Telomere shortening in laminopathic dilated cardiomyopathy.

Abstract

Laminopathies are a group of rare disease due to mutations in the LMNA gene, which is crucial for nuclear integrity and cellular rigidity. Depending on the mutation, the disease manifests in striated muscles, adipose tissues, nerves, and the heart. Although many laminopathic patients exhibit accelerated aging syndromes, the connection as to why loss of LMNA drives aging remains unknown. Herein, we present evidence that cardiomyocytes from laminopathic heart sections exhibit shortened telomeres. Patient derived hiPSC-CMs we observed LMNA mutation results in myocardial enlargement and altered contractility in cardiomyocytes. Further, laminopathic murine cardiomyocytes recapitulates telomere attrition phenotype.