Investigation Of MicroRNA Expression In Human Serum During The Aging Process

BACKGROUND:MicroRNAs (miRNAs) are a family of small non-coding RNA 18～25 nucleotides in length. The discovery of circulating microRNAs (miRNAs) and their unique concentration profiles in patients with various diseases makes them attractive, novel noninvasive biomarkers for diagnosis. Although serum microRNAs (miRNAs) play essential roles in the diagnosis of various diseases, little is known about circulating miRNAs with age. We investigated serum miRNA profiles in four groups of 123 healthy individuals with different ages to identify circulating miRNAs that changed with senescence; then we established aging biomarkers in serum.METHODS:Solexa sequencing technology was used for an initial miRNA screening of serum samples pooled from 21 healthy Chinese subjects (11 male and 10 female) with an average age of 22 years (y),10 samples with an average age of 40 y,10 ones 59 y, and 9 ones 70 y. Serum samples were obtained from 123 normal people with approximately 31 samples in each age period. A stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted to confirm the concentrations of the miRNAs altered with age.RESULTS:Solexa sequencing demonstrated 10 markedly altered miRNAs in the aging process. And RT-qPCR analysis identified 5 down-regulated miRNAs (miR-29b, miR-106b, miR-130b, miR-142-5p and miR-340) and 3 up-regulated miRNAs (miR-92a, miR-222 and miR-375) with age. Finally, the protein classes, related diseases, molecular functions and participated pathways of the targeted genes were further analyzed and applied to reveal the relevance of aging-associated miRNA regulation in diseases and physiological processes.CONCLUSIONS:The measurement of miRNAs in serum provides a novel, non-invasive approach for the identification of the aging process. Our bioinformatic analyses form a useful knowledge base for genetic counseling and for the potential future development of novel therapeutic treatments of senescence.