As time flies by: Investigating cardiac aging in the short-lived Drosophila model

Blice-Baum, Anna C.; Guida, Maria Clara; Hartley, Paul S.; Adams, Peter D.; Bodmer, Rolf; Cammarato, Anthony

doi:10.1016/j.bbadis.2018.11.010

Cited by 25 publications

(21 citation statements)

References 251 publications

(434 reference statements)

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“…Besides the conservation of gene regulatory pathways, there is growing evidence that mutations in genes involved in cardiac diseases cause fly heart phenotypes similar to those observed clinically in humans [7]. Drosophila is used as a model organism for studying physiological, genetic, and epigenetic bases of cardiac aging [42]. There is also growing interest in using Drosophila to dissect molecular mechanisms of cardiac diseaseand aging-associated heart failure [43].…”

Section: Identifying Cardiac Aging Genes and Modeling Human Heart Diseases In Drosophilamentioning

confidence: 99%

“…In contrast, genes involved in ATP synthesis and β-oxidation, as well as in carbohydrate metabolism, were downregulated [46]. Among upregulated-with-age ECM genes are Matrix Metalloprotease 1 and 2 (Mmp1 and Mmp2), neprilysin 2 (Nep2), and TweedleF (TwdlF) [46], as well as cardiac collagen-IV (Viking) and pericardin (encoding a collagen IV-like protein) [42].…”

Section: Studying Cardiac Aging and Heart Failure In Drosophilamentioning

confidence: 99%

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Drosophila Heart as a Model for Cardiac Development and Diseases

Souidi

Jagla

2021

Cells

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The Drosophila heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal cells, migrate coordinately, and fuse to form the cardiac tube. Though much simpler, the fruit fly heart displays several developmental and functional similarities to the vertebrate heart and, as we discuss here, represents an attractive model system for dissecting mechanisms of cardiac aging and heart failure and identifying genes causing congenital heart diseases. Fast imaging technologies allow for the characterization of heartbeat parameters in the adult fly and there is growing evidence that cardiac dysfunction in human diseases could be reproduced and analyzed in Drosophila, as discussed here for heart defects associated with the myotonic dystrophy type 1. Overall, the power of genetics and unsuspected conservation of genes and pathways puts Drosophila at the heart of fundamental and applied cardiac research.

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Section: Identifying Cardiac Aging Genes and Modeling Human Heart Diseases In Drosophilamentioning

confidence: 99%

Section: Studying Cardiac Aging and Heart Failure In Drosophilamentioning

confidence: 99%

Drosophila Heart as a Model for Cardiac Development and Diseases

Souidi

Jagla

2021

Cells

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“…The flight ability and cardiac structure and function were also affected in a Drosophila model for HCM by expressing a mutation in human β-cardiac myosin heavy chain, known to cause HCM ( Kronert et al 2018 ). Several studies have shown that exercise training prevents age-related heart dysfunction in Drosophila ( Piazza et al 2009 ; Sujkowski et al 2015 ; Zheng et al 2017 ; Sujkowski and Wessells 2018 ; Blice-Baum et al 2019 ). These results indicate that measurements of locomotor function are valuable for examining heart health in fly models for HCM.…”

Section: Discussionmentioning

confidence: 99%

Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy

Tallo

Duncan

Yamamoto

et al. 2020

G3 Genes|Genomes|Genetics

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In cats, mutations in myosin binding protein C (encoded by the MYBPC3 gene) have been associated with hypertrophic cardiomyopathy (HCM). However, the molecular mechanisms linking these mutations to HCM remain unknown. Here, we establish Drosophila melanogaster as a model to understand this connection by generating flies harboring MYBPC3 missense mutations (A31P and R820W) associated with feline HCM. The A31P and R820W flies displayed cardiovascular defects in their heart rates and exercise endurance. We used RNA-seq to determine which processes are misregulated in the presence of mutant MYBPC3 alleles. Transcriptome analysis revealed significant downregulation of genes encoding small nucleolar RNA (snoRNAs) in exercised female flies harboring the mutant alleles compared to flies that harbor the wild-type allele. Other processes that were affected included the unfolded protein response and immune/defense responses. These data show that mutant MYBPC3 proteins have widespread effects on the transcriptome of co-regulated genes. Transcriptionally differentially expressed genes are also candidate genes for future evaluation as genetic modifiers of HCM as well as candidate genes for genotype by exercise environment interaction effects on the manifestation of HCM; in cats as well as humans.

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“…A wide range of laboratory aging models, ranging from Drosophila ( Blice-Baum et al, 2019 ) to mice ( Cohen, 2018 ), have been used to understand fundamental conserved principles of aging. However, lifespan and the aging phenotype are not universally correlated across different animal species.…”

Section: Introductionmentioning

confidence: 99%

Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish

Murphy

Santos-Ledo

Dhanaseelan

et al. 2021

Disease Models &Amp; Mechanisms

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As the human heart ages, the myocardium undergoes fibrotic remodelling, there is declining cardiovascular performance and eventual heart failure. It is suggested that exercise is an important intervention to ameliorate these changes. In this study we establish zebrafish as a laboratory model to understand how aging and exercise affect cardiomyocyte turnover. We show the zebrafish heart does not exhibit indeterminate growth but follows the pattern seen in human aging. In zebrafish, cardiomyocyte proliferation remains constant, but a late increase cell death underlies the pattern of initial cardiac growth and later fibrosis. These anatomical findings are corelated with the human like decline in cardiovascular performance reflected in voluntary swimming activity, critical swimming speed (Ucrit) and biomarkers of cardiac insufficiency. Whilst the vertebrate heart can respond to injury through cardiomyocyte proliferation, it is not known if a proliferative response occurs when the cardiovascular system is exposed to prolonged severe physiological stress, or if this changes with age. To investigate this, young and old adult zebrafish were challenged by 72 hours of enforced swimming in a purpose-built flume at levels close to maximal Ucrit. Whilst young adult fish produced a significant proliferative response older fish had a dramatically impaired response, provided by a smaller proliferative cardiomyocyte population. Finally, we asked if these aging responses could be improved by increased activity throughout adulthood. Whilst there was some improvement in the aged proliferative response the size of the reduced proliferative cardiomyocyte pool remained unchanged and importantly, there was increased myocardial fibrosis. The zebrafish heart thus provides a laboratory model to study cardiomyocyte turnover during aging and physiological stresses, revealing the important trade-off between preserving cardiovascular fitness through exercise and accelerated fibrotic change, whilst the available proliferative pool of cardiomyocytes continues to diminish.

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As time flies by: Investigating cardiac aging in the short-lived Drosophila model

Cited by 25 publications

References 251 publications

Drosophila Heart as a Model for Cardiac Development and Diseases

Drosophila Heart as a Model for Cardiac Development and Diseases

Heat shock proteins and small nucleolar RNAs are dysregulated in a Drosophila model for feline hypertrophic cardiomyopathy

Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish

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