circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan
Open Access
- 6 December 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in GeroScience
- Vol. 42 (1), 183-199
- https://doi.org/10.1007/s11357-019-00120-z
Abstract
Circular RNAs (circRNAs) are an emerging class of non-coding RNA molecules that are thought to regulate gene expression and human disease. Despite the observation that circRNAs are known to accumulate in older organisms and have been reported in cellular senescence, their role in aging remains relatively unexplored. Here, we have assessed circRNA expression in aging human blood and followed up age-associated circRNA in relation to human aging phenotypes, mammalian longevity as measured by mouse median strain lifespan and cellular senescence in four different primary human cell types. We found that circRNAs circDEF6, circEP300, circFOXO3 and circFNDC3B demonstrate associations with parental longevity or hand grip strength in 306 subjects from the InCHIANTI study of aging, and furthermore, circFOXO3 and circEP300 also demonstrate differential expression in one or more human senescent cell types. Finally, four circRNAs tested showed evidence of conservation in mouse. Expression levels of one of these, circPlekhm1, was nominally associated with lifespan. These data suggest that circRNA may represent a novel class of regulatory RNA involved in the determination of aging phenotypes, which may show future promise as both biomarkers and future therapeutic targets for age-related disease.Funding Information
- Northcott Devon Medical Trust (N/A)
- National Institute on Aging (AG038070)
This publication has 57 references indexed in Scilit:
- The Hallmarks of AgingCell, 2013
- The Subread aligner: fast, accurate and scalable read mapping by seed-and-voteNucleic Acids Research, 2013
- The C. elegans MicroRNA mir-71 Acts in Neurons to Promote Germline-Mediated Longevity through Regulation of DAF-16/FOXOCell Metabolism, 2012
- MicroRegulators come of age in senescenceTrends in Genetics, 2011
- Midlife muscle strength and human longevity up to age 100 years: a 44-year prospective study among a decedent cohortAGE, 2011
- Short‐term dietary restriction and fasting precondition against ischemia reperfusion injury in miceAging Cell, 2010
- Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levelsAging Cell, 2009
- TopHat: discovering splice junctions with RNA-SeqBioinformatics, 2009
- ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networksBioinformatics, 2009
- Meta-analysis of age-related gene expression profiles identifies common signatures of agingBioinformatics, 2009