U-shaped relationship of leukocyte telomere length with all-cause and cancer-related mortality in older men

Yeap, Bu B, Hui, Jennie, Knuiman, Matthew W., Flicker, Leon, Divitini, Mark L., Arscott, Gillian M., Twigg, Stephen M., Almeida, Osvaldo P., Hankey, Graeme J., Golledge, Jonathan, Norman, Paul E., and Beilby, John P. (2021) U-shaped relationship of leukocyte telomere length with all-cause and cancer-related mortality in older men. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 76 (1). pp. 164-171.

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Background: Telomeres are essential DNA-protein complexes whose attrition results in cellular dysfunction and senescence. Leukocyte telomere length (LTL) correlates with tissue telomere length, representing a biomarker for biological age. However, its predictive value for mortality risk, and for cardiovascular versus cancer deaths, in older adults remains uncertain.

Method: We studied 3608 community-dwelling men aged 77.0 ± 3.6 years. Leukocyte telomere length was measured using multiplex quantitative PCR, expressed as amount of telomeric DNA relative to single-copy control gene (T/S ratio). Deaths from any cause, cardiovascular disease (CVD), and cancer were ascertained using data linkage. Curve fitting used restricted cubic splines and Cox regression analyses adjusted for age, cardiometabolic risk factors, and prevalent disease.

Results: There was a U-shaped association of LTL with all-cause mortality. Men with T/S ratio in the middle quartiles had lower mortality (quartiles, Q2 vs Q1, hazard ratio [HR] = 0.86, 95% confidence interval [CI] 0.77-0.97, p = .012; Q3 vs Q1 HR = 0.88, CI 0.79-0.99, p = .032). There was no association of LTL with CVD mortality. There was a U-shaped association of LTL with cancer mortality. Men with LTL in the middle quartiles had lower risk of cancer death (Q2 vs Q1, HR = 0.73, CI 0.59-0.90, p = .004; Q3 vs Q1, HR = 0.75, CI 0.61-0.92, p = .007).

Conclusions: In older men, both shorter and longer LTL are associated with all-cause mortality. A similar U-shaped association was seen with cancer deaths, with no association found for cardiovascular deaths. Further research is warranted to explore the prognostic utility of LTL in ageing.

Item ID: 67071
Item Type: Article (Research - C1)
ISSN: 1758-535X
Keywords: Cancer; Cardiovascular disease; Leukocyte telomere length; Male ageing; Mortality
Copyright Information: © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC 1060557, NHMRC 1117061, NHMRC 1155669
Date Deposited: 23 Jun 2021 23:19
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 50%
20 HEALTH > 2005 Specific population health (excl. Indigenous health) > 200504 Men's health @ 50%
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