Inflammageing: Delineating the role of type I IFNs in the regulation of senescence and associated inflammatory responses

Systemic inflammation is often increased as people age (inflammageing). Although increased inflammation is strongly linked to age related disease pathology, it is still unclear how this inflammageing is driven and regulated. Recently, increased DNA damage due to cellular ageing has been implicated in driving inflammation and/or cellular senescence, which can result in compromised immunity. Type I interferon (IFNs) are a family of cytokines that are critical in regulating many aspects of immunity. They are produced early in immune responses by many of the same pathways that regulate production of pro-inflammatory cytokines. Indeed, DNA can be a potent inducer of type I IFN expression. Recent studies suggest type I IFNs can regulate inflammation in senescence; however, the mechanisms behind this are unknown and not assessed in human age-related diseases. This project aims to determine the impact of type I IFNs in regulating inflammatory responses in ageing and senescence and how this is linked age related compromised immunity.