Research Paper|Volume 5, Issue 10|pp 725—740

Age-related changes in microRNA levels in serum

Nicole Noren Hooten¹, Megan Fitzpatrick¹, William H. Wood 3rd², Supriyo De², Ngozi Ejiogu¹, Yongqing Zhang², Julie A. Mattison³, Kevin G. Becker², Alan B. Zonderman¹, Michele K. Evans¹

¹Laboratory of Epidemiology and Population Sciences, National Institutes of Health, Baltimore, MD 21224, USA
²Laboratory of Genetics, National Institutes of Health, Baltimore, MD 21224, USA
³Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA

* * Equal contribution

Received: August 30, 2013Accepted: September 25, 2013Published: September 27, 2013

https://doi.org/10.18632/aging.100603

Copyright: © 2013 Hooten et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

microRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression by targeting specific mRNAs. Altered expression of circulating miRNAs have been associated with age-related diseases including cancer and cardiovascular disease. Although we and others have found an age-dependent decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs), little is known about the role of circulating miRNAs in human aging. Here, we examined miRNA expression in human serum from young (mean age 30 years) and old (mean age 64 years) individuals using next generation sequencing technology and real-time quantitative PCR. Of the miRNAs that we found to be present in serum, three were significantly decreased in 20 older individuals compared to 20 younger individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in humans, these miRNAs are also present at lower levels in the serum of elderly rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs involved in inflammatory pathways and miR-181a was found to correlate negatively with the pro-inflammatory cytokines IL-6 and TNFα and to correlate positively with the anti-inflammatory cytokines TGFβ and IL-10. These results suggest that circulating miRNAs may be a biological marker of aging and could also be important for regulating longevity. Identification of stable miRNA biomarkers in serum could have great potential as a noninvasive diagnostic tool as well as enhance our understanding of physiological changes that occur with age.