Qiao Mao1, Longhua Fan2, Xiaoping Wang3, Xiandong Lin4, Yuping Cao5, Chengchou Zheng6, Yong Zhang7, Huihao Zhang8, Rolando Garcia-Milian9, Longli Kang10, Jing Shi11, Ting Yu11, Kesheng Wang12, Lingjun Zuo13, Chiang-Shan R Li11,13, Xiaoyun Guo13,14, Xingguang Luo11,13. 1. Department of Psychosomatic Medicine, People's Hospital of Deyang City, Deyang, Sichuan 618000, China. 2. Department of Vascular Surgery, Qingpu Branch, Zhongshan Hospital, Fudan University, Shanghai 201700, China. 3. Department of Neurology, Shanghai Tongren Hospital, Shanghai Jiaotong University, Shanghai 200080, China. 4. Laboratory of Radiation Oncology and Radiobiology, Fujian Provincial Cancer Hospital, the Teaching Hospital of Fujian Medical University, Fuzhou, Fujian 350014, China. 5. Department of Psychiatry, Second Xiangya Hospital, Central South University, Changsha 410012, China. 6. Minqing Psychiatric Hospital, Minqing, Fujian 350800, China. 7. Tianjin Mental Health Center, Tianjin 300222, China. 8. Department of Thyroid and Breast Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350001, China. 9. Curriculum & Research Support Department, Cushing/Whitney Medical Library, Yale University School of Medicine, New Haven, CT 06510, USA. 10. Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Diseases of Tibet Autonomous Region, Xizang Minzu University School of Medicine, Xiangyang, Shaanxi 712082, China. 11. Biological Psychiatry Research Center, Beijing Huilongguan Hospital, Beijing 100096, China. 12. Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN 37614, USA. 13. Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA. 14. Shanghai Mental Health Center, Shanghai 200030, China.
Abstract
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; 1.9×10-5≤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.
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; 1.9×10-5≤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.
Entities:
Keywords:
Alzheimer’s disease; aging; brain; gene expression; piRNA; transposable elements (TEs); years of survival
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