Contractile Function and Ca&lt;sup&gt;2+&lt;/sup&gt; Transport System of Myocardium in Ageing

Frolkis, V.V.; Frol'kis, R. A.; Мхітарян, Л С; Shevchuk, V.G.; Fraifeld, Vadim E.; Vakulenko, L.G.; Syrový, I

doi:10.1159/000212932

Cited by 43 publications

(24 citation statements)

References 17 publications

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“…The Na + /Ca 2+ transporter is also energy dependent, and a decline in myocardial ATP levels would thus slow cardiac relaxation by decreasing the rate of Ca 2+ removal from the cytosol (30,31). It is notable that a general attribute of myocardial aging is a prolonged cytosolic calcium transient and slower myocardial relaxation rate (32,33).…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress in the aging rat heart is reversed by dietary supplementation with ( R )‐α‐lipoic acid

et al. 2001

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Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age-related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as measured by the rates of 2,7-dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not α-tocopherol. A significant age-related increase (P = 0.05) in steady-state levels of oxidative DNA damage was observed, as monitored by 8-oxo-2′-deoxyguanosine levels. To investigate whether dietary supplementation with (R)-α-lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN-93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA-supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation. Keywordsaging; cardiac myocytes; oxidative stress; lipoic acid Aging is associated with an increased incidence of cardiac arrhythmias and diastolic and systolic dysfunction, which may ultimately lead to heart failure. Heart failure alone is the leading cause of hospitalization, permanent disability, and death in persons over the age of HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript 65 (1) in the U.S. Because of the enormous suffering and health care burden that cardiac dysfunction causes, much effort has gone into understanding the mechanisms leading to agerelated myocardial decline. It has been difficult, however, to separate the effects of aging per se from those of age-associated diseases (atherosclerosis, diabetes, hypertension) on cardiac performance. Thus, the relative contribution of 'aging' to myocardial dysfunction is not well defined.Even though the mechanisms leading to alterations in cardiac performance are not well understood, there is reason to suspect increased oxidative stress to significantly contribute to myocardial dysfunction with age. It is generally agreed that isolated mitochondrial preparations from old compared to young hearts produce more reactive oxygen species (ROS), reflecting an age-related decline in coupling of electron transport to ATP production. These changes in mitochondria may lead to the reported increase in superoxide and hydrogen peroxide production in mitochondria prepared from old vs. young rats (2-4). Thus, it is conceiv...

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Section: Discussionmentioning

confidence: 99%

Oxidative stress in the aging rat heart is reversed by dietary supplementation with ( R )‐α‐lipoic acid

et al. 2001

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“…Aging alters cytosolic calcium handling. This has been clearly demonstrated in the heart where aging impairs the myocardial calcium transport system, calcium storage capacities, and contractile function (Besse et al., 1994; Feridooni, Dibb, & Howlett, 2015; Frolkis et al., 1988; Kaplan et al., 2007). This was recently confirmed in myocytes isolated from human right atria (Herraiz‐Martínez et al., 2015) and suggests a progressive decline in right atrial contractile function with age.…”

Section: Regulating Factors Of Mptp and Agingmentioning

confidence: 99%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

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SummaryThe cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.

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“…Damage to membrane lipids and proteins results in an alteration of fluidity and consequent disturbances of transport, permeability, response to regulatory stimuli and other membrane functions [36][37][38][39][40]. Nuclei of aged postmitotic cells are characterized by an increased content of heterochromatin and irregular surfaces, as well as by damage to nuclear proteins and DNA, such as cross-linking, single-and doublestrand breaks and various mutations that disturb DNA replication and transcription [41][42][43][44].…”

Section: Cellular Manifestations Of Ageingmentioning

confidence: 99%

Autophagy, organelles and ageing

Terman

Gustafsson

Brunk

2007

The Journal of Pathology

263

210

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As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy and other degradative systems, long-lived postmitotic cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells, progressively accumulate biological 'garbage' ('waste' materials). The latter include lipofuscin (a non-degradable intralysosomal polymeric substance), defective mitochondria and other organelles, and aberrant proteins, often forming aggregates (aggresomes). An interaction between senescent lipofuscin-loaded lysosomes and mitochondria seems to play a pivotal role in the progress of cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species. Increased oxidative stress, in turn, further enhances damage to both mitochondria and lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death.

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Contractile Function and Ca<sup>2+</sup> Transport System of Myocardium in Ageing

Cited by 43 publications

References 17 publications

Oxidative stress in the aging rat heart is reversed by dietary supplementation with ( R )‐α‐lipoic acid

Oxidative stress in the aging rat heart is reversed by dietary supplementation with ( R )‐α‐lipoic acid

Mitochondria and aging: A role for the mitochondrial transition pore?

Autophagy, organelles and ageing

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