Neutrophil function in healthy ageing, inflammation and frailty

  • Research type

    Research Study

  • Full title

    Neutrophil function in healthy ageing, inflammation and frailty

  • IRAS ID

    298365

  • Contact name

    Helen L Wright

  • Contact email

    hlwright@liverpool.ac.uk

  • Sponsor organisation

    University of Liverpool

  • Duration of Study in the UK

    3 years, 11 months, 30 days

  • Research summary

    Frailty is a common consequence of ageing and is defined as a group of older people who are at highest risk of adverse outcomes such as falls, disability, admission to hospital, or the need for long-term care. Frailty is often associated with poor mobility, muscle weakness, memory problems and poor eyesight and/or hearing. Changes to the immune system are also commonly associated with ageing and frailty; these include a decline in immune function leading to increased risk of infections and inflammageing, a state of chronic inflammation. Inflammageing is often associated with increased levels of circulating cytokines, including TNF and interleukins (ILs) such as IL-6, as well as raised systemic markers of inflammation such as CRP. Neutrophils are innate immune cells involved in host defense against particulate pathogens such as bacteria and fungi. During infection, neutrophils migrate from peripheral blood to sites of infection to initiate phagocytosis and bacterial killing, or production of neutrophil extracellular traps (NETs). Unwanted or unresolved neutrophil activation during inflammation can induce damage to host tissue via the release of ROS and proteases, and release of NETs may induce auto-immunity causing age-related inflammatory diseases such as rheumatoid arthritis. Several studies have identified a dysregulation of neutrophil function in older adults. For example, older neutrophils have a lower bacterial killing capacity and are less efficient at migration from the blood to sites of infection and cause damage to local tissues in the process. There is also evidence from animal studies that normal neutrophil function such as NET production may be impaired in older individuals. The reasons for the decline in immune function, and whether this is irreversible or could be therapeutically treated, are not yet understood and will be addressed in this 4-year project.

  • REC name

    South West - Central Bristol Research Ethics Committee

  • REC reference

    21/SW/0093

  • Date of REC Opinion

    20 Jul 2021

  • REC opinion

    Further Information Favourable Opinion