Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: Cross-sectional findings from the Newcastle 85+ Study (2012)

Author(s): Collerton J, Martin-Ruiz C, Davies K, Hilkens CM, Isaacs J, Kolenda C, Parker C, Dunn M, Catt M, Jagger C, von Zglinicki T, Kirkwood TB

    Abstract: Age-related frailty is an increasing societal challenge with growing emphasis on identifying its underlying pathophysiology and prospects for intervention. We report findings from the first comprehensive study of frailty and biomarkers of inflammation, immunosenescence and cellular ageing in the very old. Using cross-sectional data from the Newcastle 85+ Study (n=845, aged 85), frailty was operationalized by the Fried and Rockwood models and biomarker associations explored using regression analysis. We confirmed the importance of inflammatory markers (IL-6, TNF-alpha, CRP, neutrophils) in frailty in the very old, previously established only in younger-old populations. Limited evidence was found for immunosenescence in frailty; although total lymphocyte count was inversely related, no association was found with the immune risk profile and the inverse associations observed with memory/naive CD8 T and B cell ratios were in the opposite direction to that expected. We found no association with frailty in the very old for CMV sero-positivity, telomere length, markers of oxidative stress or DNA damage and repair. The Fried and Rockwood frailty models measure different albeit overlapping concepts yet biomarker associations were generally consistent between models. Difficulties in operationalizing the Fried model, due to high levels of co-morbidity, limit its utility in the very old.

    Notes: Collerton, Joanna Martin-Ruiz, Carmen Davies, Karen Hilkens, Catharien M Isaacs, John Kolenda, Claire Parker, Craig Dunn, Michael Catt, Michael Jagger, Carol von Zglinicki, Thomas Kirkwood, Thomas B L Ireland Mech Ageing Dev. 2012 Jun;133(6):456-66. Epub 2012 Jun 1.

    • Alternate Journal: Mechanisms of ageing and development
    • Date: 01-06-2012
    • Journal: Mechanisms of Ageing and Development
    • Volume: 133
    • Issue: 6
    • Pages: 456-466
    • Publisher: Elsevier Ireland Ltd
    • Publication type: Article
    • Bibliographic status: Published

    Dr Catharien Hilkens
    Reader in Immunotherapy

    Professor Carol Jagger
    AXA Prof of Epidemiology of Ageing