BACKGROUND: Biological aging is a physiological process that can be altered by various factors. The presence of a chronic metabolic disease can accelerate aging and increase the risk of further chronic diseases. The aim of the study was to determine whether the presence of metabolic syndrome (MetS) affects levels of markers that are associated with, among other things, aging. MATERIAL AND METHODS: A total of 169 subjects (58 with MetS, and 111 without metabolic syndrome, i.e., non-MetS) participated in the study. Levels of telomerase, GDF11/15, sirtuin 1, follistatin, NLRP3, AGEs, klotho, DNA/RNA damage, NAD+, vitamin D, and blood lipids were assessed from blood samples using specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Telomerase (p < 0.01), DNA/RNA damage (p < 0.006) and GDF15 (p < 0.02) were higher in MetS group compared to non-MetS group. Only vitamin D levels were higher in the non-MetS group (p < 0.0002). Differences between MetS and non-MetS persons were also detected in groups divided according to age: in under 35-year-olds and those aged 35-50 years. CONCLUSIONS: Our results show that people with MetS compared to those without MetS have higher levels of some of the measured markers of biological aging. Thus, the presence of MetS may accelerate biological aging, which may be associated with an increased risk of chronic comorbidities that accompany MetS (cardiovascular, inflammatory, autoimmune, neurodegenerative, metabolic, or cancer diseases) and risk of premature death from all causes.
- Publikační typ
- časopisecké články MeSH
Background: Anthracycline cardiotoxicity is a well-known complication of cancer treatment, and miRNAs have emerged as a key driver in the pathogenesis of cardiovascular diseases. This study aimed to investigate the expression of miRNAs in the myocardium in early and late stages of chronic anthracycline induced cardiotoxicity to determine whether this expression is associated with the severity of cardiac damage. Method: Cardiotoxicity was induced in rabbits via daunorubicin administration (daunorubicin, 3 mg/kg/week; for five and 10 weeks), while the control group received saline solution. Myocardial miRNA expression was first screened using TaqMan Advanced miRNA microfluidic card assays, after which 32 miRNAs were selected for targeted analysis using qRT-PCR. Results: The first subclinical signs of cardiotoxicity (significant increase in plasma cardiac troponin T) were observed after 5 weeks of daunorubicin treatment. At this time point, 10 miRNAs (including members of the miRNA-34 and 21 families) showed significant upregulation relative to the control group, with the most intense change observed for miRNA-1298-5p (29-fold change, p < 0.01). After 10 weeks of daunorubicin treatment, when a further rise in cTnT was accompanied by significant left ventricle systolic dysfunction, only miR-504-5p was significantly (p < 0.01) downregulated, whereas 10 miRNAs were significantly upregulated relative to the control group; at this time-point, the most intense change was observed for miR-34a-5p (76-fold change). Strong correlations were found between the expression of multiple miRNAs (including miR-34 and mir-21 family and miR-1298-5p) and quantitative indices of toxic damage in both the early and late phases of cardiotoxicity development. Furthermore, plasma levels of miR-34a-5p were strongly correlated with the myocardial expression of this miRNA. Conclusion: To the best of our knowledge, this is the first study that describes alterations in miRNA expression in the myocardium during the transition from subclinical, ANT-induced cardiotoxicity to an overt cardiotoxic phenotype; we also revealed how these changes in miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: High indoxyl sulfate (IS) concentration is a serious problem for patients with CKD increasing the risk of cardiovascular diseases and CKD progression. Thus, the methods of decreasing the toxin concentrations are highly desired. The study aimed to discover the role of selected intestine-related factors on IS concentration. METHODS: We evaluated the impact of ABCG2 and ABCC2 polymorphisms influencing activity and protein intake by normalized protein catabolic rate. Additionally, we examined the relation of IS and uric acid (UA) that can share common elimination transporters. A monocentric, prospective, open cohort pilot study was performed on 108 patients undergoing dialysis treatment. RESULTS: The positive effect of residual diuresis on the reduction of IS levels was confirmed (p = 0.005). Also, an increase in IS depending on the dietary protein intake was confirmed (p = 0.040). No significant correlation between ABC gene polymorphisms was observed either, suggesting the negligible role of ABCG2 and ABCC2 in the elimination of IS in small bowel. The significant difference was observed for UA where ABCG2 421C>A (rs72552713) gene polymorphism was higher (505.3 μmol/L) in comparison with a wild-type genotype (360.5 μmol/L). CONCLUSION: No evidence of bowel elimination pathway via ABCC2 and ABCG2 transporters was found in renal replacement therapy patients.
Stárnutí je proces postupného snižování funkčních kapacit lidského těla, který vede k významnému vzestupu rizika úmrtí v čase. Ačkoliv se jedná o proces univerzální všem živočichům, není jeho rychlost stejná. Biomarkery stárnutí si kladou za cíl lépe popsat proces stárnutí na úrovni jedince, orgánu, tkáně nebo jednotlivých buněk. Slouží k odhadu rychlosti stárnutí a predikci pravděpodobnosti úmrtí. Měly by dobře vypovídat o aktuálním stavu organismu a zpřesňovat predikci vnímavosti osoby ke vzniku onemocnění, jeho průběhu a pravděpodobnosti výskytu komplikací a smrti. Jednoduché biomarkery měří jen jeden parametr nebo úzkou skupinu parametrů spolu souvisejících, které mají známou asociaci s věkem, ať jde o změny v průběhu stárnutí člověka nebo u laboratorního modelu. Můžeme je rozdělit na molekulární (vycházející ze znaků stárnutí), funkční (popisující snižující se funkční kapacity v průběhu stárnutí) a antropometrické (popisující strukturální změny). Složené biomarkery představují nejkomplexnější způsob měření biologického věku. Kombinují v sobě velké množství dat, která pomocí algoritmů, často postavených na umělé inteligenci, vyhodnocují. Do této skupiny patří i aktuálně nejrozšířenější metoda měření biologického věku – epigenetické hodiny (epigenetic clock). Cílem tohoto článku je přehledně rozdělit množství existujících markerů stárnutí do skupin a popsat jejich vztah ke stárnutí.
Aging is a process of gradual decline in the functional capacity of the human body that leads to a significant increase in the risk of death over time. Although it is a process universal to all animals, its rate is not the same. Biomarkers of aging aim to better describe the aging process at the level of the individual, organ, tissue, or single cell. They are used to estimate the rate of aging and predict the probability of death. They are good indication of the current state of the organism and are more accurate in predicting a person's susceptibility to disease, its progression and the likelihood of complications and death. Simple biomarkers measure only one parameter or a narrow group of related parameters that have a known association with age, in human or in a laboratory model. They can be divided into molecular (based on features of aging), functional (describing decreasing functional capacity during aging) and anthropometric (describing structural changes). Composite biomarkers are the most comprehensive way of measuring biological age. They combine a large amount of data, which they evaluate using algorithms often based on artificial intelligence. The most widely used method for measuring biological age in composite biomarkers is the epigenetic clock. The aim of this article is to review the many existing markers of aging and describe their relationship to aging.
- MeSH
- biologické markery * MeSH
- lidé MeSH
- stárnutí buněk genetika MeSH
- stárnutí * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Aging is a natural, gradual, and inevitable process associated with a series of changes at the molecular, cellular, and tissue levels that can lead to an increased risk of many diseases, including cancer. The most significant changes at the genomic level (DNA damage, telomere shortening, epigenetic changes) and non-genomic changes are referred to as hallmarks of aging. The hallmarks of aging and cancer are intertwined. Many studies have focused on genomic hallmarks, but non-genomic hallmarks are also important and may additionally cause genomic damage and increase the expression of genomic hallmarks. Understanding the non-genomic hallmarks of aging and cancer, and how they are intertwined, may lead to the development of approaches that could influence these hallmarks and thus function not only to slow aging but also to prevent cancer. In this review, we focus on non-genomic changes. We discuss cell senescence, disruption of proteostasis, deregualation of nutrient sensing, dysregulation of immune system function, intercellular communication, mitochondrial dysfunction, stem cell exhaustion and dysbiosis.
- MeSH
- lidé MeSH
- mezibuněčná komunikace MeSH
- nádory * MeSH
- stárnutí buněk genetika MeSH
- stárnutí * metabolismus MeSH
- zkracování telomer MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Aging is a natural process of gradual decrease in physical and mental capacity. Biological age (accumulation of changes and damage) and chronological age (years lived) may differ. Biological age reflects the risk of various types of disease and death from any cause. We selected potential biomarkers of aging - telomerase, AGEs, GDF11 and 15 (growth differentiation factor 11/15), sirtuin 1, NAD+ (nicotinamide adenine dinucleotide), inflammasome NLRP3, DNA/RNA damage, and klotho to investigate changes in their levels depending on age and sex. We included 169 healthy volunteers and divided them into groups according to age (under 35; 35-50; over 50) and sex (male, female; male and female under 35; 35-50, over 50). Markers were analyzed using commercial ELISA kits. We found differences in values depending on age and gender. GDF15 increased with age (under 30 and 35-50 p < 0.002; 35-50 and over 50; p < 0.001; under 35 and over 50; p < 0.001) as well as GDF11 (35-50 and over 50; p < 0.03; under 35 and over 50; p < 0.02), AGEs (under 30 and 35-50; p < 0.005), NLRP3 (under 35 over 50; p < 0.03), sirtuin 1 (35-50 and over 50; p < 0.0001; under 35 and over 50; p < 0.004). AGEs and GDF11 differed between males and females. Correlations were identified between individual markers, markers and age, and markers and sex. Markers that reflect the progression of biological aging vary with age (GDF15, GDF11, AGEs, NLRP3, sirtuin) and sex (AGEs, GDF11). Their levels could be used in clinical practice, determining biological age, risk of age-related diseases and death of all-causes, and initiating or contraindicating a therapy in the elderly based on the patient's health status.
- MeSH
- biologické markery MeSH
- DNA MeSH
- kostní morfogenetické proteiny MeSH
- lidé MeSH
- NAD * MeSH
- produkty pokročilé glykace MeSH
- protein NLRP3 MeSH
- růstové diferenciační faktory metabolismus MeSH
- senioři MeSH
- sirtuin 1 MeSH
- stárnutí genetika MeSH
- telomerasa * MeSH
- zdravotní stav MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
