Age-dependent Lamin changes induce cardiac dysfunction via dysregulation of cardiac transcriptional programs.

ABSTRACT: As we age, structural changes contribute to progressive decline in organ function, which in the heart act through poorly characterized mechanisms. Taking advantage of the short lifespan and conserved cardiac proteome of the fruit fly, we found that cardiomyocytes exhibit progressive loss of Lamin C (mammalian Lamin A/C homologue) with age, coincident with decreasing nuclear size and increasing nuclear stiffness. Premature genetic reduction of Lamin C phenocopies aging's effects on the nucleus, and subsequently decreases heart contractility and sarcomere organization. Surprisingly, Lamin C reduction downregulates myogenic transcription factors and cytoskeletal regulators, possibly via reduced chromatin accessibility. Subsequently, we find a role for cardiac transcription factors in regulati

SUBMITTER: Kirkland NJ 

PROVIDER: S-EPMC9956937 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature