RNA Binding Proteins, Ageing and Caloric Restriction

Abstract

A globally ageing population means an increase in age-associated diseases with many
facing a lower quality of life and an increased strain on the world’s economy. It is
therefore paramount that the ageing process is more greatly understood to reduce these
detrimental effects. Senescence, the process by which cells permanently cease
replication is suggested as a driving force for the ageing process. While caloric restriction
has been considered as the only robust environmental method available to increase
longevity and reduce age associated disease in a range of model organisms since the
pioneer experiment by McKay et al in 1935. This project seeks to explore the effect of
both ageing and calorie restriction further by investigating changes to the gene
expression profile of the cell using samples from mouse liver tissue. The mice in this
study were fed an ad libitum or calorie restricted diet before being euthanized at
different ages. RNA sequencing data is available from the mouse liver and has here been
probed with the aim of providing insight into the ageing process. The results shown
include the downregulation of Major Urinary Proteins as the only clear trend in genes
showing the most altered expression and yields some interesting questions as to the true
function of major urinary proteins in mice. However, the project then seeks to
understand what is modulating the changes to gene expression, theorising that subtle
changes to RNA binding proteins could allow these diverse proteins to generate the
changes in gene expression seen in the RNA Sequencing analysis. Human dermal
fibroblasts are also used as a model to begin to understand more greatly the role of
SRSF1, a splicing factor, in senescence.