The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly men

Abstract

Telomere length (TL) has been proposed as a marker of mitotic cell age and as a general index of human organismic aging. Short absolute leukocyte telomere length has been linked to cardiovascular-related morbidity and mortality. Our aim was to test whether the rate of change in leukocyte TL is related to mortality in a healthy elderly cohort. We examined a subsample of 236 randomly selected Caucasian participants from the MacArthur Health Aging Study (aged 70 to 79 years). DNA samples from baseline and 2.5 years later were assayed for mean TL of leukocytes. Percent change in TL was calculated as a measure of TL change (TLC). Associations between TL and TLC with 12-year overall and cardiovascular mortality were assessed. Over the 2.5 year period, 46% of the study participants showed maintenance of mean bulk TL, whereas 30% showed telomere shortening, and, unexpectedly, 24% showed telomere lengthening. For women, short baseline TL was related to greater mortality from cardiovascular disease (OR = 2.3; 95% CI: 1.0 - 5.3). For men, TLC (specifically shortening), but not baseline TL, was related to greater cardiovascular mortality, OR = 3.0 (95% CI: 1.1 - 8.2). This is the first demonstration that rate of telomere length change (TLC) predicts mortality and thus may be a useful prognostic factor for longevity.

Keywords: aging; cardiovascular disease; longevity; mortality; telomere length.

Figure 1.

Those with shorter (below median) telomere length at baseline (dashed line) had 2.3 times greater likelihood of mortality over the following 12 years compared to those with longer telomeres (solid line).

Figure 2.

Those with telomere shortening over a 2.5 year period (dashed line) had 3.0 times greater likelihood ofmortality over the 12 years since the baseline blood draw, compared to those without telomere shortening (solid line).