The Present and Future
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Telomere Length as Cardiovascular Aging Biomarker: JACC Review Topic of the Week

https://doi.org/10.1016/j.jacc.2018.06.014Get rights and content
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Abstract

Telomeres shorten with age, the major risk factor for atherosclerotic cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD patients thus suggested that critical telomere shortening may contribute to premature biological aging and aCVD. Therefore, telomere length often is suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian randomization studies; however, epidemiological research has shown disappointingly low effect sizes. It therefore remains uncertain whether telomere shortening is a cause of aCVD or merely a consequence. The authors argue that elucidating the mechanistic foundation of these findings is essential for any possible translation of telomere biology to the clinic. Here, they critically evaluate evidence for causality in animal models and human studies, and review popular hypotheses and discuss their clinical implications. The authors identify 4 key questions that any successful mechanistic theory should address, and they discuss how atherosclerosis-associated local telomere attrition may provide the answers.

Key Words

atherosclerosis
biological aging
epidemiology
telomerase

Abbreviations and Acronyms

aCVD
atherosclerotic cardiovascular disease
DKC
dyskeratosis congenita
GWAS
genome-wide association study
qPCR
quantitative polymerase chain reaction
SNP
single nucleotide polymorphism
TERC
telomerase RNA component
TERT
telomerase reverse transcriptase
TL
telomere length

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Funding provided by the Spanish Ministerio de Economía, Industria y Competitividad and the Pro-CNIC Foundation, and a Severo Ochoa Center of Excellence (award SEV-2015-0505) in support of CNIC. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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