Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing

BMC Genomics

Research Article

Judith Campisi¹  Hwa Jin Jung²  Brent Calder²  Feng Dong²  Jan Vijg³  Nir Barzilai⁴  Gil Atzmon⁴  Yousin Suh⁵  Joris Pothof⁶  Jan HJ Hoeijmakers⁶  Xiao-Li Tian⁷  Saurabh Gombar⁸ 

[1] Buck Institute for Research on Aging, 94945, Novato, CA, USA;Department of Genetics, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Department of Genetics, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Department of Medicine, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Department of Genetics, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Department of Medicine, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Institute for Aging Research, Diabetes Research and Training Center, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Department of Genetics, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Department of Medicine, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Institute for Aging Research, Diabetes Research and Training Center, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;Institute of Aging Research, Guangdong Medical College, 523808, Dongguan, China;Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands;Department of Human Population Genetics, Peking University, 100871, Beijing, China;Department of Systems and Computational Biology, Albert Einstein College of Medicine, 10461, Bronx, NY, USA;

关键词: MicroRNA;    Centenarians;    Aging;    Life span;    Massively parallel sequencing;   

DOI  :  10.1186/1471-2164-13-353

 received in 2012-02-06, accepted in 2012-07-16,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity.ResultsWe employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4 × 108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels, a typical characteristics of saturated miRNA-sequencing. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Gene Ontology analysis of the predicted and validated targets of the 24 differentially expressed miRNAs indicated enrichment of functional pathways involved in cell metabolism, cell cycle, cell signaling, and cell differentiation. A cross sectional expression analysis of the differentially expressed miRNAs in B-cells from Ashkenazi Jewish individuals between the 50th and 100th years of age indicated that expression levels of miR-363* declined significantly with age. Centenarians, however, maintained the youthful expression level. This result suggests that miR-363* may be a candidate longevity-associated miRNA.ConclusionOur comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans.

【 授权许可】

Unknown   
© Gombar et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.