Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study.
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/naïve 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.
Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom. joanna.collerton@ncl.ac.uk
Joanna
J
Collerton
Carmen
C
Martin-Ruiz
Karen
K
Davies
Catharien M
CM
Hilkens
John
J
Isaacs
Claire
C
Kolenda
Craig
C
Parker
Michael
M
Dunn
Michael
M
Catt
Carol
C
Jagger
Thomas
T
von Zglinicki
Thomas B L
TB
Kirkwood
D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016516:CD4-CD8 Ratio; D016922:Cellular Senescence / Q000276:immunology*; D003430:Cross-Sectional Studies; D003586:Cytomegalovirus Infections / Q000097:blood / Q000276:immunology; D004249:DNA Damage; D004260:DNA Repair; D004739:England / Q000453:epidemiology; D005260:Female; D016330:Frail Elderly / Q000706:statistics & numerical data*; D006801:Humans; D007249:Inflammation / Q000453:epidemiology* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology; D008297:Male; D018384:Oxidative Stress; D015995:Prevalence; D059505:Telomere Homeostasis
D015415:Biomarkers; D018836:Inflammation Mediators