Unravelling the effects of ageing on the type I interferon anti-viral response (360G-Wellcome-227946_Z_23_Z)

The resilience of the anti-viral immune system declines with age, yet there is significant heterogeneity in anti-viral immunity in older adults, resulting in diverse viral infection outcomes in this age group. Activation of type I interferon (IFN-I) responses are a fundamental component of innate anti-viral immunity, key for activation of early, direct anti-viral protection and later adaptive anti-viral immune responses. My preliminary data shows that IFN-I responses are compromised in older adults and I propose to use longitudinal investigations in key ageing studies to understand the spectrum of ageing IFN-I responses, particularly the relationship between IFN-I responses and rates of biological ageing, and how this is related to health during ageing. I will also examine how lifecourse history, including prior viral exposure, sculpts the ageing IFN-I response. I will explore the activation and regulation of IFN-I signalling during ageing and investigate mechanisms driving alterations of this important anti-viral response in older adults. This will be a multi-disciplinary endeavour, innovative in its application of cutting-edge approaches from two major fields of research - immunology and ageing - in unique longitudinal ageing studies.