Quality control systems in cardiac aging (original) (raw)
Related papers
Protein and Mitochondria Quality Control Mechanisms and Cardiac Aging
Cells
Cardiovascular disease (CVD) is the number one cause of death in the United States. Advancing age is a primary risk factor for developing CVD. Estimates indicate that 20% of the US population will be ≥65 years old by 2030. Direct expenditures for treating CVD in the older population combined with indirect costs, secondary to lost wages, are predicted to reach $1.1 trillion by 2035. Therefore, there is an eminent need to discover novel therapeutic targets and identify new interventions to delay, lessen the severity, or prevent cardiovascular complications associated with advanced age. Protein and organelle quality control pathways including autophagy/lysosomal and the ubiquitin-proteasome systems, are emerging contributors of age-associated myocardial dysfunction. In general, two findings have sparked this interest. First, strong evidence indicates that cardiac protein degradation pathways are altered in the heart with aging. Second, it is well accepted that damaged and misfolded pro...
Oxidative Medicine and Cellular Longevity, 2014
The heart is highly sensitive to the aging process. In the elderly, the heart tends to become hypertrophic and fibrotic. Stiffness increases with ensuing systolic and diastolic dysfunction. Aging also affects the cardiac response to stress. At the molecular level, the aging process is associated with accumulation of damaged proteins and organelles, partially due to defects in protein quality control systems. The accumulation of dysfunctional and abnormal mitochondria is an important pathophysiological feature of the aging process, which is associated with excessive production of reactive oxygen species. Mitochondrial fusion and fission and mitochondrial autophagy are crucial mechanisms for maintaining mitochondrial function and preserving energy production. In particular, mitochondrial fission allows for selective segregation of damaged mitochondria, which are afterward eliminated by autophagy. Unfortunately, recent evidence indicates that mitochondrial dynamics and autophagy are pr...
Metabolic targets in cardiac aging and rejuvenation
The Journal of Cardiovascular Aging, 2022
Cardiac aging is accompanied by progressive loss of cellular function, leading to impaired heart function and heart failure. There is an urgent need for efficient strategies to combat this age-related cardiac dysfunction. A growing number of events suggest that age-related cardiac diseases are tightly related to metabolic imbalance. This review summarizes recent findings concerning metabolic changes during cardiac aging and highlights the therapeutic approaches that target metabolic pathways in cardiac aging.
Cardiac aging in mice and humans: the role of mitochondrial oxidative stress
Trends in cardiovascular medicine, 2009
Age is a major risk factor for cardiovascular diseases, not only because it prolongs exposure to several other cardiovascular risks, but also owing to intrinsic cardiac aging, which reduces cardiac functional reserve, predisposes the heart to stress, and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, including left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenuated in mice overexpressing catalase targeted to mitochondria. These findings demonstrate the critical role of mitochondrial reactive oxygen species in cardiac aging and support the potential application of mitochondrial antioxi...
ABSTRACTBACKGROUNDDysregulated proteostasis leading to accumulation of misfolded proteins, electron-dense aggregates (lipofuscin, LF), desmin preamyloid oligomers (PAOs), and proteotoxic stress is a hallmark of aging. We investigated how efficiently proteostatic adaptations to chronic cardiac cyclic adenosine monophosphate (cAMP)-dependent stress change with aging, in mice harboring a marked, cardiac-specific over-expression of adenylyl cyclase VIII (TGAC8).METHODSProtein quality control (PQC) mechanisms (ubiquitin proteasome system (UPS) and autophagy), including mitophagy, in TGAC8and wild time littermates (WT) were evaluated in left ventricle (LV) at 3-4 months and at 17-21 months of age. Autophagy flux was evaluated in response to the lysosomotropic agent chloroquine (CQ), and protein synthesis was assessed according to the SUnSET puromycin method.RESULTSAt 3-4 months of age, established autophagy markers such as the microtubule-associated protein 1 light chain 3 (LC3), p62, and...