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Association of shorter leucocyte telomere length with risk of frailty

Association of shorter leucocyte telomere length with risk of frailty
Association of shorter leucocyte telomere length with risk 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 × 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.

Biological age, Frailty, Leucocyte telomere length, UK biobank
2190-5991
1741-1751
Bountziouka, Vasiliki
e27d3872-eacd-461c-a70f-31d69a833b14
Nelson, Christopher P.
7354f6bf-5b2a-4670-a234-4bdd5cf8dcd6
Codd, Veryan
18ed4108-1eb4-4702-bff1-468efae23aae
Wang, Qingning
f65fb117-c5fb-4c02-8bfa-8d1769854038
Musicha, Crispin
28597971-7c73-4f28-9b3c-afaa3951f100
Allara, Elias
6da74d5d-2cb7-4a2d-a483-2a77593fa9d2
Kaptoge, Stephen K.
6dcecd22-dd25-4a8b-9dc2-54c781ff8394
Di Angelantonio, Emanuele
32a4e2e1-72e5-4ee9-93f2-bd78b4a53867
Butterworth, Adam S.
41de379c-9caa-495d-9009-33feab4bdbb0
Thompson, John R.
12f974cd-7581-469c-8e0f-717bdb4663e6
Curtis, Elizabeth
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Wood, Angela M.
0843764d-4605-495f-9047-7af14f435d96
Danesh, John N.
d00651c2-10c4-4ff6-ad32-cc2d7e0c2783
Harvey, Nicholas
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Cooper, Cyrus
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Samani, Nilesh J.
548b29ab-a422-4827-a9c6-5db0e6cf8ae6
Bountziouka, Vasiliki
e27d3872-eacd-461c-a70f-31d69a833b14
Nelson, Christopher P.
7354f6bf-5b2a-4670-a234-4bdd5cf8dcd6
Codd, Veryan
18ed4108-1eb4-4702-bff1-468efae23aae
Wang, Qingning
f65fb117-c5fb-4c02-8bfa-8d1769854038
Musicha, Crispin
28597971-7c73-4f28-9b3c-afaa3951f100
Allara, Elias
6da74d5d-2cb7-4a2d-a483-2a77593fa9d2
Kaptoge, Stephen K.
6dcecd22-dd25-4a8b-9dc2-54c781ff8394
Di Angelantonio, Emanuele
32a4e2e1-72e5-4ee9-93f2-bd78b4a53867
Butterworth, Adam S.
41de379c-9caa-495d-9009-33feab4bdbb0
Thompson, John R.
12f974cd-7581-469c-8e0f-717bdb4663e6
Curtis, Elizabeth
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Wood, Angela M.
0843764d-4605-495f-9047-7af14f435d96
Danesh, John N.
d00651c2-10c4-4ff6-ad32-cc2d7e0c2783
Harvey, Nicholas
ce487fb4-d360-4aac-9d17-9466d6cba145
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Samani, Nilesh J.
548b29ab-a422-4827-a9c6-5db0e6cf8ae6

Bountziouka, Vasiliki, Nelson, Christopher P., Codd, Veryan, Wang, Qingning, Musicha, Crispin, Allara, Elias, Kaptoge, Stephen K., Di Angelantonio, Emanuele, Butterworth, Adam S., Thompson, John R., Curtis, Elizabeth, Wood, Angela M., Danesh, John N., Harvey, Nicholas, Cooper, Cyrus and Samani, Nilesh J. (2022) Association of shorter leucocyte telomere length with risk of frailty. Journal of Cachexia, Sarcopenia and Muscle, 13 (1), 1741-1751. (doi:10.1002/jcsm.12971).

Record type: Article

Abstract

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.

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Accepted/In Press date: 15 February 2022
Published date: June 2022
Additional Information: © 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.
Keywords: Biological age, Frailty, Leucocyte telomere length, UK biobank

Identifiers

Local EPrints ID: 455160
URI: http://eprints.soton.ac.uk/id/eprint/455160
ISSN: 2190-5991
PURE UUID: 3c0f11ff-dcbe-494a-8483-fefa8f7d2e41
ORCID for Elizabeth Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709

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Date deposited: 10 Mar 2022 20:15
Last modified: 15 Nov 2022 02:48

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Contributors

Author: Vasiliki Bountziouka
Author: Christopher P. Nelson
Author: Veryan Codd
Author: Qingning Wang
Author: Crispin Musicha
Author: Elias Allara
Author: Stephen K. Kaptoge
Author: Emanuele Di Angelantonio
Author: Adam S. Butterworth
Author: John R. Thompson
Author: Angela M. Wood
Author: John N. Danesh
Author: Nicholas Harvey ORCID iD
Author: Cyrus Cooper ORCID iD
Author: Nilesh J. Samani

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