title: Genome-wide miRNA signatures of human longevity.
abstract: Little is known about the functions of miRNAs in human longevity. Here, we present the first genome-wide miRNA study in long-lived individuals (LLI) who are considered a model for healthy aging. Using a microarray with 863 miRNAs, we compared the expression profiles obtained from blood samples of 15 centenarians and nonagenarians (mean age 96.4 years) with those of 55 younger individuals (mean age 45.9 years). Eighty miRNAs showed aging-associated expression changes, with 16 miRNAs being up-regulated and 64 down-regulated in the LLI relative to the younger probands. Seven of the eight selected aging-related biomarkers were technically validated using quantitative RT-PCR, confirming the microarray data. Three of the eight miRNAs were further investigated in independent samples of 15 LLI and 17 younger participants (mean age 101.5 and 36.9 years, respectively). Our screening confirmed previously published miRNAs of human aging, thus reflecting the utility of the applied approach. The hierarchical clustering analysis of the miRNA microarray expression data revealed a distinct separation between the LLI and the younger controls (P-value < 10(-5) ). The down-regulated miRNAs appeared as a cluster and were more often reported in the context of diseases than the up-regulated miRNAs. Moreover, many of the differentially regulated miRNAs are known to exhibit contrasting expression patterns in major age-related diseases. Further in silico analyses showed enrichment of potential targets of the down-regulated miRNAs in p53 and other cancer pathways. Altogether, synchronized miRNA-p53 activities could be involved in the prevention of tumorigenesis and the maintenance of genomic integrity during aging.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University, Schittenhelmstraße 12, D-24105 Kiel, Germany.
authors.forename: Abdou
authors.initials: A
authors.lastname: ElSharawy
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.forename: Friederike
authors.initials: F
authors.lastname: Flachsbart
authors.forename: Anke
authors.initials: A
authors.lastname: Wendschlag
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jacobs
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kefer
authors.forename: Thomas
authors.initials: T
authors.lastname: Brefort
authors.forename: Petra
authors.initials: P
authors.lastname: Leidinger
authors.forename: Christina
authors.initials: C
authors.lastname: Backes
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Almut
authors.initials: A
authors.lastname: Nebel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics; D004194:Disease / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs