Telomere Length: Implications for Atherogenesis

Abstract

Purpose of review: The purpose of the study is to explore the evidence linking telomere length with atherosclerotic ischemic disease.

Recent findings: There has been a recent expansion in strategies for measuring telomere length, including analyzing genome sequence data and capitalizing on genomic loci that associate with telomere length. These, together with more established approaches, have been used to generate a more complete picture of telomere length relationships with ischemic disease. Whereas earlier meta-analyses suggested an association between short leukocyte telomeres and ischemic disease, several recent large population studies now provide particularly compelling data, including an association with cardiovascular mortality. In addition, whether short leukocyte telomeres might be causally related to ischemic disease has been interrogated using Mendelian randomization strategies, which point to shorter leukocyte telomeres as a determining risk factor. Importantly however, the wide, interindividual variability in telomere length still means that a single assessment of leukocyte telomere length in an individual does not reliably report on a biological aging process. In this regard, recent multi-tissue analyses of telomere length dynamics are providing both new mechanistic insights into how telomere length and shortening rates may participate in atherogenesis and risk prediction opportunities. The balance of evidence indicates that short leukocyte telomeres confer a risk for atherosclerotic cardiovascular disease. Moreover, an integrated analysis of telomere lengths in leukocytes and other tissues may provide a window into individualized telomere dynamics, raising new prospects for risk management.

Keywords: Atherosclerosis; Coronary disease; Telomere length.

Fig. 1

Telomere length dynamics and atherosclerosis. There is wide genetically determined inter-individual variation in telomere length, reflected in the two birth telomeres depicted. Telomeres shorten during early development, when cell replication is high, and throughout adulthood depending on the replicative and oxidative stress burdens. Telomere shortening during early development is greatest in peripheral blood leukocytes, producing a telomere length gap with somatic tissue telomeres, including in skeletal and cardiac muscle (A). During adulthood, telomere attrition in skeletal muscle is similar to that in leukocytes but telomere length in cardiac atrial muscle is relatively stable over six decades (B). Short telomeres in adult circulating leukocytes, which will reflect relatively short telomeres in somatic tissues, are associated with and confer atherosclerosis risk (C). Insulin resistance is one proposed mediator. The patient-specific clinical value of a single leukocyte telomere length assessment remains to be determined. Individuals with wide muscle-leukocyte telomere length difference are predisposed to atherosclerotic disease (A), and the cardiac atrial muscle-leukocyte telomere gap may also capture stress accumulation and biological aging, with potential risk prediction value (B)