In Search of MicroRNAs Related to Aging

Gene expression, the process by which a protein is produced from the specification of a gene, is complicated and the early steps involve dynamic interactions between RNA sequences. MicroRNAs (miRNAs), for example, are small RNA sequences that regulate gene expression by targeting specific messenger RNAs (mRNAs), sequences that transfer information on the gene into the ribosome where the protein will be built.

A lot of work has gone into looking for genes and gene product proteins relating to aging or longevity, but work on finding microRNAs with the same associations has really only just started in comparison - there are few results to see so far. Here, researchers identify some microRNAs whose levels vary with age:

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.

Link: http://www.impactaging.com/papers/v5/n10/full/100603.html

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