What Is MicroRNA, And Can It Help Us Slow The Ageing Process?

The Nobel Prize in Physiology or Medicine has just been awarded jointly to Victor Ambros and Gary Ruvkun for the discovery of microRNA (miRNA for short). These tiny fragments of genetic material forever changed our understanding of how genes are regulated. But what exactly are miRNAs, and why might they be important for the fight against ageing?

How Cells Get Their Identity

Almost every cell in the body contains exactly the same DNA, yet heart cells, kidney cells and brain cells look very different. The reason for this is that while all these cells contain the same set of genes, not all of those genes are active within a given cell type. Cells have many ways of controlling the activity of their genes. Entire sections of the genome can be locked away and made unreadable, but finer control is also available, such as enhancing or suppressing the activity of a gene in response to changes in the environment. The regulation of gene activity without changing the genetic code itself is known as epigenetics, and by the 1990s, scientists mostly thought we had discovered all of the main mechanisms of epigenetic gene regulation.

The Discovery

In the late 1980s, Victor Ambros and Gary Ruvkun were studying two genes involved in the development of C. elegans worms, called lin-4 and lin-14. They knew that lin-4 suppressed the activity of lin-14, but not how. While studying a mutated form of lin-4, Ambros found that it produced an unusually short strand of RNA. RNA is very similar in structure to DNA. Genes usually produce a type of RNA called messenger RNA (mRNA), which is then used as a template to produce the protein that is encoded by the gene. However, the RNA molecule produced by lin-4 did not code for any protein, yet was seemingly responsible for inhibiting lin-14.

By comparing their data, Ambros and Ruvkun were able to figure out what was going on. The genetic sequence of the small RNA produced by lin-4 lined up perfectly with a critical sequence on the mRNA produced by lin-14. This allowed the small RNA sequence to bind to the lin-14 mRNA, preventing it from being used to produce a protein. A new form of RNA – microRNA – had been discovered, and with it, a new way of regulating gene activity.

These findings were published in 1993, but for a while it was thought that miRNAs might be an anomaly exclusive to worms. This was later disproven however, and we now know that human miRNAs exist and are very important for development and implicated in many diseases. Mutations in genes coding for miRNAs can cause congenital conditions, and disruption of gene regulation by miRNAs is involved in cancer.

miRNAs And The Ageing Process

It turns out that miRNAs affect the lifespan of C. elegans worms. Some mutations in miRNA-coding genes, including lin-4, result in shorter lifespans, while others like mir-239 actually result in them living longer. Not only that, but recent research has shown that the expression of most miRNAs decreases as humans age, and that the extent of this decrease is associated with the development of age related diseases and mortality. Scientists have even linked specific miRNAs to cognitive function. 

At the cellular level, researchers have found that numerous miRNAs play a role in suppressing cancer development and regulating cellular senescence. Senescence is a state that occurs when a cell has divided its maximum number of times and is unable to divide any more. These cells accumulate with increasing age and become a problem in large numbers.

These findings raise two questions. Firstly, are changes in miRNA expression responsible for ageing? And secondly, could we harness them somehow to delay the ageing process, for example by using gene therapy to increase the expression of beneficial miRNAs that decline with age? MiRNAs are unlikely to be the whole story when it comes to ageing, as they are part of a larger picture. Ageing comes with a whole host of changes to how gene expression is controlled, collectively referred to as epigenetic alterations. Epigenetic alterations are themselves only one component of how we age. Nevertheless, miRNAs represent an intriguing avenue worthy of exploration.