Oxidative stress, mitochondria and mtDNA-mutator mice

Thompson, La Dora V.

doi:10.1016/j.exger.2006.10.018

Cited by 30 publications

(23 citation statements)

References 9 publications

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“…Altered respiratory-chain function may in turn result in increased (intrinsic) oxidative stress causing further damage. As one of the most relevant intrinsic sources of oxidative stress, the respiratory chain physiologically produces oxidants and radicals that cause cardiomyocyte aging [30,31] . Since cardiomyocytes are physiologically highly active cells, they comprise a large number of mitochondria, which make up to one third of total cellular mass.…”

Section: Oxidative Stress Oxidant Defense and Repair Mechanismsmentioning

confidence: 99%

The Aging Cardiomyocyte: A Mini-Review

Bernhard

Laufer²

2008

Gerontology

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Background: 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. Objective: 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. Methods: Review of the literature. Results: 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. Conclusion: 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.

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Section: Oxidative Stress Oxidant Defense and Repair Mechanismsmentioning

confidence: 99%

The Aging Cardiomyocyte: A Mini-Review

Bernhard

Laufer²

2008

Gerontology

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“…Altered respiratory-chain function can be viewed as one of the most relevant sources of oxidative stress in the myocardium [25,26]. This is because the energy turnover in cardiomyocytes is high, and mitochondria make up to one third of total cellular mass.…”

Section: Cardiomyocytes At Birth (~100 %)mentioning

confidence: 99%

How Cardiomyocytes Make the Heart Old

Papp¹,

Czuriga²,

Balogh³

et al. 2012

Current Pharmaceutical Biotechnology

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Naturally occurring decline in cardiovascular reserve with age associates with a combination of the reduction in cardiomyocyte number and altered cardiomyocyte function. Recent investigations suggested that about half of the cardiomyocytes is the same as at birth, while the other half of the cardiomyocytes is the result of cardiomyocyte renewal in the senescent heart. In addition, the total number of cardiomyocytes is estimated to be less by one third in the old heart than the number of cardiomyocytes at birth. Thus, the reduction in cardiomyocyte number of the aging heart cannot be fully compensated by cardiomyocyte renewal. Aging of long-lived differentiated myocardial cells, as well as of cardiac progenitor stem cells may contribute to an increased rate of apoptosis, and decreased capacity of cell duplication and/or differentiation. In addition, differentiated cardiomyocytes are prone for accumulating biological by-products of cellular metabolism and of incompletely processed oxidative insults. In this context, interactions between lysosomes and mitochondria may provide a mechanistic background for the age-dependent alterations in cardiac macromolecules. This reasoning postulates a direct relationship between the number of pro-oxidative, ill-functioning mitochondria and the amount of ballast- overloaded lysosomes in long-lived cardiomyocytes. Accumulation of biological garbage and telomere shortening might be considered as hallmarks of cardiomyocyte aging with implications for depressed cardiac function and cardiomyocyte renewal. Changes in protein expression together with posttranslational modifications of myocardial proteins affect excitation-contraction coupling and explain the declining mechanical function of the cardiomyocytes. Altogether, these changes represent a significant part of the reduced cardiovascular reserve in aged individuals.

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“…The transgenic mice in which POLG-α was mutated in cardiac tissue showed no evidence of increased oxidative protein damage, or of age-dependent increase in mtDNA oxidative damage [89]. The mutator mouse, in which POLG-α-deficient protein is expressed ubiquitously, develops a premature aging phenotype, owing to a significant increase in the levels of mtDNA point mutations and deletions [87], but it does not show signs of increased oxidative damage to mitochondrial proteins, lipids, or DNA [90] while in aged mutator mice, only a very mild increase in the level of mitochondrial hydrogen peroxide is observed [91]. …”

Section: The Mitochondrial Free Radical Theory Of Agingmentioning

confidence: 99%

Mechanisms linking mtDNA damage and aging

Pinto

Moraes

2015

Free Radical Biology and Medicine

161

105

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In the last century, considerable efforts were made to understand the role of mtDNA mutations and of oxidative stress in aging. The classic mitochondrial free radical theory of aging, in which mtDNA mutations cause genotoxic oxidative stress, which in turn creates more mutations, has been a central hypothesis in the field for decades. In the last few years, however, new elements have discredited this original theory. The major source of mitochondrial DNA mutations seems to come from replication errors and failure of the repair mechanisms, and the accumulation of these mutations as observed in aged organisms appears to occur by clonal expansion and are not caused by a reactive oxygen species-dependent vicious cycle. New hypotheses of how age-associated mitochondrial dysfunction may lead to aging are based on the role of reactive oxygen species as signaling molecules and on their role in mediating stress responses to age-dependent damage. Here, we review the changes that mtDNA undergoes during aging, and the past and most recent hypotheses linking these changes to the tissue failure observed in aging.

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Oxidative stress, mitochondria and mtDNA-mutator mice

Cited by 30 publications

References 9 publications

The Aging Cardiomyocyte: A Mini-Review

The Aging Cardiomyocyte: A Mini-Review

How Cardiomyocytes Make the Heart Old

Mechanisms linking mtDNA damage and aging

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