Association of Telomere Length With Risk of Disease and Mortality

Abstract

IMPORTANCE Telomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders. OBJECTIVE To determine the association between LTL and overall as well as disease-specific mortality and morbidity. DESIGN, SETTING, AND PARTICIPANTS This multicenter, community-based cohort study conducted from March 2006 to December 2010 included longitudinal follow-up (mean [SD], 12 [2] years) for 472 432 English participants from the United Kingdom Biobank (UK Biobank) and analyzed morbidity and mortality. The data were analyzed in 2021.MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) and odds ratios for mortality and morbidity associated with a standard deviation change in LTL, adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and ethnicity. RESULTSThis study included a total of 472 432 English participants, of whom 54% were women (mean age, 57 years). Reduced LTL was associated with increased overall (HR,

Study of the associations between short telomeres, sex hormones and pulmonary fibrosis

“…Building on previously reported findings for multiple other diseases in both sexes together 42,43 , IPF prevalence showed strong associations with LTL for both males (OR=0.63, P=2.2×10 −38 ) and females (OR=0.69, P=8.9×10 −16 ), with odds ratios much lower than those for other reported associated comorbidities of IPF such as coronary artery disease and type II diabetes (Figure 1, Supplement:S1). A similar, slightly weaker association was also found for a broader clinical definition of interstitial lung disease (ILD).…”

“…Although overt TERT expression is insufficient to cause malignant transformation, its presence can promote unchecked proliferation; over-expression of telomerase is detected in around 90% of human cancers 15 . Shorter telomeres are generally associated with mortality 42,43 , yet we found this to be the case for men only (Figure 2), probably because a higher proportion of female deaths are caused by cancer, which is associated with longer telomeres (in UKBB, 68% of deaths amongst the top 20 causes for females were cancer-related whereas for males, this figure was 47% 59 ).…”

Carcinogenesis induced by space radiation: A systematic review

“…Many epigenetic and gene expression changes were detected during Scott Kelly's year-long mission, but most of them returned to normal upon return to Earth [48] . Altered telomere length is linked to age-related pathologies, including dementia, cardiovascular disease, and cancer [49] . The NASA Twins Study showed astronauts suffered DNA damage and telomere length dynamics after long space missions.…”

Ann Robinson’s research reviews—27 January 2022

“…Leucocyte telomere length (LTL) is a biomarker for cell damage and can be seen as a mitotic clock, ticking away as we age. A cohort study using UK Biobank data from more than 450 000 people, and with a follow-up of over five million person-years, found that shorter baseline LTL was associated with a small increased mortality rate overall and an increase in some disease-specific mortalities such as deaths from cardiovascular and respiratory disease 1. It’s complicated, however: shorter LTL wasn’t associated with an increase in total cancer-related deaths, although some cancers such as myeloid and oesophageal cancers were more prevalent.…”