针对衰老遗传因素的人类大脑全转录组piRNA分析
Transcriptome-wide piRNA profiling in human brains for aging genetic factors.
作者信息
Mao Qiao, Fan Longhua, Wang Xiaoping, Lin Xiandong, Cao Yuping, Zheng Chengchou, Zhang Yong, Zhang Huihao, Garcia-Milian Rolando, Kang Longli, Shi Jing, Yu Ting, Wang Kesheng, Zuo Lingjun, Li Chiang-Shan R, Guo Xiaoyun, Luo Xingguang
机构信息
Department of Psychosomatic Medicine, People's Hospital of Deyang City, Deyang, Sichuan 618000, China.
Department of Vascular Surgery, Qingpu Branch, Zhongshan Hospital, Fudan University, Shanghai 201700, China.
出版信息
Jacobs J Genet. 2019;4(1). Epub 2019 Aug 20.
OBJECTIVE
Piwi-interacting RNAs (piRNAs) represent a molecular feature shared by all nonaging biological systems, including the germline and somatic cancer stem cells, which display an indefinite renewal capacity and lifespan-stable genomic integrity and are potentially immortal. Here, we tested the hypothesis that piRNA is a critical genetic determinant of aging in humans.
METHODS
Expression of transcriptome-wide piRNAs (n=24k) was profiled in the human prefrontal cortex of 12 subjects (84.9±9.5, range 68-100, years of age) using microarray technology. We examined the correlation between these piRNAs' expression levels and age, adjusting for covariates including disease status.
RESULTS
A total of 9,453 piRNAs were detected in brain. Including seven intergenic and three intronic piRNAs, ten piRNAs were significantly associated with age after correction for multiple testing (|r|=0.9; 1.9×10≤p≤9.9×10).
CONCLUSION
We conclude that piRNAs might play a potential role in determining the years of survival of humans. The underlying mechanisms might involve the suppression of transposable elements (TEs) and expression regulation of aging-associated genes.
目的
Piwi相互作用RNA（piRNA）是所有非衰老生物系统共有的分子特征，包括生殖系和体细胞癌干细胞，这些细胞具有无限更新能力和寿命稳定的基因组完整性，并且可能是永生的。在此，我们检验了piRNA是人类衰老关键遗传决定因素的假说。
方法
使用微阵列技术对12名受试者（年龄84.9±9.5岁，范围68 - 100岁）的人类前额叶皮质中的全转录组piRNA（n = 24k）表达进行了分析。我们检查了这些piRNA表达水平与年龄之间的相关性，并对包括疾病状态在内的协变量进行了校正。
结果
在大脑中总共检测到9453种piRNA。包括7种基因间piRNA和3种内含子piRNA，经过多重检验校正后，有10种piRNA与年龄显著相关（|r| = 0.9；1.9×10≤p≤9.9×10）。
结论
我们得出结论，piRNA可能在决定人类生存年限方面发挥潜在作用。其潜在机制可能涉及对转座元件（TE）的抑制以及衰老相关基因的表达调控。
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