Gene expression in ageing T cells
The process of ageing is complex and multifactorial. It is not surprising that cell dysfunction, leading to tissue, organ and system deterioration is highly complex. In the drive to find some of the answers, the European project T-CIA studied the ageing of the human immune system and in particular, T lymphocytes. These play a central role in cell-mediated immunity and, as such, are thought to be a crucial factor for healthy ageing. As part of this project, partners at the University of Bologne in collaboration with the Unilever group in Colworth, carried out genomic studies of T cell samples. Groups under investigation included healthy and less healthy young and old donors. The scientists looked into whether there were differences in gene expression between the different groups. This was measured by RNA expression using microarray analysis, a high throughput analysis technique that allows the identification of the molecular products of gene expression. The possibility of analysis of so much data opens up the door to experimental design with regard to statistical and sampling validity. Project partners therefore had to consider variability specific to individuals, that is, intra-individual variation. They compared intra- and inter-individual variation within a group of healthy young individuals and individual variability was expressed using a variance ratio. Another factor that may have interfered with the statistical significance of the findings is the range of T cells and their relative frequency within an individual. Consequently, the researchers assessed the T cell types concerned with immunosenescence as a percentage of two main types of T cell together with their associated memory cells. Furthermore, the scientists were able to extract a list of the most interesting genes, therefore giving rise to a molecular signature for each individual. Preliminary results showed significant differences between the T cell signatures of different subjects that did not seem to change over time. Perhaps the most important contribution to research into the ageing process from these findings is the development of experimental methods. Using these as a base, physiological ageing of the human immune system can be unravelled with the overall aim of development of commercially available anti-ageing interventions.
