Transcriptomic approaches to understanding ageing and metabolism in rodents

Andrew Holmes
Ageing is a major cause of diseases in modern society and leads to many age-related diseases. In addition, rising obesity in society increases the likelihood of various diseases. The development of genetic sequencing technologies provides a novel platform to unravel the complexity of ageing and metabolism. The Naked mole-rat (Heterocephalus glaber) is a rodent that is related to mice (Mus musculus) and ages very slowly, and can live for over 30 years without developing cancer. RNAseq analysis
more » ... H. glaber and M. musculus livers identified genes that were under- or over-expressed in H. glaber. Relative qPCR analysis was performed to confirm the expression of highly expressed genes in the naked mole-rat. Adenosine-to-Inosine (A-to-I) RNA editing is a post-transcriptional modification of specific bases that can cause an alteration in amino acid and splicing events. Recent studies indicated a gene-specific decline in RNA editing with age in humans in Cyfip2. Using SOLiD RNAseq, we sequenced the transcriptomes of 6-, 12-, and 28-month old rat cerebral cortex. We identify a conserved RNA editing site in Cog3. Upon analysis of known conserved RNA editing targets, no changes in RNA editing were observed during ageing in the rat. These results highlight the biological differences between rodent model organisms and humans, and their significance in the context of RNA editing and ageing. Dietary restriction of caloric intake is known to increase the lifespan of many species. Physiologically, these animals remain lean and show a later onset of age-related diseases. Through this concept, we were interested in studying Gnasxlm+/p- knockout mice, which remain lean due to hypermetabolism, despite increased food intake. Gnasxlm+/p- mice have a deletion in Gnas, which prevents expression of Xlαs. However, it is not known exactly how the loss of Xlαs exerts this phenotype. Due to its role in homeostasis and localisation of Xlαs expression, RNA from whole hypothalami of wildtype and Gnasxlm+/p- mice were analysed by Illumina RNAseq [...]
doi:10.17638/02010820 fatcat:fnrqub5k4jcnvhov3exjibaj54