期刊
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
卷 13, 期 3, 页码 1741-1751出版社
WILEY
DOI: 10.1002/jcsm.12971
关键词
Leucocyte telomere length; Frailty; Biological age; UK biobank
资金
- National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre [BRC-1215-20010]
- BHF [SP/16/4/32697, RG/13/13/30194, RG/18/13/33946]
- Health Data Research UK
- NIHR Cambridge Biomedical Research Centre [BRC-1215-20014]
- NIHR Blood and Transplant Research Unit in Donor Health and Genomics [NIHR BTRU-2014-10024]
- MRC [MR/L003120/1]
- EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart [11607]
- Medical Research Council (MRC) [4050502589]
- National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton
- University Hospital Southampton NHS Foundation Trust
- NIHR Oxford Biomedical Research Centre, University of Oxford
- NIHR Senior Investigator Award
This study utilized cross-sectional data from the UK Biobank and found an association between leucocyte telomere length (LTL) and the risk of frailty, independent of age and other risk factors. This suggests that LTL may be an additional biological determinant of frailty.
Background Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty. Methods We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal. Results Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 x 10(-33)), more likely to be female (61%, P = 1.97 x 10(-129)), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 x 10(-111)) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 x 10(-12); 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 x 10(-30)). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13). Conclusions Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.
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