Age-dependent diastolic heart failure in an in vivoDrosophilamodel.
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, unanesthetizedDrosophila 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,Drosophilarepresents a uniquely accessible model for understanding the signaling networks maintaining cardiac performance during normal aging.
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Matthew P
0000-0002-3633-2512
MP
Klassen
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Christian J
CJ
Peters
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Shiwei
S
Zhou
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Hannah H
HH
Williams
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.|Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Lily Yeh
LY
Jan
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
Yuh Nung
YN
Jan
D000818:Animals; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D054144:Heart Failure, Diastolic / Q000503:physiopathology*; D006801:Humans
D. melanogaster; aging; cardiac physiology; cell biology; ion channels