Liu Haiying, Nie Xin, Wang Fengwei, Chen Dandan, Zeng Zhuo, Shu Peng, Huang Junjiu
MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
HBN Research Institute and Biological Laboratory, Shenzhen Hujia Technology Co., Ltd., Shenzhen, Guangdong, China.
Front Aging Neurosci. 2024 Dec 5;16:1450337. doi: 10.3389/fnagi.2024.1450337. eCollection 2024.
It is been noted that the expression levels of numerous genes undergo changes as individuals age, and aging stands as a primary factor contributing to age-related diseases. Nevertheless, it remains uncertain whether there are common aging genes across organs or tissues, and whether these aging genes play a pivotal role in the development of age-related diseases.
In this study, we screened for aging genes using RNAseq data of 32 human tissues from GTEx. RNAseq datasets from GEO were used to study whether aging genes drives age-related diseases, or whether anti-aging solutions could reverse aging gene expression.
Aging transcriptome alterations showed that brain aging differ significantly from the rest of the body, furthermore, brain tissues were divided into four group according to their aging transcriptome alterations. Numerous genes were downregulated during brain aging, with functions enriched in synaptic function, ubiquitination, mitochondrial translation and autophagy. Transcriptome analysis of age-related diseases and retarding aging solutions showed that downregulated aging genes in the hippocampus further downregulation in Alzheimer's disease but were effectively reversed by high physical activity. Furthermore, the neuron loss observed during aging was reversed by high physical activity.
The downregulation of many genes is a major contributor to brain aging and neurodegeneration. High levels of physical activity have been shown to effectively reactivate these genes, making it a promising strategy to slow brain aging.
人们已经注意到，随着个体年龄增长，众多基因的表达水平会发生变化，而衰老乃是导致与年龄相关疾病的主要因素。然而，目前仍不确定不同器官或组织之间是否存在共同的衰老基因，以及这些衰老基因在与年龄相关疾病的发展过程中是否发挥关键作用。
在本研究中，我们利用来自GTEx的32种人体组织的RNA测序数据筛选衰老基因。来自GEO的RNA测序数据集用于研究衰老基因是否驱动与年龄相关的疾病，或者抗衰老解决方案是否能够逆转衰老基因的表达。
衰老转录组改变表明，大脑衰老与身体其他部位显著不同，此外，脑组织根据其衰老转录组改变被分为四组。在大脑衰老过程中，许多基因表达下调，其功能富集于突触功能、泛素化、线粒体翻译和自噬。对与年龄相关疾病和延缓衰老解决方案的转录组分析表明，海马体中下调的衰老基因在阿尔茨海默病中进一步下调，但通过高强度体育活动可有效逆转。此外，高强度体育活动可逆转衰老过程中观察到的神经元损失。
许多基因的下调是大脑衰老和神经退行性变的主要原因。高水平的体育活动已被证明能有效重新激活这些基因，使其成为减缓大脑衰老的一种有前景的策略。
