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

Saurabh Gombar, Hwa Jin Jung, Feng Dong, Brent Calder, Gil Atzmon, Nir Barzilai, Xiao Li Tian, Joris Pothof, Jan H J Hoeijmakers, Judith Campisi, Jan Vijg, Yousin Suh

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish (US)
Article number353
JournalBMC Genomics
Volume13
Issue number1
DOIs
StatePublished - Jul 31 2012

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High-Throughput Nucleotide Sequencing
MicroRNAs
B-Lymphocytes
Small Untranslated RNA
Gene Ontology
Cell Differentiation
Cell Cycle
Homeostasis
Down-Regulation

Keywords

  • Aging
  • Centenarians
  • Life span
  • Massively parallel sequencing
  • MicroRNA

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing. / Gombar, Saurabh; Jung, Hwa Jin; Dong, Feng; Calder, Brent; Atzmon, Gil; Barzilai, Nir; Tian, Xiao Li; Pothof, Joris; Hoeijmakers, Jan H J; Campisi, Judith; Vijg, Jan; Suh, Yousin.

In: BMC Genomics, Vol. 13, No. 1, 353, 31.07.2012.

Research output: Contribution to journalArticle

Gombar, S, Jung, HJ, Dong, F, Calder, B, Atzmon, G, Barzilai, N, Tian, XL, Pothof, J, Hoeijmakers, JHJ, Campisi, J, Vijg, J & Suh, Y 2012, 'Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing', BMC Genomics, vol. 13, no. 1, 353. https://doi.org/10.1186/1471-2164-13-353
Gombar, Saurabh ; Jung, Hwa Jin ; Dong, Feng ; Calder, Brent ; Atzmon, Gil ; Barzilai, Nir ; Tian, Xiao Li ; Pothof, Joris ; Hoeijmakers, Jan H J ; Campisi, Judith ; Vijg, Jan ; Suh, Yousin. / Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing. In: BMC Genomics. 2012 ; Vol. 13, No. 1.
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AU - Tian, Xiao Li

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AB - 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.

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