Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Constitutive autophagy is important for the control of the quality of proteins and organelles to maintain cell function. Damaged proteins and organelles accumulate in aged organs. The level of autophagic activity decreases with aging. Autophagic activity is regulated by many factors, such as the insulin receptor-signaling pathway, the TOR pathway, Sirt1, and caloric restriction. Autophagy-related genes are known to be essential for the lifespan extension of flies, nematodes, and mice. The inhibition of autophagy decreases the lifespan, and on the other hand, the induction of autophagy can prolong the lifespan. Pharmacological intervention to extend the lifespan has demonstrated a crucial role for autophagy. Heart failure is an age-related disease, as the incidence increases with age. The autophagic activity of the heart decreases during aging. Cardiac-specific autophagy-deficient mice have shown no obvious phenotype up to 10 weeks of age. However, these mice began to die after the age of 6 months, with a significant increase in the left ventricular dimensions and a decrease in the fractional shortening of the left ventricle compared with control mice. This indicates that continuous constitutive autophagy during aging has a crucial role in maintaining cardiac structure and function.
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PMID:Role of autophagy in aging. 2234 71

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.
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PMID:Molecular mechanisms of heart failure: insights from Drosophila. 2790 93