Circulating Microrna Signature Of Genotype-By-Age Interactions In The Long-Lived Ames Dwarf Mouse

Keywords

Aging; Circulating miRNAs; Dwarf mouse; Sequencing; SncRNAs; TRNA halves

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.

Publication Date

12-1-2015

Publication Title

Aging Cell

Volume

14

Issue

6

Number of Pages

1055-1066

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1111/acel.12373

Socpus ID

84954315880 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84954315880

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