The aim of this study was to compare the central and peripheral components of cardiorespiratory fitness during incremental to maximal exercise between older men who were either recreational athletes (RA) or leisurely active (LA) men, i.e., those who fall between trained and untrained. This was a crosssectional study in which all subjects completed an exercise test on a cycle ergometer. Maximal oxygen consumption (VO2max) and ventilatory threshold (VT) were assessed using gas analysis, and central components of VO2max were assessed using a non-invasive thoracic bio-impedance device. VO2max (RA: 45.1±4.8 ml/kg/min; LA: 32.2±4.6 ml/kg/min, p≤0.001) and SV at maximal exercise (RA: 133.5±24.96 ml/beat; LA: 107.9±17.6 ml/beat, p=0.005) were higher in the RA group compared to the LA group. A plateau in SV occurred between 30-45 % of maximal exercise capacity in the RA group. No differences in SV were observed across workloads in the LA group. No differences in the calculated arterio-venous oxygen difference ((a-v)O2diff) were observed between groups. In conclusions, training volume appears to influence central components of cardiorespiratory fitness among a matched sample of older men who are neither trained nor untrained. This builds a case for increasing the volume of training to preserve cardiorespiratory fitness among older men., C. D. O'neill, D. S. Kimmerly, S. Dogra., and Obsahuje bibliografii
The relative length of telomeres measured in peripheral blood leukocytes is a commonly used system marker for biological aging and can also be used as a biomarker of cardiovascular aging. However, to what extent the telomere length in peripheral leukocytes reflects telomere length in different organ tissues is still unclear. Therefore, we have measured relative telomere length (rTL) in twelve different human tissues (peripheral blood leukocytes, liver, kidney, heart, spleen, brain, skin, triceps, tongue mucosa, intercostal skeletal muscle, subcutaneous fat, and abdominal fat) from twelve cadavers (age range of 29 week of gestation to 88 years old). The highest rTL variability was observed in peripheral leukocytes, and the lowest variability was found in brain. We found a significant linear correlation between leukocyte rTL and both intercostal muscle (R=0.68, P<0.02) and liver rTL (R=0.60, P<0.05) only. High rTL variability was observed between different organs from one individual. Furthermore, we have shown that even slight DNA degradation (modeled by sonication of genomic DNA) leads to false rTL shortening. We conclude that the rTL in peripheral leukocytes is not strongly correlated with the rTL in different organs., D. Dlouha, J. Maluskova, I. Kralova Lesna, V. Lanska, J. A. Hubacek., and Obsahuje bibliografii
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
Aged people are the most susceptible group to COVID-19 infection. Immunosenescence characterized by impairment of immune function with inflamm-aging contributes to pathophysiological alterations, among which endocrine and metabolic diseases are not exception. Diabetes, obesity along with impairment of disorders of thyroid functions are the most frequent ones, the common feature of which is failure of immune system including autoimmune processes. In the minireview we discussed how COVID-19 and aging impact innate and adaptive immunity, diabetes and selected neuroendocrine processes. Mentioned is also beneficial effect of vitamin D for attenuation of these diseases and related epigenetic issues. Particular attention is devoted to the role of ACE2 protein in the light of its intimate link with renin-angiotensin regulating system.
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
Mitochondria are considered central regulator of the aging process; however, majority of studies dealing with the impact of age on mitochondrial oxygen consumption focused on skeletal muscle concluding (although not uniformly) a general declining trend with advancing age. In addition, gender related differences in mitochondrial respiration have not been satisfactorily described yet. The aim of the present study was to evaluate mitochondrial oxygen consumption in various organs of aging male and female Fischer 344 rats at the ages of 6, 12 and 24 months. Mitochondrial respiration of homogenized (skeletal muscle, left and right heart ventricle, hippocampus, cerebellum, kidney cortex), gently mechanically permeabilized (liver) tissue or intact cells (platelets) was determined using high-resolution respirometry (oxygraphs O2k, Oroboros, Austria). The pattern of age-related changes differed in each tissue: in the skeletal muscle and kidney cortex of both sexes and in female heart, parameters of mitochondrial respiration significantly declined with age. Resting respiration of intact platelets displayed an increasing trend and it did not correlate with skeletal muscle respiratory states. In the heart of male rats and brain tissues of both sexes, respiratory states remained relatively stable over analyzed age categories with few exceptions of lower mitochondrial oxygen consumption at the age of 24 months. In the liver, OXPHOS capacity was higher in females than in males with either no difference between the ages of 6 and 24 months or even significant increase at the age of 24 months in the male rats. In conclusion, the results of our study indicate that the concept of general pattern of age-dependent decline in mitochondrial oxygen consumption across different organs and tissues could be misleading. Also, the statement of higher mitochondrial respiration in females seems to be conflicting, since the genderrelated differences may vary with the tissue studied, combination of substrates used and might be better detectable at younger ages than in old animals.