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

Lookup NU author(s): Dr Joanna Collerton, Dr Carmen Martin-RuizORCiD, karen Davies, Professor Catharien Hilkens, Professor John IsaacsORCiD, Claire Kolenda, Dr Craig Parker, Dr Michael Dunn, Professor Mike Catt, Emerita Professor Carol Jagger, Professor Thomas von Zglinicki, Emeritus Professor Thomas Kirkwood

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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.


Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Mechanisms of Ageing and Development

Year: 2012

Volume: 133

Issue: 6

Pages: 456-466

Print publication date: 01/06/2012

ISSN (print): 0047-6374

ISSN (electronic): 1872-6216

Publisher: Elsevier Ireland Ltd

URL: http://dx.doi.org/10.1016/j.mad.2012.05.005

DOI: 10.1016/j.mad.2012.05.005

PubMed id: 22663935

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.


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Funding

Funder referenceFunder name
UK Medical Research Council
G0500997Biotechnology and UK Biological Sciences Research Council
G0601333Unilever Discover Colworth

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