title: Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing.
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.
  
  
  CONCLUSIONS
  Our comprehensive miRNA data provide a resource for further studies to identify genetic pathways associated with aging and longevity in humans.
authors: Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Saurabh
authors: S
authors: Gombar
authors: Hwa Jin
authors: HJ
authors: Jung
authors: Feng
authors: F
authors: Dong
authors: Brent
authors: B
authors: Calder
authors: Gil
authors: G
authors: Atzmon
authors: Nir
authors: N
authors: Barzilai
authors: Xiao-Li
authors: XL
authors: Tian
authors: Joris
authors: J
authors: Pothof
authors: Jan H J
authors: JH
authors: Hoeijmakers
authors: Judith
authors: J
authors: Campisi
authors: Jan
authors: J
authors: Vijg
authors: Yousin
authors: Y
authors: Suh
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger