Protection in the aged heart: preventing the heart-break of old age?

International audienceAdvanced glycation end products (AGEs) are considered as biomarkers of ageing and are associated with several degenerative diseases. Besides endogenous formation, significant amounts of AGEs are taken up with food. Although nutritional AGEs are considered as undesirable, proinflammatory agents, they may also enclose potentially beneficial antioxidants. We used rodent cardiac cells to evaluate if food AGEs, present in bread crust, can modify the cellular antioxidant defence. Mice were fed with bread crust containing diet to prove the in-vivo relevance for the heart. In mouse cardiac fibroblasts, bread crust extract induced a moderate elevation of ROS production causing an activation of p42/p44, p38 and NF-κB, followed by increased expression of antioxidative enzymes. Preconditioning studies demonstrated that this was sufficient to protect cardiac fibroblasts and rat adult cardiac myocytes against severe oxidative stress. Furthermore, mice, fed a bread crust containing diet, exhibited a similarly improved cardiac expression of antioxidative defence genes. The consumption of AGEs can therefore contribute to an improved antioxidant status of the heart, thus exhibiting cardioprotective effects in case of severe oxidative stress as in ischemia reperfusion injury. Also, these data show that the exclusive interpretation of circulating AGEs as pathophysiological biomarkers of ageing might be misleading

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“…Unfortunately, IP is not efficient in tissue from old humans (Juhaszova et al, 2005;Bartling et al, 2003).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Preconditioning with Maillard reaction products improves antioxidant defence leading to increased stress tolerance in cardiac cells

Ruhs

Naß

Bartling

et al. 2010

Experimental Gerontology

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“…This is probably related to the observed increased incidence of diabetes, hypertension, and heart failure in this population and to the associated activation of the adrenergic drive (Hu et al 2008). From data presented in the literature, the aged heart has a diminished functional and adaptive reserve capacity, an increased susceptibility to incur damage and a limited practical ability for repair/regeneration (Juhaszova et al 2005). The reduced tolerance to ischemic insult with aging is also noticed in the laboratory animal with a reduced recovery of the coronary flow and contractility during reperfusion occurring in mice (Azhar et al 1999;Willems et al 2003;Willems et al 2005) and rats (Leichtweis et al 2001;Xia et al 2003) as soon as they reach middle age.…”

Section: Introductionmentioning

confidence: 99%

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

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Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10-or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H 2 O 2 release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H 2 O 2 when they oxidize FADH 2 -linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration AGE (2011) of the coronary perfusion was explained by an increased mitochondrial ROS release related to the preservation of complex II activity during reperfusion.

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“…Aging is associated with a progressive decline in physiological reserves that reduces the capacity for work (Chantler et al, 2006;Goldspink, 2005) and increases the susceptibility to injury (Abete et al, 1996;Juhaszova et al, 2005;Lesnefsky et al, 1994;Maggioni et al, 1993). A case in point is the myocardium, an aerobic tissue with high energy demands dependent on mitochondrial oxidative phosphorylation (OxPhos) where aging precipitates organ failure during stress.…”

Section: Introductionmentioning

confidence: 99%

Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart

Preston¹,

Oberlin²,

Holmuhamedov³

et al. 2008

Mechanisms of Ageing and Development

124

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Aging is associated with progressive decline in energetic reserves compromising cardiac performance and tolerance to injury. Although deviations in mitochondrial functions have been documented in senescent heart, the molecular bases for the decline in energy metabolism are only partially understood. Here, high-throughput transcription profiles of genes coding for mitochondrial proteins in ventricles from adult (6-months) and aged (24-months) rats were compared using microarrays. Out of 614 genes encoding for mitochondrial proteins, 94 were differentially expressed with 95% downregulated in the aged. The majority of changes affected genes coding for proteins involved in oxidative phosphorylation (39), substrate metabolism (14) and tricarboxylic acid cycle (6). Compared to adult, gene expression changes in aged hearts translated into a reduced mitochondrial functional capacity, with decreased NADH-dehydrogenase and F0F1-ATPase complex activities and capacity for oxygen-utilization and ATP synthesis. Expression of genes coding for transcription co-activator factors involved in the regulation of mitochondrial metabolism and biogenesis were downregulated in aged ventricles without reduction in mitochondrial density. Thus, aging induces a selective decline in activities of oxidative phosphorylation complexes I and V within a broader transcriptional downregulation of mitochondrial genes, providing a substrate for reduced energetic efficiency associated with senescence.

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Protection in the aged heart: preventing the heart-break of old age?

Cited by 131 publications

References 130 publications

Preconditioning with Maillard reaction products improves antioxidant defence leading to increased stress tolerance in cardiac cells

Preconditioning with Maillard reaction products improves antioxidant defence leading to increased stress tolerance in cardiac cells

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart

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