Caloric restriction delays cardiac ageing in rats: role of mitochondria
| العنوان: | Caloric restriction delays cardiac ageing in rats: role of mitochondria |
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| المؤلفون: | Ying Chen, Rolf-Edgar Silber, Susanne Rohrbach, Bernd Niemann, Hassan Issa |
| المصدر: | Cardiovascular Research. 88:267-276 |
| بيانات النشر: | Oxford University Press (OUP), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, Cardiac function curve, Aging, medicine.medical_specialty, Time Factors, Physiology, Apoptosis, Biology, Mitochondrion, medicine.disease_cause, Mitochondria, Heart, Ventricular Function, Left, Cell Line, Muscle hypertrophy, Rats, Sprague-Dawley, Ventricular Dysfunction, Left, Blood serum, Physiology (medical), Internal medicine, medicine, Animals, Myocytes, Cardiac, Cellular Senescence, Heart metabolism, Caloric Restriction, Membrane Potential, Mitochondrial, Age Factors, Rats, Oxidative Stress, Endocrinology, Ageing, Hypertrophy, Left Ventricular, RNA Interference, Apoptosis Regulatory Proteins, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, Oxidative stress |
| الوصف: | Aims We tested whether long-term caloric restriction (CR) corrects pre-existing manifestations of cardiac ageing in rats. Methods and results The age-specific effects of CR (−40%, 6 months) on mortality, left ventricular (LV) function, mitochondrial function, oxidative damage, and apoptosis were analysed in young (6 + 6 months) and senescent rats (24 + 6 months). CR in senescent rats significantly reduced mortality. LV and cardiomyocyte hypertrophy were reduced together with the mRNA expression and plasma concentrations of overload indicators BNP/ANP. Mitochondrial function was improved, resulting in lower oxidative damage and apoptotic activation. In particular, the pro-apoptotic Bcl-xS/Bcl-xL isoform pattern, mitochondrial translocation of Bax, release of cytochrome C into cytosol, and caspase-9 activation were reduced in comparison to age-matched rats on the control diet. However, CR resulted only in minor changes in young rats. Serum obtained from old control or CR rats was used for in vitro experiments. H9C2 cardiomyoblasts and adult rat ventricular cardiomyocytes preconditioned with CR serum demonstrated a low Bcl-xS/Bcl-xL ratio. H9C2 cells were resistant against H2O2-mediated loss of mitochondrial membrane potential, apoptosis activation, and reduced cell viability. Thus, beneficial effects of CR are mediated through circulating factors and can be mimicked with CR serum. However, this protection critically depended on a high Bcl-xL protein expression as seen after siRNA-mediated Bcl-xL knockdown. Conclusion CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation and by preventing deterioration in LV function. Therefore, interventions that mimic these effects of CR may represent an additional therapeutic option for the aged or failing heart. |
| تدمد: | 1755-3245 0008-6363 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b168a187049f275969bfad85b78d1a98Test https://doi.org/10.1093/cvr/cvq273Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b168a187049f275969bfad85b78d1a98 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17553245 00086363 |
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