Research

Determining the role of exosomes in cellular senescence and ageing

Principal investigator: Ana O'Loghlen
Co-investigator(s): Martin KNIGHT
Funding source(s): BBSRC
 Start: 03-10-2016  /  End: 02-01-2019

The number elderly population in the UK has dramatically increased in the last few decades. As a consequence, conditions associated with ageing, such as cancer, cardiovascular and neurodegenerative diseases, are having a huge impact on the public health system and the UK economy. It is therefore imperative to promote research that will improve our understanding of the mechanisms implicated in the maintenance of health across life. The primarily hallmark of ageing is the decline in the tissue homeostasis. However, the precise basic and cellular mechanisms implicated in the ageing process are not well established, hindering the advances in understanding how healthy ageing happens. 

The organs and tissues in our body are formed by a vast number of cells, which altogether co-ordinate their actions for our body to function properly. However, a number of "abnormal" cells have been found in tissues derived from old patients. These particular cells suffer a growth arrest or lack of proliferation termed "senescence", which is thought to affect how the tissue functions. Senescent cells fail to proliferate, but they manage to communicate with their neighbour cells, mainly through the release of inflammatory proteins. In this application we will focus on a different way of intercellular communication during senescence, the release of small extracellular vesicles, called exosomes. Exosomes contain biological material in the form of proteins, RNA or small RNAs called microRNAs. Exosomes can release their inside content into particular cells, which as a consequence induce phenotypic changes in the target cells. Our preliminary data show that senescent cells secrete a high number of exosomes and, as a consequence, induce senescence in neighbouring cells. This application will explore the molecular mechanisms by which exosomes released from senescent cells induce senescence in neighbouring cells. We will also determine the inside content of these particular exosomes, in addition to the inside content of exosomes secreted by cells donated by elderly patients, to study similarities and differences between both models. Finally, we will focus on the functionality of exosomes using three-dimensional models of skin culture. During this application we will use a range of approaches, including human cell culture, high-resolution imaging techniques, state-of-the-art proteomics and genomics and an in vitro human skin model. Altogether, this project will help understand the mechanisms by which exosomes regulate normal ageing and it will allow to improve human health and wellbeing throughout life.

Further information: https://gtr.ukri.org/projects?ref=BB%2FP000223%2F1