Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Feb;17(1):e12687.
doi: 10.1111/acel.12687. Epub 2017 Oct 17.

Age-associated microRNA expression in human peripheral blood is associated with all-cause mortality and age-related traits

Tianxiao Huan  1   2 , George Chen  1   2 , Chunyu Liu  1   2 , Anindya Bhattacharya  3 , Jian Rong  4 , Brian H Chen  5 , Sudha Seshadri  6 , Kahraman Tanriverdi  7 , Jane E Freedman  7 , Martin G Larson  1   4 , Joanne M Murabito  1   6 , Daniel Levy  1   2
Affiliations

Age-associated microRNA expression in human peripheral blood is associated with all-cause mortality and age-related traits

Tianxiao Huan et al. Aging Cell. 2018 Feb.

Abstract

Recent studies provide evidence of correlations of DNA methylation and expression of protein-coding genes with human aging. The relations of microRNA expression with age and age-related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole-blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 × 10-4 (Bonferroni-corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age-associated mRNA expression possibly driven by age-associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict 'microRNA age' that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Δage) and found that Δage was associated with all-cause mortality (hazards ratio 1.1 per year difference, P = 4.2 × 10-5 adjusted for sex and chronological age). Additionally, Δage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole-blood microRNA expression profiling. Age-associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age-related diseases.

Keywords: mRNA; aging; cardiometabolic traits; methylation; microRNA; mortality.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Volcano plot of differentially expressed miRNAs in relation to chronological age. Higher Ct values indicate lower miRNA expression levels. Therefore, positive beta values indicate negative associations between miRNA expression and age.
Figure 2
Figure 2
miRNA age vs. chronological age. (A) In the discovery set; (B) in the replication set.
Figure 3
Figure 3
Survival probability by tertiles of miRNA Δage.
Figure 4
Figure 4
Comparison of miRNA Δage, mRNA age, and DNAm age. (A) miRNA age vs. DNAm age; (B) miRNA age vs. mRNA age; (C) mRNA age vs. DNAm age.
See this image and copyright information in PMC

References

    1. Abdi H (2010) Partial least squares regression and projection on latent structure regression (PLS Regression). Wiley Interdiscip. Rev. Comput. Stat. 2, 97–106.
    1. Agarwal V, Bell GW, Nam J‐W, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. Elife 4, e05005. - PMC - PubMed
    1. Almasy L, Blangero J (1998) Multipoint quantitative‐trait linkage analysis in general pedigrees. Am. J. Hum. Genet. 62, 1198–1211. - PMC - PubMed
    1. Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310, 1954–1957. - PubMed
    1. Brunner S, Herndler‐Brandstetter D, Arnold CR, Wiegers GJ, Villunger A, Hackl M, Grillari J, Moreno‐Villanueva M, Bürkle A, Grubeck‐Loebenstein B (2012) Upregulation of miR‐24 is associated with a decreased DNA damage response upon etoposide treatment in highly differentiated CD8 + T cells sensitizing them to apoptotic cell death. Aging Cell 11, 579–587. - PMC - PubMed

Publication types

LinkOut - more resources