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Frailty mediating the causality between leucocyte telomere length and mortality: a cohort study of 440,551 UK Biobank participants

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Abstract

Introduction

Previous studies reported leucocyte telomere length (LTL) and frailty were associated with mortality, but it remains unclear whether frailty serves as a mediator in the relationship between leucocyte telomere length and mortality risk. This study aimed to evaluate how measuring LTL and frailty can support early monitoring and prevention of risk of mortality from the prospective of predictive, preventive, and personalized medicine (PPPM/3PM).

Methods

We included 440,551 participants from the UK Biobank between the baseline visit (2006–2010) and November 30, 2022. The time-dependent Cox proportional hazards model was conducted to assess the association between LTL and frailty index with the risk of mortality. Furthermore, we conducted causal mediation analyses to examine the extent to which frailty mediated the association between LTL and mortality.

Results

During a median follow-up of 13.74 years, each SD increase in LTL significantly decreased the risk of all-cause [hazard ratio (HR): 0.94, 95% confidence interval (CI): 0.93–0.95] and CVD-specific mortality (HR: 0.92, 95% CI: 0.90–0.95). The SD increase in FI elevated the risk of all-cause (HR: 1.35, 95% CI: 1.34–1.36), CVD-specific (HR: 1.47, 95% CI: 1.44–1.50), and cancer-specific mortality (HR: 1.22, 95% CI: 1.20–1.24). Frailty mediated approximately 10% of the association between LTL and all-cause and CVD-specific mortality.

Conclusions

Our results indicate that frailty mediates the effect of LTL on all-cause and CVD-specific mortality. There findings might be valuable to predict, prevent, and reduce mortality through primary prevention and healthcare in context of PPPM.

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Availability of data and material

This research was conducted using the UK Biobank study under Application Number 95259. Data from UK Biobank are available on application at www.ukbiobank.ac.uk/register-apply.

Code availability

Data are available on reasonable request from the corresponding author.

Abbreviations

CI:

Confidence interval

CVD:

Cardiovascular diseases

FI:

Frailty index

FP:

Frailty phenotype

HR:

Hazard ratio

IQR:

Interquartile range

LTL:

Leucocyte telomere length

NDE:

Natural direct effect

NIE:

Natural indirect effect

PPPM/3PM:

Predictive, preventive, and personalized medicine

SD:

Standard deviation

TDI:

Townsend deprivation index

TE:

Total effect

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Funding

This work was supported by the National Key R&D Program of China-European Commission Horizon 2020 (2017YFE0118800-779238) and Beijing Talents Project (2020A17).

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Authors and Affiliations

  1. School of Public Health, Capital Medical University, Beijing, 100069, China

    Xuening Jian, Wenxin Sun, Jie Zhang, Xiaoni Meng, Huimin Lu, Deqiang Zheng, Lijuan Wu & Youxin Wang

  2. Department of Anaesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

    Qiaoyun Zhang

  3. School of Public Health, North China University of Science and Technology, Tangshan, 063210, China

    Youxin Wang

  4. Beijing Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, 100069, China

    Youxin Wang

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  1. Xuening Jian
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  8. Lijuan Wu
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Contributions

LW and YW contributed to the study conception and design. Analysis and interpretation of data was performed by XJ, WS, JZ, and HL. Drafting of the manuscript was performed by XJ, WS, QZ, and XM. YW did critical revision of the manuscript for important intellectual content. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lijuan Wu or Youxin Wang.

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Ethical approval of the UK Biobank was obtained from the National Health Service National Research Ethics Service, and all participants provided written informed consent.

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Jian, X., Sun, W., Zhang, J. et al. Frailty mediating the causality between leucocyte telomere length and mortality: a cohort study of 440,551 UK Biobank participants. EPMA Journal 15, 99–110 (2024). https://doi.org/10.1007/s13167-024-00355-7

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