We know that sleep and body clocks are adversely affected by shift work, light at night, and the extension of activities late into the evening. This is known as 'sleep and circadian rhythm disruption', or SCRD. But sleep and body clocks are also often disturbed by cardiometabolic disease. This can create a vicious cycle whereby people with SCRD are at risk of developing cardiometabolic disease, and if they go on to develop the disease, this in itself can worsen their sleep and body clock problems.
This is an amazing opportunity to make progress against the major challenge of our time, multimorbid cardiometabolic disease. We are delighted that MRC have backed us with this programme.
- Professor David Ray
New research led by Professor David Ray, and involving scientists from the universities of Oxford, Aberdeen, Bristol and Manchester, aims to break this vicious cycle.
The five-year £2.6m MRC Programme Grant will enable the team to discover how changes to the body clock, or its alignment to the environment (e.g. shift work) and nutrition (e.g. altered patterns of daily eating) contribute to cardiometabolic disease.
Pilot work has already identified promising new targets and genes to study, using the following approaches:
Analysing existing big data
The team will analyse existing genetic and other health-related data from millions of people, available from research studies in humans carried out over the years. They will use sophisticated genetic techniques to find the genes and processes that link the body clock and health outcomes.
Developing animal and pre-clinical models
The team will study mice in which they can manipulate the body clock and alter the environment (e.g. light dark cycle) and diet to model the changes seen in people. They will determine how these changes affect processes involved in cardiometabolic disease.
Researchers will test these new discoveries using both pre-clinical and animal models. These models enable the researchers to delete the gene and see how this affects cardiometabolic disease and the underlying disease mechanisms.
Studying human volunteers
The research will benefit from a valuable resource of human volunteers who have agreed to be involved.
A significant number of people in this group have natural variations in a particular gene that the researchers are already interested in. They have shown that this gene links SCRD, cardiometabolic disease, and alteration in a specific family of lipids, the sphingomyelins, which include a potentially harmful group of lipids known as ceramides. The team will study these volunteers in detail to see how this genetic variation affects their health.
Involving people living with SCRD and cardiometabolic disease
The research will involve people living with cardiometabolic disease, and those who are living with sleep and body clock issues (including shift workers).
This two-way communication between researchers and people living with the health conditions being studied ensures an understanding of the impact of the problems on people's lives. It sheds light on the steps people can take to protect themselves, what works, and what does not.
Testing interventions
The researchers will be able to test interventions that may be effective in slowing or reversing progressing to disease, which may ultimately help people already living with cardiometabolic disease.
The work will be integrated with initiatives to improve the measurement of sleep and rhythmic human activity using wearable devices. This will help identify novel risk biomarkers, and contribute to the moves to prevent the development of Type-2 Diabetes using targeted lifestyle interventions.
This ambitious five-year programme will transform our understanding of how sleep and the body clock affect cardiometabolic disease. It will enable new ways to measure this burden, mitigate the risk, and treat the consequences, improving people's health and wellbeing. The research will also lead to new insights into why cardiometabolic disease is so common and rising in scale with time.