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

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

doi:10.1007/s13167-024-00355-7

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

EPMA J. 2024 Feb 15;15(1):99-110. doi: 10.1007/s13167-024-00355-7. eCollection 2024 Mar.

Authors

Xuening Jian¹, Wenxin Sun¹, Jie Zhang¹, Qiaoyun Zhang², Xiaoni Meng¹, Huimin Lu¹, Deqiang Zheng¹, Lijuan Wu¹, Youxin Wang^{1

3

4}

Affiliations

¹ School of Public Health, Capital Medical University, Beijing, 100069 China.
² Department of Anaesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
³ School of Public Health, North China University of Science and Technology, Tangshan, 063210 China.
⁴ Beijing Key Laboratory of Clinical Epidemiology, Capital Medical University, Beijing, 100069 China.

PMID: 38463625
PMCID: PMC10923753 (available on 2025-03-01)
DOI: 10.1007/s13167-024-00355-7

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.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-024-00355-7.

Keywords: All-cause mortality; Cancer-specific mortality; Cardiovascular-specific mortality; Frailty; Leucocyte telomere length; Predictive preventive personalized medicine (PPPM / 3PM).

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