PAGER, version 1
Research type
Research Study
Full title
Prospective study for the early detection of age-related changes in haematopoiesis
IRAS ID
294540
Contact name
George Vassiliou
Contact email
Sponsor organisation
Cambridge University Hospital NS Foundation Trust and the University of Cambridge
Duration of Study in the UK
4 years, 11 months, 31 days
Research summary
Ageing has an attritional impact on all human tissues including blood. In the first decades of life ~200,000 blood stem cells generate hundreds of billions of blood cells every day, through a coordinated process known as haematopoiesis (blood formation). Recent advances have shown that haematopoiesis undergoes a dramatic decline with a rapid reduction in the number of active blood stem cells. As a result, by the age of ~80 years, less than a few hundred stem cells continue to contribute to blood formation in most people. This is in large part a consequence of the accumulation of somatic DNA mutations, a fate that befalls all cells including blood stem cells. Despite the reduction in their numbers, the remaining stem cells are able to expand and "work harder" to meet the body's demands. However, the quantity and quality of mature blood cells they produce deteriorate, resulting in a reduction in the blood's ability to carry out its functions. Certain types of DNA mutations can also initiate a process of clonal proliferation that can, in rare cases, lead to the development of pre-leukaemia or leukaemia.
Here, we propose to investigate how ageing and DNA mutations affect blood stem function in order to:
1) understand how DNA mutations and other non-mutation factors affect normal and premature blood ageing;
2) improve our ability to identify the few individuals at risk of developing leukaemia and related disorders, in order to support efforts to prevent this.To do this, we will establish a longitudinal cohort of adult individuals and monitor the behaviour of their blood over at least 5 years. Participants will complete questionnaires and provide blood and other samples for cellular, biochemical, genomic, and immunological studies.
REC name
East of England - Essex Research Ethics Committee
REC reference
23/EE/0021
Date of REC Opinion
16 Mar 2023
REC opinion
Further Information Favourable Opinion