Accelerated ageing as cause of disease pathogenesis, progression and multi-morbidity in Chronic Obstructive Pulmonary Disease (360G-Wellcome-203823_Z_16_A)

Ageing is linked with defects in the immune system which contribute to many chronic inflammatory conditions. Chronic obstructive pulmonary disease (COPD) is a common, debilitating lung disease with limited treatment options and no known cure. It is the third leading cause of death globally, costing the UK £1B annually in disability. The causes of COPD are poorly understood, affecting smokers and non-smokers alike. Our data shows that immune cells (leukocytes) in patients with COPD make abnormal and injurious responses which damage the lung but also effect other organs in the body. As cells age they are removed and replaced with new functioning cells. Failure to remove these "senescent" cells is linked with age-related illnesses including diabetes and heart disease. Such conditions are common in patients with COPD. We hypothesize that damaging immune responses in COPD are caused by the accumulation of senescent leukocytes. We will examine the characteristics of blood leukocytes and test their ability to move into and within tissue. We will also determine the importance of specific regulatory pathways linked to leukocyte functions. Comparisons will be made between patients with COPD, cardiovascular disease or diabetes to test whether leukocyte senescence is a causative link for age-related inflammatory diseases.