Transcriptome-Wide piRNA profiling in Human Brains for Aging Genetic Factors
*Mao Q, Fan , Wang X Department Of Psychosomatic Medicine, People’s Hospital Of Deyang City, Fudan University, Sichuan, China
*Corresponding Author: Mao Q, Fan , Wang X
Department Of Psychosomatic Medicine, People’s Hospital Of Deyang City, Fudan University, Sichuan, China Email:Xiaoyun.Guo@yale.edu
Published on: 2019-08-20
Objective: Piwi-interacting RNAs (piRNAs) represent a molecular feature shared by all non-aging biological systems, including the germ line 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=24 k) 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; 1.9×10-5≤p≤9.9×10-5). 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.
piRNA; brain; gene expression; aging; years of survival; transposable elements (TEs); Alzheimer’s disease
Piwi-interacting RNAs (piRNAs) represent the largest class of non-coding RNAs. Initially discovered and most abundant in germ line cells, piRNAs have also been identified in somatic tissues, including the brain, heart, small intestine, kidney, liver, lung, skeletal muscle and pancreas. Recently, we reported 9,453 piRNAs in human brains and 8,759 in human stomachs, with 103 and 50 piRNAs associated with Alzheimer’s disease (AD) and gastric cancer, respectively. On the basis of functional versatility of piRNAs, we postulate that piRNAs may be related to more phenotypes, including years of survival, in humans. As the organism ages, transposable elements (TEs) in the genome of somatic cells multiply and become increasingly active and mobile, most obviously in neurons. TEs are capable of moving from one genomic locus to another, thereby causing insertional mutations. Both the TE-derived mutation rates and the mortality rates increase exponentially over the adult lifespan, in contrast to the constant rates in association with TE-independent mutations and chemical or physical mutagens, suggesting a decisive mutagenic role of TEs during aging.