Telomere Length and All-Cause Mortality: A Meta-analysis.
Level 3 - non-randomized controlled study
Meta-analysis of prospective cohort studies (Level 3 evidence).
PubMed 30254001 · doi:10.1016/j.arr.2018.09.002
What was done
A meta-analysis was conducted combining unpublished data from four Swedish Twin Registry (STR) cohorts (12,083 individuals, 2,517 deaths) and 21 published cohort studies. The primary analysis examined the association between leukocyte telomere length (TL) and all-cause mortality across all 25 studies (totaling 121,749 individuals and 21,763 deaths), evaluating risk per one standard deviation (SD) decrement in TL and comparing the shortest versus longest TL quartile. Age-stratified analyses were also performed.
What was found
In the STR cohorts, each 1 SD decrement in leukocyte TL was associated with a 13% increase in all-cause mortality risk (95% CI: 7% to 19%), and individuals in the shortest TL quartile had a 44% higher hazard (95% CI: 27% to 63%) compared with the longest quartile. In the pooled meta-analysis of all 25 studies, a 1 SD TL decrement was associated with a hazard ratio of 1.09 (95% CI: 1.06 to 1.13), and the shortest quartile had a 26% higher hazard (95% CI: 15% to 38%) versus the longest quartile. Significant between-study heterogeneity was observed. Age-stratified analyses showed a smaller hazard ratio in individuals older than 80 years.
Why it matters
This large synthesis confirms that shorter leukocyte telomere length is modestly associated with higher all-cause mortality in the general population, though the predictive association diminishes in the oldest individuals.
Limits
The findings are derived from observational cohort designs, precluding causal inference. Substantial between-study heterogeneity was present, attributable in part to differences in TL measurement assays and participant age at sampling. Residual confounding across underlying cohorts cannot be ruled out from the reported data.
Cited by
- supports Shorter telomeres are associated with aging and potentially worse health outcomes.