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Cited by 36Frailty in Older AdultsTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

Association of shorter leucocyte telomere length with risk of frailty

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Bountziouka, Vasiliki, Nelson, Christopher P., Codd, Veryan, Wang, Qingning, Musicha, Crispin, Allara, Elias, Kaptoge, Stephen, Di Angelantonio, Emanuele +8 more·2022·Journal of Cachexia, Sarcopenia and Muscle
DOI 10.1002/jcsm.12971PMC PMC9178164

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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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  • In adults, shorter leukocyte telomere length is associated with a higher risk of frailty independently of chronological age and other established risk factors, but this does not establish that neonatal telomere length predicts later frailty.

    “In adults, shorter leukocyte TL has been associated with a higher risk of frailty independently of chronological age and other established risk factors [127], but this observation does not establish that neonatal TL predicts later frailty.”

    From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [127]

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Authors
Bountziouka, V., Nelson, C. P., Codd, V., Wang, Q., Musicha, C., Allara, E., Kaptoge, S., Di Angelantonio, E., Butterworth, A. S., Thompson, J. R., Curtis, E. M., Wood, A. M., Danesh, J. N., Harvey, N. C., Cooper, C., & Samani, N. J.
Affiliations
  • Department of Cardiovascular Sciences University of Leicester Leicester UK
  • University of Leicester (GB)
  • University of Cambridge (GB)
  • British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care University of Cambridge Cambridge UK
  • MRC Lifecourse Epidemiology Unit (GB)
  • University Hospital Southampton NHS Foundation Trust (GB)
Corresponding author
Samani, Nilesh J.
ORCID
Venue
Journal of Cachexia, Sarcopenia and Muscle
Publisher
Wiley
Published
2022-03-17
Volume
13
Issue
3
Pages
1741-1751
ISSN
  • 2190-5991 (ISSN-L)
  • 2190-6009
DOI
10.1002/jcsm.12971
PMC
PMC9178164
OpenAlex
W4220980680
Cited by
36
References
39
Citations by year
2026: 6 · 2025: 9 · 2024: 12 · 2023: 4 · 2022: 5
FWCI
4.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Cachexia Sarcopenia and Muscle (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
Medical Research Council (MR/M012816/1)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Keywords
frailty, leukocyte telomere length, biological age, telomere length, frailty risk factors, grip strength, walking speed, weight loss, physical activity, exhaustion, Mendelian randomization, causal inference, genetic variants, older adults, UK Biobank, multimorbidity, socioeconomic deprivation, sex differences in frailty
MeSH terms
Frailty, Adult, Cross-Sectional Studies, Female, Humans, Leukocytes, Male, Risk Factors, Telomere

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