Frahm Christiane, Srivastava Akash, Schmidt Silvio, Mueller Jule, Groth Marco, Guenther Madlen, Ji Yuanyuan, Priebe Steffen, Platzer Matthias, Witte Otto W
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Neurobiol Aging. 2017 Apr;52:23-31. doi: 10.1016/j.neurobiolaging.2016.12.016. Epub 2016 Dec 27.
The brain plays a central role in organismal aging but is itself most sensitive to aging-related functional impairments and pathologies. Insights into processes underlying brain aging are the basis to positively impact brain health. Using high-throughput RNA sequencing and quantitative polymerase chain reaction (PCR), we monitored cerebral gene expression in mice throughout their whole lifespan (2, 9, 15, 24, and 30 months). Differentially expressed genes were clustered in 6 characteristic temporal expression profiles, 3 of which revealed a distinct change between 24 and 30 months, the period when most mice die. Functional annotation of these genes indicated a participation in protection against cancer and oxidative stress. Specifically, the most enriched pathways for the differentially expressed genes with higher expression at 30 versus 24 months were found to be glutathione metabolism and chemokine signaling pathway, whereas those lower expressed were enriched in focal adhesion and pathways in cancer. We therefore conclude that brains of very old mice are protected from certain aspects of aging, in particular cancer, which might have an impact on organismal health and lifespan.
大脑在机体衰老过程中起着核心作用，但其本身对与衰老相关的功能损伤和病理变化最为敏感。深入了解大脑衰老的潜在过程是积极影响大脑健康的基础。我们使用高通量RNA测序和定量聚合酶链反应（PCR），在小鼠的整个生命周期（2、9、15、24和30个月）中监测其大脑基因表达。差异表达基因被聚类为6种特征性的时间表达谱，其中3种在24至30个月之间显示出明显变化，这是大多数小鼠死亡的时期。这些基因的功能注释表明它们参与了抗癌和抗氧化应激保护。具体而言，在30个月时表达高于24个月的差异表达基因中，最富集的通路是谷胱甘肽代谢和趋化因子信号通路，而表达较低的基因则富集于粘着斑和癌症相关通路。因此，我们得出结论，非常年老小鼠的大脑在某些衰老方面受到保护，特别是癌症，这可能对机体健康和寿命产生影响。
