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Open Access Highly Accessed Research article

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

Saurabh Gombar1, Hwa Jin Jung2, Feng Dong2, Brent Calder2, Gil Atzmon234, Nir Barzilai234, Xiao-Li Tian5, Joris Pothof6, Jan HJ Hoeijmakers6, Judith Campisi7, Jan Vijg23 and Yousin Suh2348*

Author Affiliations

1 Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA

2 Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA

3 Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA

4 Institute for Aging Research, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

5 Department of Human Population Genetics, Peking University, Beijing 100871, China

6 Department of Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

7 Buck Institute for Research on Aging, Novato, CA 94945, USA

8 Institute of Aging Research, Guangdong Medical College, Dongguan 523808, China

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BMC Genomics 2012, 13:353  doi:10.1186/1471-2164-13-353

Published: 31 July 2012

Abstract

Background

MicroRNAs (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.

Results

We 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.

Conclusion

Our comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans.

Keywords:
MicroRNA; Centenarians; Aging; Life span; Massively parallel sequencing