Considering the preexisting influence of the process of natural aging on antioxidant enzymes activity and the level of lipid peroxidation, the age of the rats at which D-galactose (D-gal) treatment is started could strongly impact the development of D-gal induced senescence. To eval uate this, we subjected 1, 3 and 15 months old rats to D-gal treatment in parallel with having appropriate placebos (0.9 % saline). Our results showed elevated glutathione peroxidase (GPx) acti vity and no significant changes in superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) activity or malondialdehyde (MDA) levels in relation to natural aging. In mature and aged senescent livers we observed positive correlation between increased ratio R=SOD/(GPx+CAT) and increased MDA concentration. MDA levels seemed to correlate positively with the age of the animals at which D-gal treatment had started. In the case of 3 and 15 months old rats there was D-gal induced decrease in SOD and GR activity, but this effect of the treatment was not observed in 1 month old rats. Our results imply that the changes in the antioxidant enzyme activities are not only under the influence of the D-gal overload, but also depend on the developmental stage of the rats. According to our resu lts, with regard to enzymatic antioxidant capacity and the level of lipid peroxidation, the best age for induction of senescence is somewhere after the third month., N. Hadzi-Petrushev, V. Stojkovski, D. Mitrov, M. Mladenov., and Obsahuje bibliografii
a1_Reduced tolerance to ischemia/reperfusion (IR) injury has been shown in elder human and animal hearts, however, the onset of this unfavorable phenotype and cellular mechanisms behind remain unknown. Moreover, aging may interfere with the mechanisms of innate cardioprotection (preconditioning, PC) and cause defects in protective cell signaling. We studied the changes in myocardial function and response to ischemia, as well as selected proteins involved in “pro-survival” pathways in the hearts from juvenile (1.5 months), younger adult (3 months) and mature adult (6 months) male Wistar rats. In Langendorffperfused hearts exposed to 30-min ischemia/2-h reperfusion with or without prior PC (one cycle of 5-min ischemia/5-min reperfusion), we measured occurrence of reperfusion-induced arrhythmias, recovery of contractile function (left ventricular developed pressure, LVDP, in % of pre-ischemic values), and size of infarction (IS, in % of area at risk size, TTC staining and computerized planimetry). In parallel groups, LV tissue was sampled for the detection of protein levels (WB) of Akt kinase (an effector of PI3-kinase), phosphorylated (activated) Akt (p-Akt), its target endothelial NO synthase (eNOS) and protein kinase Cε (PKCε) as components of “pro-survival” cascades. Maturation did not affect heart function, however, it impaired cardiac response to lethal IR injury (increased IS) and promoted arrhythmogenesis. PC reduced the occurrence of malignant arrhythmias, IS and improved LVDP recovery in the younger animals, while its efficacy was attenuated in the mature adults. Loss of PC protection was associated with age-dependent reduced Akt phosphorylation and levels of eNOS and PKCε in the hearts of mature animals compared with the younger ones, as well as with a failure of PC to upregulate these proteins., a2_Agingrelated alterations in myocardial response to ischemia may be caused by dysfunction of proteins involved in protective cell signaling that may occur already during the process of maturation., L. Griecsová, V. Farkašová, I. Gáblovský, V. K. M. Khandelwal, I. Bernátová, Z. Tatarková, P. Kaplan, T. Ravingerová., and Obsahuje bibliografii
Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15-and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions., Z. Tatarková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Accumulation of oxidative damage has been implicated to be a major causative factor in the decline in physiological functions that occur during the aging process. The mitochondrial respiratory chain is a powerful so urce of reactive oxygen species (ROS), considered as the pathogen ic agent of many diseases and aging. L-malate, a tricarboxylic acid cycle intermediate, plays an important role in transporting NADH from cytosol to mitochondria for energy production. Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. In the present study we focused on the effect of L-malate on the activities of electron transport chain in young and aged rats. We found that mitochondrial membrane potential (MMP) and the activities of succinate dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats were significantly decreased when compared to young control rats. Supplementation of L-malate to aged rats for 30 days slightly increased MMP and improved the activities of NADH-dehydrogenase, NADH-cytochrome c oxidoreductase and cytochrome c oxidase in liver of aged rats when compared with aged control rats. In young rats, L-malate administration increased only the activity of NADH-dehydrogenase. Our result suggested that L-malate could improve the activities of electron transport chain enzymes in aged rats., J.-L. Wu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
This study was undertaken to in vestigate the effects of lower body positive pressure (LBPP) on cardiovascular responses during a 15-min walking trial in young (22.1±0.4 years) and elderly women (67.8±1.1 years). The application of 20 mm Hg LBPP reduced ground reaction forces by 31.2±0.5 kgw in both groups. We hypothesized that cardiovascular responses to LBPP during walking were different between the young and elderly subjects. Applying 20 mm Hg of LBPP increased diastolic and mean blood pressure but not systolic blood pressure in both groups. LBPP- induced reduction in heart rate (HR) occurred more quickly in the young group compared to the elderly group (p<0.05). Applying LBPP also decreased double product (systolic blood pressure x HR) in both groups, suggesting that LBPP reduces myocardial oxygen consumption during exercise. These results suggest that heart rate responses to LBPP during exercise vary with increasing age., T. Sota ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Spinal deformities such as scoliosis and kyphosis are incurable, and can lead to decreased physical function, pain, and reduced quality of life. Despite much effort, no clear therapies for the treatment of these conditions have been found. Therefore, the development of an animal model for spinal deformity would be extremely valuable to our understanding of vertebral diseases. In this study, we demonstrate that mice deficient in the mitochondrial enzyme isocitrate dehydrogenase 2 (IDH2) develop spinal deformities with aging. We use morphological analysis as well as radiographic and micro-CT imaging of IDH2-deficient mice to characterize these deformities. Histological analysis showed increased abnormalities in IDH2-deficient mice compared to wild type mice. Taken together, the results suggest that IDH2 plays a critical role in maintaining the spinal structure by affecting the homeostatic balance between osteoclasts and osteoblasts. This indicates that IDH2 might be a potent target for the development of therapies for spinal deformities. Our findings also provide a novel animal model for vertebral disease research., U. Chae, N.-R. Park, E. S. Kim, J.-Y. Choi, M. Yim, H.-S. Lee, S.-R. Lee, S. Lee, J.-W. Park, D.-S. Lee., and Obsahuje bibliografii
The aging process is associated with a decline in mitochondrial functions. Mitochondria dysfunction is involved in initiation and progression of many health problems including neuromuscular, metabolic and cardiovascular diseases. It is well known that endurance exercise improves mitochondrial function, especially in the elderly. However, recent studies have demonstrated that resistan ce training lead also to substantial increases in mitochondrial function in skeletal muscle. A comprehensive understanding of the cellular mechanisms involved in the skeletal muscle mitochondrial adaptations to exercise training in healthy elderly subjects, can help practitioners to design and prescribe more effective exercise trainings., M. M. Ziaaldini, S. R. A. Hosseini, M. Fathi., and Obsahuje bibliografii
Understanding mitochondrial role in normal physiology and pathological conditions has proven to be of high importance as mitochondrial dysfunction is connected with a number of disorders as well as some of the most common diseases (e.g. diabetes or Parkinson’s disease). Modeling mitochondrial dysfunction has been difficult mainly due to unique features of mitochondrial genetics. Here we discuss some of the most important mouse models generated so far and lessons learned from them., S. A. Dogan, A. Trifunovic., and Obsahuje bibliografii a bibliografické odkazy
An ontogenetic study of ecto-ATPase activity and the content of enzyme proteins was assessed in the caudate nucleus and hippocampal synaptic plasma membranes isolated from rats at various ages (15, 30, 90, 180 and 365 days). The ontogenetic profile revealed that the enzyme activities in both brain areas were the highest on day 30 and 365, while the ecto-ATPase protein abundance was the highest on day 15 after birth. Possible explanation for obtained ontogenetic profile and the discrepancy between activity and abundance may reside in the fact that ecto-ATPase during development could exert additional roles other than those related to metabolism of ATP. It is likely that ecto-ATPase, regulating the concentration of ATP and adenosine in synaptic cleft, has important role in the processes of brain development and aging., A. Banjac, N. Nedeljković, A. Horvat, D. Kanazir, G. Nizekić., and Obsahuje bibliografii
a1_Cíle. Propoziční hustota (PH), psycholingvistické měřítko, koreluje s kognitivní kapacitou ve starším věku. Tato studie zjišťuje rozdíly v propoziční hustotě v orálních výpovědích na téma z nedávné minulosti u osob zdravých a s mírnou kognitivní poruchou (MKP). MKP je v současnosti přijímána jako prodromální stádium Alzheimerovy nemoci (AN). Soubor. Soubor zahrnoval 33 osob s MKP a 32 zdravých kontrol (průměrný věk 73 let). Obě skupiny byly vyrovnané, a to co do věku a úrovně dosaženého vzdělání. Dle očekávání se lišily v skóru MMSE, který je považován za zjednodušené vyjádření úrovně kognitivního stavu. Hypotézy. Nižší PH byla očekávána u osob s MKP, neboť úkol zatěžoval vybavení z novopaměti. Přičemž obtíž se zapamatováním nových informací, a tedy i vybavením z novopaměti, je jedním z jádrových symptomů AN., a2_Analýza a výsledky. Průměrná propoziční hustota u pacientů s MKP činila 48,74 % (sm. odch. 5,78), u kontrolního vzorku seniorů bez kognitivních poruch to bylo 53,06 % (sm. odch. 4,56). Studentův t-test prokázal statisticky významný rozdíl mezi skupinami (p < 0,001). Cohenovo d 0,83 reprezentuje velký efekt příslušnosti ke skupině. Omezení. Nejpodstatnějším omezením této studie je heterogenita diagnostické jednotky MKP. Dalším omezením byla neznalost premorbidní kognitivní úrovně zdravých kontrol, proto je možné, že v kontrolní skupině byly osoby s již počínající kognitivní poruchou, jež byla při jednorázovém vyšetření nezachytitelná., b1_Objectives. It has been shown that propositional density (PD), which roughly corresponds to the number of ideas expressed in a text of given length, is related to cognitive performance in the older age. The present study investigated differences in propositional density in oral language production between healthy seniors and patients with mild cognitive impairment (MCI). MCI is generally accepted as a prodromal stage of Alzheimer’s disease (AD). Sample and setting. The sample included 33 MCI persons and 32 healthy controls (mean age 73 years). The groups were equivalent as for the age and education. As expected, there was a significant difference between Mini-Mental State Examination (MMSE) scores between the groups, with MMSE being a simplified measure of their cognitive status. Hypotheses. Lower PD was expected in MCI persons, as the task required recent past recall which is considered one of the early deficiencies in early AD and MCI due to AD., b2_Statistical analysis. Mean PD across groups was compared using the independent samples t-test. Results. Mean propositional density in MCI persons was 48,74% (SD 5,78), and in healthy controls 53,06% (SD 4,56). The difference was statistically significant (p<0,001). Cohen’s d 0,83 represents a large effect size for the group difference. Study limitations. The main limitation is the heterogeneity of the MCI group. Also, the detailed cognitive status of the healthy controls is unknown. Thus the group could include persons with some cognitive impairment which has not been detected yet., Hana Štěpánková, Filip Smolík, Martin Vyhnálek, Tomáš Nikolai, Karolína Horáková, Markéta Niederlová., and Obsahuje seznam literatury