1. Age-dependent diastolic heart failure in an in vivo Drosophila model
- Author
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Christian J. Peters, Matthew P. Klassen, Yuh Nung Jan, Shiwei Zhou, Lily Yeh Jan, and Hannah H Williams
- Subjects
0301 basic medicine ,Cardiac function curve ,medicine.medical_specialty ,Aging ,Heartbeat ,QH301-705.5 ,Science ,1.1 Normal biological development and functioning ,Pulsatile flow ,Diastole ,Diastolic ,Biology ,Cardiovascular ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Underpinning research ,Internal medicine ,cell biology ,medicine ,Animals ,Humans ,Systole ,Biology (General) ,Heart Failure ,Heart Failure, Diastolic ,General Immunology and Microbiology ,D. melanogaster ,cardiac physiology ,Animal ,General Neuroscience ,aging ,Diastolic heart failure ,ion channels ,General Medicine ,medicine.disease ,Potassium channel ,Cardiovascular physiology ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Drosophila melanogaster ,Heart Disease ,Disease Models ,Medicine ,Biochemistry and Cell Biology ,Neuroscience - Abstract
While the signals and complexes that coordinate the heartbeat are well established, how the heart maintains its electromechanical rhythm over a lifetime remains an open question with significant implications to human health. Reasoning that this homeostatic challenge confronts all pulsatile organs, we developed a high resolution imaging and analysis toolset for measuring cardiac function in intact, unanesthetized Drosophila melanogaster. We demonstrate that, as in humans, normal aging primarily manifests as defects in relaxation (diastole) while preserving contractile performance. Using this approach, we discovered that a pair of two-pore potassium channel (K2P) subunits, largely dispensable early in life, are necessary for terminating contraction (systole) in aged animals, where their loss culminates in fibrillatory cardiac arrest. As the pumping function of its heart is acutely dispensable for survival, Drosophila represents a uniquely accessible model for understanding the signaling networks maintaining cardiac performance during normal aging.
- Published
- 2017