Extracellular matrix downregulation in the Drosophila heart preserves contractile function and improves lifespan

Ayla O. Sessions, Gaurav Kaushik, Sarah Parker, Koen Raedschelders, Rolf Bodmer, Jennifer E. Van Eyk, Adam J. Engler

Research output: Contribution to journalArticlepeer-review

Abstract

Aging is associated with extensive remodeling of the heart, including basement membrane (BM) components that surround cardiomyocytes. Remodeling is thought to impair cardiac mechanotransduction, but the contribution of specific BM components to age-related lateral communication between cardiomyocytes is unclear. Using a genetically tractable, rapidly aging model with sufficient cardiac genetic homology and morphology, e.g. Drosophila melanogaster, we observed differential regulation of BM collagens between laboratory strains, correlating with changes in muscle physiology leading to cardiac dysfunction. Therefore, we sought to understand the extent to which BM proteins modulate contractile function during aging. Cardiac-restricted knockdown of ECM genes Pericardin, Laminin A, and Viking in Drosophila prevented age-associated heart tube restriction and increased contractility, even under viscous load. Most notably, reduction of Laminin A expression correlated with an overall preservation of contractile velocity with age and extension of organismal lifespan. Global heterozygous knockdown confirmed these data, which provides new evidence of a direct link between BM homeostasis, contractility, and maintenance of lifespan.

Original languageEnglish (US)
Pages (from-to)15-27
Number of pages13
JournalMatrix Biology
Volume62
DOIs
StatePublished - Oct 2017

Keywords

  • Aging
  • Basement membrane
  • Drosophila
  • Extracellular matrix
  • Laminin A

ASJC Scopus subject areas

  • Molecular Biology

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