Stayer-Wilburn Opal, Brown Donald I, Woltjer Randy L, Srinivasan Sathya, Park Byung S, Shultz Penny, Vitantonio Ana, Dimovasili Christina, Vaughan Kelli L, Starost Matthew F, Rosene Douglas, Mattison Julie A, Urbanski Henryk F, Kohama Steven G
Oregon National Primate Research Center, Beaverton, OR, 97006, USA.
Instituto de Biología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
Geroscience. 2025 Feb;47(1):781-793. doi: 10.1007/s11357-024-01431-6. Epub 2024 Nov 28.
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.
水通道蛋白-1（AQP1）是一种高度保守的水通道蛋白，在成年人类和非人类灵长类动物（NHPs）中发现由星形胶质细胞表达。皮质AQP1表达上调与癌症、损伤和神经退行性疾病有关，但关于正常衰老对AQP1表达的影响的信息很少。本研究利用了来自美国国立衰老研究所热量限制（CR）纵向研究中年龄最大的恒河猴（有些超过40岁）的组织。我们测试了NHPs大脑中AQP1水平是否随饮食组、性别和年龄而改变。对36只恒河猴（雌雄皆有，22至44岁，±CR）的甲醛固定前额叶（PFC）和颞叶（TC）皮质切片进行AQP1免疫化学染色，然后使用ImageJ免费软件对AQP1染色的百分比面积进行区域测量。结果显示，AQP1表达随年龄在区域上增加，不受饮食组或性别的影响。具体而言，在PFC中，多个亚区域的AQP1阳性染色面积随年龄增加。对于TC亚区域，尽管其平均水平高于PFC，但AQP1面积覆盖率不受年龄影响。在30岁以上的一组动物中，星形胶质细胞中AQP1的峰值表达出现在跨皮质层的簇中。星形胶质细胞AQP1失调可能导致衰老过程中神经病理学风险的增加。
