BackgroundBrain aging is a complex process that depends on the precise regulation of multiple brain regions; however, the underlying molecular mechanisms behind this process remain to be clarified in non-human primates.ResultsHere, we explore non-human primate brain aging using 547 transcriptomes originating from 44 brain areas in rhesus macaques (Macaca mulatta). We show that expression connectivity between pairs of cerebral cortex areas as well as expression symmetry between the left and right hemispheres both decrease after aging. Although the aging mechanisms across different brain areas are largely convergent, changes in gene expression and alternative splicing vary at diverse genes, reinforcing the complex multifactorial basis of aging. Through gene co-expression network analysis, we identify nine modules that exhibit gain of connectivity in the aged brain and uncovered a hub gene, PGLS, underlying brain aging. We further confirm the functional significance of PGLS in mice at the gene transcription, molecular, and behavioral levels.ConclusionsTaken together, our study provides comprehensive transcriptomes on multiple brain regions in non-human primates and provides novel insights into the molecular mechanism of healthy brain aging.

中文翻译：

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来自 44 个大脑区域的 547 个转录组揭示了非人类灵长类动物衰老大脑的特征

背景大脑衰老是一个复杂的过程，依赖于多个大脑区域的精确调控；然而，这一过程背后的潜在分子机制仍有待在非人类灵长类动物中阐明。结果在这里，我们使用源自恒河猴 (Macaca mulatta) 44 个大脑区域的 547 个转录组来探索非人类灵长类动物的大脑衰老。我们表明，大脑皮层区域对之间的表达连接性以及左右半球之间的表达对称性在衰老后都会降低。尽管不同大脑区域的衰老机制在很大程度上是趋同的，但基因表达和选择性剪接的变化在不同基因上有所不同，从而强化了衰老的复杂多因素基础。通过基因共表达网络分析，我们确定了九个在衰老大脑中表现出连接性的模块，并发现了一个中枢基因 PGLS，它是大脑衰老的潜在因素。我们进一步证实了 PGLS 在基因转录、分子和行为水平上对小鼠的功能意义。 结论 总之，我们的研究提供了非人类灵长类动物多个大脑区域的综合转录组，并为健康大脑衰老的分子机制提供了新的见解.