The Aging Cardiomyocyte: A Mini-Review
Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria. Gerontology
(Impact Factor: 3.06).
02/2008; 54(1):24-31. DOI: 10.1159/000113503
Aging per se is a risk factor for reduced cardiac function and heart diseases, even when adjusted for aging-associated cardiovascular risk factors. Accordingly, aging-related biochemical and cell-biological changes lead to pathophysiological conditions, especially reduced heart function and heart disease.
In this review, we summarize the changes that occur as the heart ages from youth to old age on the basis of the cardiac myocyte. Aging phenotypes and underlying mechanisms shall be discussed that affect cardiomyocyte repair, signaling, structure, and function.
Review of the literature.
The following factors play vital roles in the aging of cardiomyocytes: oxidative stress, inflammation, cellular protection and repair, telomere integrity, survival and death, metabolism, post-translational modifications, and altered gene expression. Importantly, non-cardiomyocyte-based aging processes (vascular, fibroblast, extracellular matrix, etc.) in the heart will interfere with cardiomyocyte aging and cardiac function.
Based on our analyses, we postulate that the physiological aging process of the heart and of the cardiomyocyte is primarily driven by intrinsic aging factors. However, extrinsic aging factors, e.g. smoking, also make an important contribution to pathologically accelerated aging of the heart.
Available from: Verónica Guarner
- "Advanced age is a marker of poor prognosis ; 75% of all myocardial infarction - related deaths occur after the age of 70 and the greater preexisting cardiovascular load of prior myocardial infarction and congestive heart failure . After myocardial infarction , these patients are highly prone to develop heart failure through adverse left ventricular remodeling , including greater infarct expansion , impaired infarct healing and , importantly , exaggerated and prolonged inflammatory response ( Bernhard and Laufer , 2008 ) . Aging may adversely affect left ventricular remodeling leading to progressive dilatation through modification of the inflammatory response after myocardial infarction ( Valentina et al . "
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ABSTRACT: Aging impairs blood vessel function and leads to cardiovascular disease. The mechanisms underlying the age-related endothelial, smooth muscle and extracellular matrix vascular dysfunction are discussed. Vascular dysfunction is caused by: 1) Oxidative stress enhancement. 2) Reduction of nitric oxide (NO) bioavailability, by diminished NO synthesis and/or augmented NO scavenging. 3) Production of vasoconstrictor/vasodilator factor imbalances. 4) Low-grade pro-inflammatory environment. 5) Impaired angiogenesis. 5) Endothelial cell senescence. The aging process in vascular smooth muscle is characterized by: 1) Altered replicating potential. 2) Change in cellular phenotype. 3) Changes in responsiveness to contracting and relaxing mediators. 4) Changes in intracellular signaling functions.
Systemic arterial hypertension is an age-dependent disorder, and almost half of the elderly human population is hypertensive. The influence of hypertension on the aging cardiovascular system has been studied in models of hypertensive rats. Treatment for hypertension is recommended in the elderly. Lifestyle modifications, natural compounds and hormone therapies are useful for initial stages and as supporting treatment with medication but evidence from clinical trials in this population is needed. Since all antihypertensive agents can lower blood pressure in the elderly, therapy should be based on its potential side effects and drug interactions.
Ageing research reviews 10/2014; 18. DOI:10.1016/j.arr.2014.10.001 · 4.94 Impact Factor
Available from: Kuo-Chu Chang
- "Several molecular mechanisms, including oxidative stress, inflammation and post-translational modifications, have been postulated for mechanical defects in cardiovascular ageing (Bernhard & Laufer, 2008). Among these, an increase in protein modification by advanced glycation end-products (AGEs) has been proposed as the primary basis for ageing-associated arterial stiffening and myocardial dysfunction (Lakatta, 1993). "
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ABSTRACT: What is the central question of this study? This study aimed to investigate the hypothesis that pyridoxamine, one of the three natural forms of vitamin B6, can protect against myocardial relaxation of senescent animals by targeting arterial stiffening and contractile dysfunction of the left ventricle. What is the main finding and its importance? We found that treating the senescent rats with pyridoxamine for 5 months might improve myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor.
Experimental physiology 09/2014; 99(11). DOI:10.1113/expphysiol.2014.082008 · 2.67 Impact Factor
Available from: Caroline Kumsta
- "For example, the incidence of heart failure and atrial fibrillation is markedly increased in the elderly (Lakatta & Levy, 2003; Roger et al., 2011), which suggests that aging per se is a major risk factor for heart disease. It is well known that the heart undergoes many age-related functional and structural changes (Khan et al., 2002; Bernhard & Laufer, 2008). However, the control mechanisms of cardiacintrinsic aging, and their coordination with organismal aging, remain elusive. "
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ABSTRACT: Cardiac performance decreases with age, which is a major risk factor for cardiovascular disease and mortality in the aging human population, but the molecular mechanisms underlying cardiac aging are still poorly understood. Investigating the role of integrin-linked kinase (ilk) and β1-integrin (myospheroid, mys) in Drosophila, which colocalize near cardiomyocyte contacts and Z-bands, we find that reduced ilk or mys function prevents the typical changes of cardiac aging seen in wildtype, such as arrhythmias. In particular, the characteristic increase in cardiac arrhythmias with age is prevented in ilk and mys heterozygous flies with nearly identical genetic background, and they live longer, in line with previous findings in Caenorhabditis elegans for ilk and in Drosophila for mys. Consistent with these findings, we observed elevated β1-integrin protein levels in old compared with young wild-type flies, and cardiac-specific overexpression of mys in young flies causes aging-like heart dysfunction. Moreover, moderate cardiac-specific knockdown of integrin-linked kinase (ILK)/integrin pathway-associated genes also prevented the decline in cardiac performance with age. In contrast, strong cardiac knockdown of ilk or ILK-associated genes can severely compromise cardiac integrity, including cardiomyocyte adhesion and overall heart function. These data suggest that ilk/mys function is necessary for establishing and maintaining normal heart structure and function, and appropriate fine-tuning of this pathway can retard the age-dependent decline in cardiac performance and extend lifespan. Thus, ILK/integrin-associated signaling emerges as an important and conserved genetic mechanism in longevity, and as a new means to improve age-dependent cardiac performance, in addition to its vital role in maintaining cardiac integrity.
Aging cell 01/2014; 13(3). DOI:10.1111/acel.12193 · 6.34 Impact Factor
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