Guest post: miRNA’s in ageing

The following post is written by Jasmine Macgilchrist, a fellow coursemate from the University of Bath. She has written a lovely post about the Human Genome Project, and how this links in with what she was working in during her placement year.

The Human Genome Project

In one of Livvi’s earlier blogs, she spoke about The Human Genome Project (HGP). Before the HGP began, the number of nucleotides in the genome was estimated to be 3 × 109 nucleotides, and the number of genes as 6.7 million. However, over time, these numbers have continually decreased. A report made in 1990 by The joint National Institutes of Health (NIH)/Department of Energy (DOE) estimated the human genome to consist of 100, 000 genes, with genes of length of 30, 000 base pairs long. Upon completion of the human genome project, a lower number of known genes than anticipated were confirmed, between 20000 – 25000.

In order to understand why the number of predicted genes has decreased over time, a definition of a gene is required. A gene is thought to be a region of the genome which encodes for mRNA to be transcribed in to protein. The small number of genes identified by the human genome project lead to the majority of DNA being classified as ‘junk’. However, over the past couple of decades, research has identified the unknown complexity of the human genome through non-coding RNA, transcribed from intragenic regions, allowing for control of protein expression.

Non-coding RNA, ageing and cancer

During my placement, I looked into a group of non-coding RNA’s, known as miRNAs, in relation to ageing of adults and the elderly recently diagnosed with cancer. Early on in my placement, I found that an American research group, led by Frank Slack, were trying to identify miRNA involvement in development, ageing and cancer. Slack’s group were one of the first to identify a key miRNA – let-7 – which has been shown to have conserved expression, and involvement in both cancer and ageing processes. As cancer is predominately a disease that occurs later on in life, and due to the emerging research of miRNA in connection to processes common in ageing and cancer, this spurred my interest in use of a cancer database in order to determine whether there are any miRNA expression changes in human ageing.

Pharmacological relevance of studying miRNAs in ageing

Many miRNAs have been shown to change expression at key life stages, such as development, midlife and old age. Expression profiles of miRNAs are emerging with many controlling known age pathways such as calorie restriction and the main ageing related pathway, insulin and insulin-like growth factor 1 (IGF1) signalling (IISpathway.

In March 2013, a research paper was published in Science, written by Professor David Sinclair, indicating that potentially there may be anti-ageing drugs available on the market within the next 5 years. The drug in question, Resveratrol, is known to target the enzyme SIRT1, an enzyme which is involved in the conserved anti-ageing mechanism, Calorie Restriction (CR). This pathway has been shown to be targeting at various points by miRNAs, so through understanding of how the expression of SIRT1 is controlled by miRNAs could aid in future understanding of the mechanism of action of Resveratrol, which until recently has been widely disputed.

Resveratrol has previously tested in trials for many different diseases implicated with ageing, such as cancer, Alzheimer’s and Parkinson’s diseases. The importance of drugs like Resveratrol may be key to controlling pathways such as CR in midlife, where functional decline is thought to begin, to improve quality of life. This is a key issue in a world where average lifespan has drastically increased over the past century due to improvements in medication and living.

References

http://www.sciencedaily.com/releases/2013/03/130308111312.htm

B. P. Hubbard, A. P. Gomes, H. Dai, J. Li, A. W. Case, T. Considine, T. V. Riera, J. E. Lee, S. Y. E, D. W. Lamming, B. L. Pentelute, E. R. Schuman, L. A. Stevens, A. J. Y. Ling, S. M. Armour, S. Michan, H. Zhao, Y. Jiang, S. M. Sweitzer, C. A. Blum, J. S. Disch, P. Y. Ng, K. T. Howitz, A. P. Rolo, Y. Hamuro, J. Moss, R. B. Perni, J. L. Ellis, G. P. Vlasuk, D. A. Sinclair. Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric ActivatorsScience, 2013; 339 (6124): 1216

Smith-Vikos, T., & Slack, F. J. (2012). MicroRNAs and their roles in aging.Journal of cell science, 125(1), 7-17.

Pertea, M., & Salzberg, S. L. (2010). Between a chicken and a grape: estimating the number of human genes. Genome Biol, 11(5), 206.

 Vogel, F. “A preliminary estimate of the number of human genes.” (1964): 847-847.

 

Written by Livvi Harris

Livvi Harris

I am a first year PhD Wellcome Trust PhD student at the Cambridge Stem Cell Institute currently carrying out a year of rotations, so I can’t quite tell you what my PhD is in yet! I am an ex-pharmacologist (or maybe current?!) from the University of Bath, with 15 months experience of industry after working for the oncology pharmacology team at MedImmune in Cambridge for my placement year.

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