title: Expression patterns of cardiac aging in Drosophila.
abstract: Aging causes cardiac dysfunction, often leading to heart failure and death. The molecular basis of age-associated changes in cardiac structure and function is largely unknown. The fruit fly, Drosophila melanogaster, is well-suited to investigate the genetics of cardiac aging. Flies age rapidly over the course of weeks, benefit from many tools to easily manipulate their genome, and their heart has significant genetic and phenotypic similarities to the human heart. Here, we performed a cardiac-specific gene expression study on aging Drosophila and carried out a comparative meta-analysis with published rodent data. Pathway level transcriptome comparisons suggest that age-related, extra-cellular matrix remodeling and alterations in mitochondrial metabolism, protein handling, and contractile functions are conserved between Drosophila and rodent hearts. However, expression of only a few individual genes similarly changed over time between and even within species. We also examined gene expression in single fly hearts and found significant variability as has been reported in rodents. We propose that individuals may arrive at similar cardiac aging phenotypes via dissimilar transcriptional changes, including those in transcription factors and micro-RNAs. Finally, our data suggest the transcription factor Odd-skipped, which is essential for normal heart development, is also a crucial regulator of cardiac aging.
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Cannon
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.|Department of Biopharmaceutical Sciences, Keck Graduate Institute, Claremont, CA, USA.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Zambon
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Cammarato
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Georg
authors.initials: G
authors.lastname: Vogler
authors.affiliation: Department of Biopharmaceutical Sciences, Keck Graduate Institute, Claremont, CA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Munoz
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Taylor
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cartry
authors.affiliation: Department of Biology, Molecular Biology Institute, and The Heart Institute, San Diego State University, San Diego, CA, USA.
authors.forename: Sanford I
authors.initials: SI
authors.lastname: Bernstein
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.affiliation: Development, Aging and Regeneration Program, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
authors.forename: Rolf
authors.initials: R
authors.lastname: Bodmer
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D019295:Computational Biology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D063990:Gene Ontology; D017344:Genes, Insect; D008322:Mammals / Q000235:genetics; D044085:Microfluidics; D009206:Myocardium / Q000378:metabolism*; D036103:Nanotechnology; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors
keywords: LysX; MMP1; Odd-skipped; arrhythmia; cardiomyopathy; heart; nanofluidics; senescence