Publications (2)6.48 Total impact
-
Article: MicroRNA in Aging: From Discovery to Biology.
[show abstract] [hide abstract]
ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression of their targets at the post-transcriptional levels. A single miRNA can target up to several hundred mRNAs, thus capable of significantly altering gene expression regulatory networks. In-depth study and characterization of miRNAs has elucidated their critical functions in development, homeostasis, and disease. A link between miRNAs and longevity has been demonstrated in C. elegans, implicating their role in regulation of lifespan and in the aging process. Recent years have witnessed unprecedented technological advances in studies of miRNAs, including ultra-high throughput sequencing technologies that allow comprehensive discovery of miRNAs and their targets. Here we review the latest experimental approaches from the perspective of understanding miRNA gene expression regulatory networks in aging. We provide a methodological work flow that can be employed to discover aging-related miRNAs and their targets, and to functionally validate their roles in aging. Finally, we review the links between miRNAs known to act in the conserved pathways of aging and major aging-related diseases. Taken together, we hope to provide a focused review to facilitate future endeavor of uncovering the functional role of miRNA in aging.Current Genomics 11/2012; 13(7):548-57. · 2.41 Impact Factor -
Article: Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing.
[show abstract] [hide abstract]
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 9.4x108 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.BMC Genomics 07/2012; 13(1):353. · 4.07 Impact Factor
