TY  - JOUR
SP  - 1741
KW  - Leucocyte telomere length; Frailty; Biological age; UK biobank
IS  - 3
AV  - public
JF  - Journal of cachexia, sarcopenia and muscle
TI  - Association of shorter leucocyte telomere length with risk of frailty
Y1  - 2022/06//
N1  - © 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
PB  - Wiley-Blackwell
ID  - discovery10143617
A1  - Bountziouka, Vasiliki
A1  - Nelson, Christopher
A1  - Codd, Veryan
A1  - Wang, Qingning
A1  - Musicha, Crispin
A1  - Allara, Elias
A1  - Kaptoge, Stephen
A1  - Di Angelantonio, Emanuele
A1  - Butterworth, Adam
A1  - Thompson, John
A1  - Curtis, Elizabeth
A1  - Wood, Angela
A1  - Danesh, John
A1  - Harvey, Nicholas
A1  - Cooper, Cyrus
A1  - Samani, Nilesh
UR  - https://doi.org/10.1002/jcsm.12971
VL  - 13
N2  - 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 × 10?33), more likely to be female (61%, P = 1.97 × 10?129), and had shorter LTL (?0.13SD vs. 0.03SD, P = 5.43 × 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 × 10?12; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 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.
EP  - 1751
ER  -