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. 2017 Mar 17;7:44620.
doi: 10.1038/srep44620.

MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p Are Associated With Median Strain Lifespan in Mice

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Free PMC article

MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p Are Associated With Median Strain Lifespan in Mice

Benjamin P Lee et al. Sci Rep. .
Free PMC article

Abstract

MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3' untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = -0.6447, p = 4.8 × 10-11], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10-8] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10-6]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. MicroRNA expression against lifespan as measured in targeted assessment of all available mouse strains.
Box-and-whisker plots of relative microRNA expression for the 3 microRNAs found to be significantly associated with strain lifespan in the targeted assessment. Strains and median lifespan in days are given on the x-axis, while the y-axis shows mean log-transformed relative expression. Dark grey boxes show data for all mice analyzed, mid-grey boxes show data for young mice only and light grey boxes show data for old mice only. (a,b and c) expression data for miR-203-3p; (d,e and f) miR-664-3p; (g,h and i) miR-708-5p.
Figure 2
Figure 2. Longevity: Age interactions for microRNAs significantly associated with strain lifespan.
This graph shows the relative expression changes in all mouse strains, categorized based on whether the median individual strain lifespan was above or below the median lifespan calculated across all strains, with ‘Average-lived’ being <847.5 days and ‘Long-lived’ >847.5 days. Young mice are 6 months and old mice are 20–22 months old. All changes are shown in relation to the young animals of the average-lived strains. Average-lived/old mice are shown in light grey, long-lived/young in mid-grey and long-lived/old animals in dark grey. Error bars denote the 95% confidence intervals and statistical significance is indicated by stars, where: *p < 0.05, **p < 0.01 and ***p < 0.001.

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