Short telomeres - A hallmark of heritable cardiomyopathies

Abstract

Cardiovascular diseases are the leading cause of death worldwide and the incidence increases with age. Genetic testing has taught us much about the pathogenic pathways that drive heritable cardiomyopathies. Here we discuss an unexpected link between shortened telomeres, a molecular marker of aging, and genetic cardiomyopathy. Positioned at the ends of chromosomes, telomeres are DNA repeats which serve as protective caps that shorten with each cell division in proliferative tissues. Cardiomyocytes are an anomaly, as they are largely non-proliferative post-birth and retain relatively stable telomere lengths throughout life in healthy individuals. However, there is mounting evidence that in disease states, cardiomyocyte telomeres significantly shorten. Moreover, this shortening may play an active role in the development of mitochondrial dysfunction central to the etiology of dilated and hypertrophic cardiomyopathies. Elucidation of the mechanisms that underlie the telomere-mitochondrial signaling axis in the heart will provide fresh insights into our understanding of genetic cardiomyopathies, and could lead to the identification of previously uncharacterized modes of therapeutic intervention.

Keywords: Cardiomyopathy; Mitochondria; TERT; TRF2; Telomerase; Telomere shortening.