Aging and CaMKII Alter Intracellular Ca2+ Transients and Heart Rhythm in Drosophila melanogaster

Santalla, Manuela; Valverde, Carlos; Harnichar, Alejandro Ezequiel; Lacunza, Ezequiel; Aguilar-Fuentes, Javier; Mattiazzi, Alicia; Ferrero, Paola

doi:10.1371/journal.pone.0101871

Cited by 30 publications

(39 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, increased free cellular Ca2 + activates CaMKII, leading to phosphorylation of proteins involved in Ca2 + handling [13]. In Drosophila , cardiac-specific inhibition of CaMKII reduces heart rate and increases the incidence of asystole while overexpression of CaMKII increases spontaneous heart rate and reduces arrhythmias [14]. Because CaMKII function is conserved from flies to mammals, the modulation of Ca2 + handling via CaMKII targeting may address problems associated with cardiac aging in humans.…”

Section: Ion Channel Proteins Contribute To Heart Failurementioning

confidence: 99%

Molecular mechanisms of heart failure: insights from Drosophila

et al. 2016

View full text Add to dashboard Cite

Heart failure places an enormous burden on health and economic systems worldwide. It is a complex disease that is profoundly influenced by both genetic and environmental factors. Neither the molecular mechanisms underlying heart failure nor effective prevention strategies are fully understood. Fortunately, relevant aspects of human heart failure can be experimentally studied in tractable model animals, including the fruit fly, Drosophila, allowing the in vivo application of powerful and sophisticated molecular genetic and physiological approaches. Heart failure in Drosophila, as in humans, can be classified into dilated cardiomyopathies and hypertrophic cardiomyopathies. Critically, many genes and cellular pathways directing heart development and function are evolutionarily conserved from Drosophila to humans. Studies of molecular mechanisms linking aging with heart failure have revealed that genes involved in aging-associated energy homeostasis and oxidative stress resistance influence cardiac dysfunction through perturbation of IGF and TOR pathways. Importantly, ion channel proteins, cytoskeletal proteins, and integrins implicated in aging of the mammalian heart have been shown to play significant roles in heart failure. A number of genes previously described having roles in development of the Drosophila heart, such as genes involved in Wnt signaling pathways, have recently been shown to play important roles in the adult fly heart. Moreover, the fly model presents opportunities for innovative studies that cannot currently be pursued in the mammalian heart because of technical limitations. In this review, we discuss progress in our understanding of genes, proteins, and molecular mechanisms that affect the Drosophila adult heart and heart failure.

show abstract

Section: Ion Channel Proteins Contribute To Heart Failurementioning

confidence: 99%

Molecular mechanisms of heart failure: insights from Drosophila

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Old (5-7 weeks of age) flies also have altered ion channel expression and significantly more cardiac arrhythmias, such as asystole and fibrillation, than young (1 week) flies (Ocorr et al 2007). Old flies also show a longer Ca 2+ transient decay time, which causes delayed relaxation and a slower heart rate with age (Santalla et al 2014).…”

Section: Age-related Cardiac Dysfunction In Drosophilamentioning

confidence: 99%

“…The Ca 2+ -calmodulin-dependent protein kinase II (CaMKII) is activated by increased free Ca 2+ in the cell and phosphorylates a number of proteins involved in Ca 2+ handling, including phospholamban, the ryanodine receptor (RyR) and the voltage-gated sodium channel Na V 1.5 (Santalla et al 2014). Cardiac-specific overexpression of CaMKII reduces age-related arrhythmias in flies.…”

Section: Non-structural Hypertrophy Genes Can Cause Premature Cardiacmentioning

confidence: 99%

“…By contrast, when dPsn is over-expressed in the fly heart, RyR gene levels are reduced which may decrease intracellular Ca 2+ levels. De-regulation of key Ca 2+ handling genes such as dSERCA, RyR and CaMKII is likely to contribute to the longer Ca 2+ transient decay time seen in old fly hearts which delays relaxation in the heart leading to a slower heart rate with age (Santalla et al 2014). dPsn may play a role in this mechanism.…”

Section: Alzheimer's and Huntington Genes Contribute To Cardiac Ageingmentioning

confidence: 99%

“…Old flies also show a longer Ca 2+ transient decay time, which causes delayed relaxation and a slower heart rate with age (Santalla et al . ).…”

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Genetic manipulation of cardiac ageing

Cannon

Bodmer

2015

The Journal of Physiology

View full text Add to dashboard Cite

Ageing in humans is associated with a significant increase in the prevalence of cardiovascular disease. We still do not fully understand the molecular mechanisms underpinning this correlation. However, a number of insights into which genes control cardiac ageing have come from studying hearts of the fruit fly, Drosophila melanogaster. The fly's simple heart tube has similar molecular structure and basic physiology to the human heart. Also, both fly and human hearts experience significant age-related morphological and functional decline. Studies on the fly heart have highlighted the involvement of key nutrient sensing, ion channel and sarcomeric genes in cardiac ageing. Many of these genes have also been implicated in ageing of the mammalian heart. Genes that increase oxidative stress, or are linked to cardiac hypertrophy or neurodegenerative diseases in mammals also affect cardiac ageing in the fruit fly. Moreover, fly studies have demonstrated the potential of exercise and statins to treat age-related cardiac disease. These results show the value of Drosophila as a model to discover the genetic causes of human cardiac ageing.

show abstract

Heart mechanical and hemodynamic parameters of a beetle, Tenebrio molitor, at selected ages

Pacholska-Bogalska

Szymczak

Marciniak

et al. 2018

Arch Insect Biochem Physiol

View full text Add to dashboard Cite

The physiological processes that occur during the aging of insects are poorly understood. The aim of this study was to describe the changes in contractile activity and hemodynamic parameters of the heart that take place as the coleopteran beetle, Tenebrio molitor, ages. The frequency of heart contractions in beetles that had just undergone metamorphosis (median 24.7 beats/min) was significantly lower than the frequency of heart contractions in older beetles. In 56% of beetles that were < 1 week of age, a pattern of contractile activity with alternating periods of higher and lower contraction frequency was detected, suggesting that some posteclosion developmental processes occur during the first week of adulthood. All beetles that were 1 week of age showed a regular rhythm of heart contractions (median 72 beats/min). In older beetles, abnormalities such as heart arrhythmias or heart arrest were observed. The incidence of arrhythmia as well as the arrhythmicity index was highest in beetles that were 8-18 weeks old. The calculated stroke volume (SV) was also found to increase from eclosion to 12 weeks of age, and then decreased as adults aged further. Interestingly, cardiac output increased gradually, but the ejection fraction did not change significantly with age.

show abstract

Aging and CaMKII Alter Intracellular Ca2+ Transients and Heart Rhythm in Drosophila melanogaster

Cited by 30 publications

References 41 publications

Molecular mechanisms of heart failure: insights from Drosophila

Molecular mechanisms of heart failure: insights from Drosophila

Genetic manipulation of cardiac ageing

Heart mechanical and hemodynamic parameters of a beetle, Tenebrio molitor, at selected ages

Contact Info

Product

Resources

About