Understanding and manipulating our
immune system to protect against ageing
Ageing is the most important non-modifiable risk factor for a number of diseases and conditions of the immune system including ischaemia reperfusion injury (e.g. myocardial infarction and stroke), cancer, infections, wound healing, degenerative diseases (e.g. vascular dementia, Alzheimer’s disease) and cardiovascular diseases. Ageing is also associated with several morbidities that finally lead to organ failure and death.
Multimorbidity (i.e. two or more long-term health conditions) is prevalent as we age, with 75% of adults by the age of 70 having multimorbidities. These effects increase the risk of infections in the elderly and are at greater risk for infections (e.g. COVID-19), with worse outcomes. Additionally, inflammaging affects immune responses to illness, infections and vaccines, which may lead vaccination against e.g. SARS-CoV-2 being less effective, or not lasting as long as in younger patient cohorts. How inflammageing affects COVID-19 risk and poor outcome in the elderly remains unknown and is of great unmet clinical need to help identify potential novel disease biomarkers for future clinical trials.
In summary, we are particularly interested in the mode, dynamics and mechanisms of inflammaging that occur in the microcirculation (both in the brain and systemic organs). The aim of this project is to provide a greater understanding of the complex haemodynamic responses of the immune system as we age in order to drive drug discovery programmes aimed at manipulating our immune system to protect against ageing and help solutions to key global challenges.
As we age, our immune system undergoes a dynamic change characterised by low-grade chronic inflammation and involving a number of immune cells (e.g. neutrophils, platelets and endothelial cells) and pro-inflammatory cytokines e.g. tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. This chronic activation of inflammation associated with ageing has been termed ‘inflammageing’ and although the detrimental effects of ageing are well defined, mechanisms contributing to poor outcomes following many morbidities remain unknown. In addition, these effects may also be compounded by additional co-morbidities including environmental factors (e.g. stressful environments, alcohol consumption, smoking).