title: Deep sequencing identifies circulating mouse miRNAs that are functionally implicated in manifestations of aging and responsive to calorie restriction.
abstract: MicroRNAs (miRNAs) function to modulate gene expression, and through this property they regulate a broad spectrum of cellular processes. They can circulate in blood and thereby mediate cell-to-cell communication. Aging involves changes in many cellular processes that are potentially regulated by miRNAs, and some evidence has implicated circulating miRNAs in the aging process. In order to initiate a comprehensive assessment of the role of circulating miRNAs in aging, we have used deep sequencing to characterize circulating miRNAs in the serum of young mice, old mice, and old mice maintained on calorie restriction (CR). Deep sequencing identifies a set of novel miRNAs, and also accurately measures all known miRNAs present in serum. This analysis demonstrates that the levels of many miRNAs circulating in the mouse are increased with age, and that the increases can be antagonized by CR. The genes targeted by this set of age-modulated miRNAs are predicted to regulate biological processes directly relevant to the manifestations of aging including metabolic changes, and the miRNAs themselves have been linked to diseases associated with old age. This finding implicates circulating miRNAs in the aging process, raising questions about their tissues of origin, their cellular targets, and their functional role in metabolic changes that occur with aging.
authors.affiliation: Department of Biochemistry, University of California at Riverside, Riverside, CA 92521, USA. jdhahbi@ucr.edu
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Dhahbi
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spindler
authors.forename: Hani
authors.initials: H
authors.lastname: Atamna
authors.forename: Amy
authors.initials: A
authors.lastname: Yamakawa
authors.forename: Noel
authors.initials: N
authors.lastname: Guerrero
authors.forename: Dario
authors.initials: D
authors.lastname: Boffelli
authors.forename: Patricia
authors.initials: P
authors.lastname: Mote
authors.forename: David I K
authors.initials: DI
authors.lastname: Martin
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D051379:Mice; D035683:MicroRNAs / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs