The genetic control of aging is an intriguing and pervasive problem, but has been difficult to tackle. By studying genetically tractable model systems it has become clear in recent years that aging is indeed regulated/modulated by specific genes, such as insulin and its downstream effectors. How the aging process is orchestrated within an organism and how the functional and morphological decline of organ systems is initiated, coordinated and executed is still far from being understood. Since cardiac dysfunction is the most common cause of death in the elderly, it is of crucial importance to understand the progression and control of age-related changes in heart function. To date very little is known about the genetic mechanisms that control cardiac aging. We have recently implemented assays to study the genetic basis of cardiac aging in the simple Drosophila system, the only invertebrate genetic model system with a heart. Given the high degree of parallel genetic functions between flies and vertebrates in cardiogenesis, and given the strikingly common mechanisms that determine lifespan and rate of overall aging, it is likely that fundamental aspects of age-related changes of cardiac function and performance in flies are also conserved. Recent evidence indeed suggests that the fly's heart function is controlled by conserved aging genes and in ways that may turn out to be remarkably similar to vertebrates. The proposed studies are expected to provide a basic genetic understanding of age-dependent decline mechanisms in heart function that may serve as a prototype to guide similar studies in human cardiac aging and of age-related cardiac diseases. We propose to use the Drosophila model and its advanced molecular-genetic tools to study the control mechanisms by which the aging process of an individual organ, the heart, is regulated. For this purpose, we will first delineate the changes in cardiac function and fine-structure that occur with age (Aim la) and whether an age-dependent modulation of heart function (eg. by altered ion channel functions) also changes other aspects of cardiac aging. Then, we will study the genetic control of cardiac aging by insulin/TOR/JNK signaling (Aim 2a), including autonomous versus non-autonomous mechanisms (Aim 2b). It will be of particular interest to see whether manipulations that alter other aspects of functional aging (ie. immunity, gut, sleep) also influence cardiac aging. In order to discover new genes that are involved in cardiac aging, we will conduct a screen for modulators of the age-dependent changes in heart function (Aim 3).

Public Health Relevance

The combined outcome of this and the other projects on functional aging of this Program Project will provide new concepts and approaches to explore the coordination of the aging process within an organism. In particular, the proposed studies in this project will elucidate new ways by which the cardiac decline in heart function with age could be attenuated by heart-specific interventions. This would provide a prototype for similar approaches in mammals, including new therapeutics approaches to counteract adverse effects of cardiac aging in humans, and thus to increase the quality of life in the elderly

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-2 (J2))
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Sanford-Burnham Medical Research Institute
La Jolla
United States
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Zarndt, Rachel; Walls, Stanley M; Ocorr, Karen et al. (2017) Reduced Cardiac Calcineurin Expression Mimics Long-Term Hypoxia-Induced Heart Defects in Drosophila. Circ Cardiovasc Genet 10:
Cannon, Leah; Bodmer, Rolf (2016) Genetic manipulation of cardiac ageing. J Physiol 594:2075-83
Hardy, Christopher M; Birse, Ryan T; Wolf, Matthew J et al. (2015) Obesity-associated cardiac dysfunction in starvation-selected Drosophila melanogaster. Am J Physiol Regul Integr Comp Physiol 309:R658-67
Dissel, Stephane; Seugnet, Laurent; Thimgan, Matthew S et al. (2015) Differential activation of immune factors in neurons and glia contribute to individual differences in resilience/vulnerability to sleep disruption. Brain Behav Immun 47:75-85
Diop, Soda Balla; Bisharat-Kernizan, Jumana; Birse, Ryan Tyge et al. (2015) PGC-1/Spargel Counteracts High-Fat-Diet-Induced Obesity and Cardiac Lipotoxicity Downstream of TOR and Brummer ATGL Lipase. Cell Rep :
Diop, Soda Balla; Bodmer, Rolf (2015) Gaining Insights into Diabetic Cardiomyopathy from Drosophila. Trends Endocrinol Metab 26:618-27
Thimgan, Matthew S; Seugnet, Laurent; Turk, John et al. (2015) Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila. Sleep 38:801-14
Dissel, Stephane; Melnattur, Krishna; Shaw, Paul J (2015) Sleep, Performance, and Memory in Flies. Curr Sleep Med Rep 1:47-54
Ivy, Jessica R; Drechsler, Maik; Catterson, James H et al. (2015) Klf15 Is Critical for the Development and Differentiation of Drosophila Nephrocytes. PLoS One 10:e0134620
Lucey, Brendan P; Leahy, Averi; Rosas, Regine et al. (2015) A new model to study sleep deprivation-induced seizure. Sleep 38:777-85

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