Age-related brain atrophy is not a homogenous process: Different functional brain networks associate differentially with aging and blood factors.
Age-related brain atrophy is not a homogenous process: Different functional brain networks associate differentially with aging and blood factors.
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与年龄相关的大脑萎缩不是一个同质过程：不同的功能性脑网络将与衰老和血液因子不同。
DOI：
10.1073/pnas.2207181119
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发表时间：
2022-12-06
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫学和神经科学领域已经孤立地发展起来，部分原因是认为脑-血屏障是不可渗透的，然而，新发展的衰老科学揭示了慢性高水平的促炎免疫因子加速了大脑的衰老过程。核磁共振扫描发现大脑皮层体积的下降是衰老的标志。我们提取了一个细胞因子时钟（CyClo），它能够根据一组在一生中不断变化的血液蛋白质的浓度来估计生理年龄。典型相关分析表明，不同功能的皮质网络的体积的变化与年龄，性别和CyClo差异，表明某些功能网络的选择性脆弱性循环水平的免疫标记物的老化。衰老的特征是脑容量以40岁后每十年5%的估计速率进行性损失。虽然这些形态学变化，特别是那些影响灰质和颞叶萎缩，是认知能力的预测因子，与衰老的强关联掩盖了潜在的平行，但更具体的作用，个体受试者的生理。在这里，我们研究了一组554名人类受试者，他们使用结构MRI扫描和血液免疫蛋白浓度进行监测。使用机器学习，我们推导出了细胞因子时钟（CyClo），它根据免疫蛋白子集的表达以良好的准确性（平均绝对误差= 6 y）预测年龄。这些蛋白质包括，除其他外，胎盘生长因子（PLGF）和血管内皮生长因子（VEGF），两者都参与血管生成，化学引诱物血管细胞粘附分子1（VCAM-1），典型炎性蛋白白细胞介素-6（IL-6）和肿瘤坏死因子α（TNFα），化学引诱物IP-10（CXCL 10）和嗜酸性粒细胞趋化因子-1（CCL 11），之前与脑部疾病有关年龄、性别和CyClo与大脑中不同功能定义的皮质网络独立相关。年龄主要与躯体运动系统的变化相关，而性别则与额顶叶、腹侧注意力和视觉网络的变化相关。观察到的CyClo和默认模式，边缘系统和背侧注意力网络显着的典型相关性，表明免疫循环蛋白优先影响大脑过程，如集中注意力，情绪，记忆，对社会压力的反应，内部评价，并获得意识。因此，我们确定了大脑衰老的免疫生物标志物，这些生物标志物可能是预防年龄相关认知能力下降的潜在治疗靶点。
The fields of immunology and neuroscience have evolved in isolation, partially justified by the view that the brain–blood barrier is impermeable, however, the newly developing science of aging has revealed that chronic, high levels of proinflammatory immune factors accelerate the aging process in the brain. MRI scans identify a decline in cortical volume as a marker for aging. We extracted a cytokine clock (CyClo) that was able to estimate physiological age based on the concentrations of a set of blood proteins that change throughout life. Canonical correlation analysis reveals that the variability in the volume of different functional cortical networks associates differentially with age, sex, and CyClo, suggesting selective vulnerabilities of certain functional networks to circulating levels of immune markers of aging. Aging is characterized by a progressive loss of brain volume at an estimated rate of 5% per decade after age 40. While these morphometric changes, especially those affecting gray matter and atrophy of the temporal lobe, are predictors of cognitive performance, the strong association with aging obscures the potential parallel, but more specific role, of individual subject physiology. Here, we studied a cohort of 554 human subjects who were monitored using structural MRI scans and blood immune protein concentrations. Using machine learning, we derived a cytokine clock (CyClo), which predicted age with good accuracy (Mean Absolute Error = 6 y) based on the expression of a subset of immune proteins. These proteins included, among others, Placenta Growth Factor (PLGF) and Vascular Endothelial Growth Factor (VEGF), both involved in angiogenesis, the chemoattractant vascular cell adhesion molecule 1 (VCAM-1), the canonical inflammatory proteins interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), the chemoattractant IP-10 (CXCL10), and eotaxin-1 (CCL11), previously involved in brain disorders. Age, sex, and the CyClo were independently associated with different functionally defined cortical networks in the brain. While age was mostly correlated with changes in the somatomotor system, sex was associated with variability in the frontoparietal, ventral attention, and visual networks. Significant canonical correlation was observed for the CyClo and the default mode, limbic, and dorsal attention networks, indicating that immune circulating proteins preferentially affect brain processes such as focused attention, emotion, memory, response to social stress, internal evaluation, and access to consciousness. Thus, we identified immune biomarkers of brain aging which could be potential therapeutic targets for the prevention of age-related cognitive decline.
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中国阿尔茨海默病和帕金森病的患病率：最新系统分析
影响因子：
4.8
作者：
Cui L;Hou NN;Wu HM;Zuo X;Lian YZ;Zhang CN;Wang ZF;Zhang X;Zhu JH
通讯作者：
Zhu JH
DOI：
10.1523/jneurosci.3252-09.2009
发表时间：
2009-12-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Fjell AM;Walhovd KB;Fennema-Notestine C;McEvoy LK;Hagler DJ;Holland D;Brewer JB;Dale AM
通讯作者：
Dale AM
影响因子：
5
作者：
Stout DM;Buchsbaum MS;Spadoni AD;Risbrough VB;Strigo IA;Matthews SC;Simmons AN
通讯作者：
Simmons AN
DOI：
10.1111/j.1749-6632.2009.05118.x
发表时间：
2010-01-01
期刊：
YEAR IN NEUROLOGY 2
影响因子：
--
作者：
Halliday, Glenda Margaret;McCann, Heather
通讯作者：
McCann, Heather
影响因子：
2.4
作者：
Fletcher, Evan;Gavett, Brandon;Mungas, Dan
通讯作者：
Mungas, Dan