Astrocyte heterogeneity and its relation to aging in the normal human brain remain poorly understood. We here analyzed astrocytes in gray and white matter brain tissues obtained from donors ranging in age between the neonatal period to over 100 years. We show that astrocytes are differently distributed with higher density in the white matter. This regional difference in cellular density becomes less prominent with age. Additionally, we confirm the presence of morphologically distinct astrocytes, with gray matter astrocytes being morphologically more complex. Notably, gray matter astrocytes morphologically change with age, while white matter astrocytes remain relatively consistent in morphology. Using regional mass spectrometry-based proteomics, we did, however, identify astrocyte specific proteins with regional differences in abundance, reflecting variation in cellular density or expression level. Importantly, the expression of some astrocyte specific proteins region-dependently decreases with age. Taken together, we provide insights into region- and age-related differences in astrocytes in the human brain.

中文翻译：

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人脑星形胶质细胞的区域特异性和年龄相关差异


星形胶质细胞的异质性及其与正常人脑衰老的关系仍然知之甚少。我们在这里分析了灰质和白质脑组织中的星形胶质细胞，这些脑组织来自年龄从新生儿期到 100 岁以上的捐赠者。我们发现星形胶质细胞在白质中分布不同，密度较高。随着年龄的增长，细胞密度的区域差异变得不那么明显。此外，我们确认了形态上不同的星形胶质细胞的存在，其中灰质星形胶质细胞的形态更加复杂。值得注意的是，灰质星形胶质细胞的形态随着年龄的增长而变化，而白质星形胶质细胞的形态保持相对一致。然而，使用基于区域质谱的蛋白质组学，我们确实鉴定了具有区域丰度差异的星形胶质细胞特异性蛋白质，反映了细胞密度或表达水平的变化。重要的是，一些星形胶质细胞特异性蛋白的表达随着年龄的增长而区域依赖性地降低。总而言之，我们提供了对人脑星形胶质细胞与区域和年龄相关的差异的见解。