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

Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, United Kingdom.
Mechanisms of ageing and development (Impact Factor: 4.18). 06/2012; 133(6):456-66. DOI: 10.1016/j.mad.2012.05.005
Source: PubMed

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/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.

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    ABSTRACT: Background Older adults are at an increased risk of death, but not all people of the same age have the same risk. Many methods identify frail people (that is, those at increased risk) but these often require time-consuming interactions with health care providers. We evaluated whether standard laboratory tests on their own, or added to a clinical frailty index (FI), could improve identification of older adults at increased risk of death.Methods This is a secondary analysis of a prospective cohort study, where community dwelling and institutionalized participants in the Canadian Study of Health and Aging who also volunteered for blood collection (n¿=¿1,013) were followed for up to six years. A standard FI (FI-CSHA) was constructed from data obtained during the clinical evaluation and a second, novel FI was constructed from laboratory data plus systolic and diastolic blood pressure measurements (FI-LAB). A combined FI included all items from each index. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves.ResultsOf 1,013 participants, 51.3% had died by six years. The mean baseline value of the FI-LAB was 0.27 (standard deviation 0.11; range 0.05 to 0.63), the FI-CSHA was 0.25 (0.11; 0.02 to 0.72), and the combined FI was 0.26 (0.09; 0.06 to 0.59). In an age- and sex-adjusted model, with each increment in the FI-LAB, the hazard ratios increased by 2.8% (95% confidence interval 1.02 to 1.04). The hazard ratios for the FI-CSHA and the combined FI were 1.02 (1.01 to 1.03) and 1.04 (1.03 to 1.05), respectively. The FI-LAB and FI-CSHA remained independently associated with death in the face of the other. The areas under the ROC curves were 0.72 for FI-LAB, 0.73 for FI-CSHA and 0.74 for the combined FI.Conclusions An FI based on routine laboratory data can identify older adults at increased risk of death. Additional evaluation of this approach in clinical settings is warranted.
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    PLoS ONE 10/2014; 9(10):e108481. · 3.53 Impact Factor
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    ABSTRACT: Background. Telomere shortening in peripheral blood mononuclear cells (PBMCs) has been associated with biological age and several chronic degenerative diseases. However, the relationship between telomere length and sarcopenia, a hallmark of the aging process, is unknown. The aim of the present study was therefore to determine whether PBMC telomeres obtained from sarcopenic older persons were shorter relative to non-sarcopenic peers. We further explored if PBMC telomere length was associated with frailty, a major clinical correlate of sarcopenia. Methods. Analyses were conducted in 142 persons aged >/= 65 years referred to a geriatric outpatient clinic (University Hospital). The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People criteria, with bioelectrical impedance analysis used for muscle mass estimation. The frailty status was determined by both the Fried’s criteria (physical frailty, PF) and a modified Rockwood’s frailty index (FI). Telomere length was measured in PBMCs by quantitative real-time polymerase chain reaction according to the Telomere/Single copy gene ratio (T/S) method. Results. Among 142 outpatients (mean age 75.0 ± 6.5 years, 59.2% women), sarcopenia was diagnosed in 23 individuals (19.3%). The PF phenotype was detected in 74 participants (52.1%). The average FI score was 0.46 ± 0.17. PBMC telomeres were shorter in sarcopenic subjects (T/S = 0.21; 95% CI: 0.18 – 0.24) relative to non-sarcopenic individuals (T/S = 0.26; 95%: CI: 0.24 – 0.28; p = 0.01), independent of age, gender, smoking habit, or comorbidity. No significant associations were determined between telomere length and either PF or FI. Conclusion. PBMC telomere length, expressed as T/S values, is shorter in older outpatients with sarcopenia. The cross-sectional assessment of PBMC telomere length is not sufficient at capturing the complex, multidimensional syndrome of frailty.
    Frontiers in Aging Neuroscience 08/2014; 6(233). · 2.84 Impact Factor

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