The effect long term exercise on the content of extracellular vesicles isolated from human blood
Extracellular vesicles are membrane-surrounded structures derived from different cells. Their size can vary from 30 nm to several micrometers. Extracellular vesicles are considered to be a means of intercellular communication by which cells can transfer proteins, lipids, and nucleic acids to each other.
Research in recent years has shown that exercise triggers the release and entry of extracellular vesicles into the circulation, which is likely to contribute to exercise-related adaptive systemic signalling through the delivery of various biomolecules.
In our research, we aimed to investigate the effect of decades of exercise on the content of extracellular vesicles in different sizes circulating in human blood. Blood samples were collected from 193 senior riders at the 2019 World Rowing Masters Championships at Lake Venice. 112 subject were enrolled in the control group and its members, unlike the senior rowers, were untrained individuals.
By isolating extracellular vesicles from the collected blood samples and analysing the biomolecular content, we may come closer to understand the signalling pathways that may be responsible for the systemic effects of exercise.
Effect of acute intense physical exertion to the extracellular vesicles
Regular physical activity and exercise training are important tools to improve cardiovascular fitness and reduce mortality. There is growing body of evidence on how high-intensity interval training provides greater health benefits than lower intensity, long-duration training programs.
The cells emit extracellular vesicles of intracellular origin in various sizes. These vesicles are able to transfer various biomolecules (proteins, lipids, nucleic acids, and sugars) between cells, thereby it influences of host cell functions in a receptor-dependent or receptor-independent manner. Preliminary research suggests that extracellular vesicles may be responsible for the systemic effects of exercise by delivering these biomolecules.
In this research, we aimed to investigate and analyse the effect of high-intensity interval training on extracellular vesicles production and its cargo content. Vesicles were isolated from venous blood samples of 12 healthy man. Our goal is to give a definitive answer to the questions: at what time point in sampling, how much and in what size range is the extracellular vesicles are being present?
The molecular effects of the overload-induced hypertrophy
Sirt1 is NAD dependent deacetylase which has many physiological functions in aging metabolism and in gene expression, tumor suppression, oxidative damage protection, etc. In recent years it seems that Sirt1 potentially has an important role in skeletal muscle hypertrophy. In the last few years more and more articles had published showed the role of the Sirt1 in muscle hypertrophy. In this study we would like to elucidate contribution of Sirt1 to the already established molecular mechanisms in muscle hypertrophy.
In this animal model we surgically remove the gastrocnemius and soleus muscles of the rat then the plantaris muscle will take over the role of the other plantar flexors. Due to this constant overload the plantaris muscle largely hypertrophies. In our study we examine the underlying molecular mechanism with a major focus on the protein synthesis, mitochondrial biogenesis and mitophagy markers.
The role of exercise on smooth muscles and myoelectic characteristics of the gastrointestinal system
Regular aerobic exercise can influence the adaption processes in gastrointestinal system, including the composition of the microbiome and the gastrointestinal motility. These processes might be involved in colon cancer, overweight nervous system diseases as well. The exact changes in the transcription profile of the gut cells, moreover the differential gastrointestinal motility induced by training types intensities are not well understood yet.
In this study we are aiming to characterize the motility profile from various sections of the gastrointestinal tract and to detect changes in the smooth muscle electromyography (SEMG) signals due to physical activity. Our novel EMG instrument let us measure the different gastrointestinal segments myoelectric activity.
Our supposition is that high intensity interval training method (HIIT) could modify differently the efficiency of the gastrointestinal motility, as the moderate intensity continuous training (MICT) method. Moreover we think HIIT could accelerate the colon motility, and slow down the small intestine motility what can contribute to the optimal gastrointestinal health and it helps to improve the composition of the microbiome.
The pathology of Alzheimer’s disease in response to exercise and probiotics in transgenic mouse model, the liver in focus.
The gut's microbiome is complex ecosystem what may play an important role even in onset diseases that are usually not associated with the gastrointestinal system. Its already known that the composition of the microbiome is age and diet, but physical activity also affects its characteristics. Alzheimer’s disease is one of the most known neurodegenerative, what in the majority of the cases develops in old age. Regular physical activity and exercise training has a systemic effect and it has the capacity to slow the ageing process, more over number of publications showed connections between the microbiome and brain functions. In this project we are investigating the exercise induced health benefits in the brain and contribution of the liver and microbiome.
The enigma behind the systemic effects of regular exercise: Is it related to VO2max or molecular adaptive pathways?
In this study our goal is to acquire knowledge about the systemic effect of exercise. The duration of the exercise intervention lasted for 6 month. This relative long exercise period can help us to understand how VO2 max increase affects different organ functions, their metabolism and the reproduction capacity on an elderly population (55-65 year). Before and after the 6 month training program organ functions, cognitive capacity, body composition was measured for the participants and blood test was conducted. The exercise protocol contained 40 minutes interval training 3 times a week. We assume that our results will confirm the positive impact of regular training on the organ functions and the alteration of VO2 max level will be the main factor of the adaptation process.
The effect of weight loss on the human microbiome in adult Hungarian national wrestlers.
One of the most difficult tasks in weight-category sports is to get into the right weight category. The psychological and physical effects of weight loss have been studied in several international studies. In our research, we investigate the effect of weight loss on the microbiome composition in adult freestyle and greco-roman elite wrestlers. In this research, body composition analysis, anaerobic capacity measurement and microbiome testing are performed, and the wrestlers keep a nutritional diary. We hypothesize that weight loss has an effect on the composition of the microbiome. Our goal is to identify bacteria in the microbiome whose amount and / or function affect fitness and their presence is associated with lower body fat percentage.
The effect of exercise on the microbiome in human with high BMI.
In the highest weight groups of combat sports, one can often find individuals who can be classified as obese based on their high body mass index. However these athletes are doing serious training almost every day. Our goal in our study is to investigate the microbiomic composition of these athletes and compare it to physically inactive obese persons. We are aiming to understand the effects of exercise in this special group of athletes because their microbiome composition may shed light to the “fit fat” phenomena. We hypothesize that despite the similarity of BMI, the intestinal flora of trained people differs from that of the untrained and obese groups.
Research and development of occlusion training based performance enhancing techniques
One important tasks of the research center include the research and development of new tools and training forms that can be used in elite sports and rehabilitation. To this end, the so-called occlusion training forms, which have been very popular in the last few decades, are being studied at our institute. The occlusion, or “blood flow restriction training”, induces adaptation processes by limiting the venous backflow of the limb performing the exertion. In this study, we look for opportunities that can improve conditional abilities by further developing the classical occlusion method. The classic occlusion method with resistance training, uses venous compression throughout the training and therefore the load level is relatively low, 20-30% of the single repetition maximum (1RM max). In the present research, we test that if the load is increased to optimal 70% of the 1RM max, and at the same time the occlusion treatment is limited to rest time, can it significantly increase exercise physiologic markers compared to control conditions? We expect that, this study will lead us to the development of new training methods that can be successfully applied in elite sports during preparation phase.
Cell physiological changes due to nicotinamide administration and exercise as approached by aging-regulating proteins
Aging can be defined as an age-dependent decrease in the maintenance of homeostasis. As we age, the frequency and severity of dementia and neurodegenerative diseases increase significantly. Research shows that the aging process is accompanied by an increase in the amount of lysine acetylation in proteins. Sirtuin proteins are NAD + dependent histone deacetylating enzymes. Several deacetylase inhibitors have been used to influence nervous system processes, but the effect of sirtuin inhibitors has not been studied. In our research, we administered nicotinamide (NAM), a specific inhibitor of SIRT1. Our study was performed on 4- and 28-month-old female rats (control, trainer, control NAM and trainer NAM groups). Six weeks of treadmill training were applied at a speed of 10 m / min, five times a week, while the duration was gradually increased. Nicotinamide doses was 1% and then decreased to 0.5% in the drinking water of the animals. In addition to physiological parameters, we also tested certain brain functions that examine learning efficiency and memory.
The effect of interval training and probiotics supplementation on the course of Alzheimer's disease in a transgenic mouse model
Alzheimer's disease is affecting more and more people worldwide, with both health and economic implications. It is estimated that the number of people with the disease will triple by 2050, reaching a patient population of 150 million. As the disease progresses, people affected by the disease struggle with memory impairment, speech disorder, and spatial and temporal incoordination. Regular physical exercise has been shown to have a beneficial effect on neurodegenerative diseases. Recently, probiotics are becoming increasingly important for the composition of the intestinal flora and also for brain functions. In our experiment, we demonstrated that regular physical activity and regular use of probiotics help to delay the symptoms characteristic of the disease.
Human muscle biopsy study
In the framework of international scientific cooperation, a gene expression study is being carried out to monitor the molecular changes in human skeletal muscle as a result of physical exercise. In this study muscle biopsy samples were taken from Greek Cypriot volunteers. Subjects were divided into 3 age groups: 20-40 years, 40-60 years, and 60-80 years. In each age group, further subdivisions were made into untrained and trained groups. First biopsy samples were taken before the physical activity and then volunteers were subjected to a single load of exercise followed by repeated biopsies. RNA and protein were extracted from the muscle biopsy samples. From RNA preparations, messenger RNA levels of several selected genes were measured (e.g., several members of the sirtuin family, mitochondrial proteins, DNA repair proteins). Protein samples were quantified using Western blott technique. Gene expression in skeletal muscle of different age groups were analysed based on the obtained data.
For non-human research models a conventional animal facility has been set up in our institute with testing and service areas. In the animal facility to ensure the reproducibility and measurement accuracy animals are kept in controlled environment with 12 hours light-dark cycles.
Applied methods on which research programs are based:
- behavioral science methods, major focus on alertness, learning and memory, emotional behavior, stress sensitivity
- physical condition markers
- swimming exercise and balancing
- vibration as proprioceptive training
- measurement of eating behavior
- effects of a high-fat diet and obesity
- carbohydrate and fat metabolism studies
- alcohol preference, addiction
- hormone measurements
- neuroanatomical techniques