Association of shorter leucocyte telomere length with risk of frailty.

Adult Cross-Sectional Studies Female Frailty / epidemiology Humans Leukocytes Male Risk Factors Telomere / genetics
Biological age Frailty Leucocyte telomere length UK biobank

Journal

Journal of cachexia, sarcopenia and muscle
ISSN: 2190-6009
Titre abrégé: J Cachexia Sarcopenia Muscle
Pays: Germany
ID NLM: 101552883

Informations de publication

Date de publication:
06 2022
Historique:
revised: 24 01 2022
received: 20 09 2021
accepted: 15 02 2022
pubmed: 18 3 2022
medline: 11 6 2022
entrez: 17 3 2022
Statut: ppublish

Résumé

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. 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. Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10 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.

Sections du résumé

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
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.

Identifiants

DOI: 10.1002/jcsm.12971 PMID: 35297226 PMC: PMC9178164
pubmed: 35297226
doi: 10.1002/jcsm.12971
pmc: PMC9178164
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1741-1751

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : UK Medical Research Council (MRC)
ID : MR/M012816/1
Organisme : Medical Research Council
ID : MR/L003120/1
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_21022
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M012816/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Informations de copyright

© 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.

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Auteurs

Vasiliki Bountziouka (V)

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Christopher P Nelson (CP)

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Veryan Codd (V)

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Qingning Wang (Q)

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Crispin Musicha (C)

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

Elias Allara (E)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.

Stephen Kaptoge (S)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.

Emanuele Di Angelantonio (E)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.

Adam S Butterworth (AS)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.

John R Thompson (JR)

Department of Health Sciences, University of Leicester, Leicester, UK.

Elizabeth M Curtis (EM)

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

Angela M Wood (AM)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.

John N Danesh (JN)

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, Hinxton, UK.

Nicholas C Harvey (NC)

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.

Cyrus Cooper (C)

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.

Nilesh J Samani (NJ)

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.

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questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Association of shorter leucocyte telomere...
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questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fragilité › Association of shorter leucocyte telomere...
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