases of AQP1 expression, with no effect of diet group or sex. Specifically, in the PFC, AQP1 positively-stained area increased with age in multiple subregions. For the TC subregions, AQP1 area coverage was not affected by age, despite having average levels that were greater than in the PFC. The peak expression of AQP1 in astrocytes appeared in clusters across cortical layers in a subgroup of animals 30 + years old. Astrocytic AQP1 dysregulation may contribute to progressive risk of neuropathology with aging.