title: Circulating microRNA signature of genotype-by-age interactions in the long-lived Ames dwarf mouse.
abstract: Recent evidence demonstrates that serum levels of specific miRNAs significantly change with age. The ability of circulating sncRNAs to act as signaling molecules and regulate a broad spectrum of cellular functions implicates them as key players in the aging process. To discover circulating sncRNAs that impact aging in the long-lived Ames dwarf mice, we conducted deep sequencing of small RNAs extracted from serum of young and old mice. Our analysis showed genotype-specific changes in the circulating levels of 21 miRNAs during aging [genotype-by-age interaction (GbA)]. Genotype-by-age miRNAs showed four distinct expression patterns and significant overtargeting of transcripts involved in age-related processes. Functional enrichment analysis of putative and validated miRNA targets highlighted cellular processes such as tumor suppression, anti-inflammatory response, and modulation of Wnt, insulin, mTOR, and MAPK signaling pathways, among others. The comparative analysis of circulating GbA miRNAs in Ames mice with circulating miRNAs modulated by calorie restriction (CR) in another long-lived mouse suggests CR-like and CR-independent mechanisms contributing to longevity in the Ames mouse. In conclusion, we showed for the first time a signature of circulating miRNAs modulated by age in the long-lived Ames mouse.
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA.
authors.forename: Berta
authors.initials: B
authors.lastname: Victoria
authors.affiliation: Department of Biochemistry, University of California at Riverside, Riverside, CA, 92521, USA.|Center for Genetics, Childrens Hospital Oakland Research Institute, Oakland, CA, 94609, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Dhahbi
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, 301 E. Princeton Street, Orlando, FL, 2804, USA.
authors.forename: Yury O
authors.initials: YO
authors.lastname: Nunez Lopez
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Spinel
authors.affiliation: Department of Medical Education, California Northstate University, Elk Grove, CA, USA.
authors.forename: Hani
authors.initials: H
authors.lastname: Atamna
authors.affiliation: Department of Biochemistry, University of California at Riverside, Riverside, CA, 92521, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spindler
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd., Orlando, FL, 32827, USA.|Department of Head and Neck Surgery, The Greater Poland Cancer Centre, 15 Garbary St., 61-866, Poznan, Poland.
authors.forename: Michal M
authors.initials: MM
authors.lastname: Masternak
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D031204:Caloric Restriction; D004393:Dwarfism, Pituitary / Q000235:genetics*; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D017422:Sequence Analysis, DNA; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D007328:Insulin; D035683:MicroRNAs; D051153:Wnt Proteins; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: aging; circulating miRNAs; dwarf mouse; sequencing; sncRNAs; tRNA halves