Running projects | Finished projects | Animal facility

Running projects

Developing epigenetic based biomarkers for biological age and physical performance

This research primarily investigates the impact of exercise on biological aging, with a particular focus on DNA methylation patterns. Through a combination of human and animal studies, we aim to elucidate the epigenetic mechanisms by which exercise promotes healthy aging, prevents age-related diseases, and reduces functional decline.

Our research initiative include: The role of exercise in regulating gene expression, the impact of exercise on DNA methylation pattern, the effects of exercise on health outcomes and on the ageing process. By advancing our understanding of the molecular basis of exercise, we hope to develop novel biomarkers and exercise strategies, for promoting health and longevity.

The Long-Term Effects of Lactate Intervention and High-Intensity Interval Training (HIIT) on Brain Function in Aging Mice

Lactate, a metabolic product of exercise, has recently been recognized for its potential role in enhancing brain function and neuroplasticity, particularly in the context of aging. Neuroplasticity refers to the brain's ability to form new connections, which is crucial for maintaining cognitive health and combating age-related neurodegenerative diseases.

This research aims to explore the long-term effects of lactate intervention and high-intensity interval training (HIIT) on the brain function of aging mice. Our goal was to assess how lactate supplementation and exercise impact key molecular pathways in the brain, including biomarkers of neuroplasticity such as VEGF and BDNF, and other pathways related to mitochondrial function and metabolic processes.

By isolating brain tissue and blood samples from the aging mice, we evaluated changes in neuroplasticity markers, mitochondrial biogenesis, and angiogenesis. Behavioral tests such as open-field, novel object recognition, and passive avoidance tests were also conducted to measure cognitive improvements. The findings of this study could provide new insights into the potential of lactate as a therapeutic agent to mitigate age-related cognitive decline and its possible application in treating neurodegenerative conditions.

The Impact of Long-Term Iron Supplementation on Mitochondrial Function and Exercise Performance in Rats

Iron is an essential micronutrient that plays a key role in numerous biological processes, including energy metabolism and oxygen transport. While previous studies have suggested that iron supplementation can improve exercise performance, particularly by enhancing oxygen delivery through its role in hemoglobin, the underlying mechanisms are not fully understood. Recent research has indicated that iron may also positively affect mitochondrial function, which could be another crucial factor in improving endurance and physical performance.

This study aimed to investigate whether the improvements in exercise performance resulting from iron supplementation are associated with changes in mitochondrial function. Specifically, we explored the effects of long-term iron supplementation, combined with vitamin B6, on VO2 max, mitochondrial biogenesis, and energy production in rats.

Our study indicated that iron supplementation, in combination with vitamin B6, may enhance exercise performance by improving mitochondrial function, providing empirical evidences on how micronutrients contribute to endurance capacity. These findings could have implications for sports performance and addressing conditions related to mitochondrial dysfunction.

Consecutive Skeletal Muscle PGC-1α Overexpression: A Double-Edged Sword for Mitochondrial Health in Aging Mice

Aging is accompanied by a decline in both skeletal muscle and brain function, with mitochondrial dysfunction being a key contributor to this deterioration. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a vital regulator of mitochondrial biogenesis and function, and its overexpression in skeletal muscle has been shown to mimic the beneficial effects of exercise in young mice. However, the impact of PGC-1α overexpression on aging muscle and its influence on brain health remains poorly understood.

Our findings suggest that while the overexpression of PGC-1α preserves mitochondrial health in skeletal muscle, it does not protect against mitochondrial dysfunction in the hippocampus. In fact, muscular PGC-1α overexpression appears to exacerbate age-related mitochondrial deficits in the brain, likely due to increased oxidative stress and inflammation. These results highlight a dual effect of PGC-1α overexpression: it supports skeletal muscle health but may have negative consequences for hippocampal function in aging. The results of this research could pave the way for developing targeted interventions to preserve muscle function without compromising brain health in the aging population.

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 signaling through the delivery of various biomolecules.

In our research, we aimed to investigate the effect of long-term exercise on the content of extracellular vesicles of varying sizes circulating in human blood. Blood samples were collected from senior rowers at the 2019 World Rowing Masters Championships at Lake Velence and from untrained individuals.

By isolating extracellular vesicles from the collected blood samples and analyzing their biomolecular content, we may gain a better understanding of the signaling pathways that could be responsible for the systemic effects of exercise.

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 and 12 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 (50-70 year). Before and after the 6 and 12 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.

Exploring the Molecular Features of Mitochondrial DNA in Elite Hungarian Athletes

Despite the crucial role of mitochondrial DNA (mtDNA) in cellular energy production, our understanding of its molecular characteristics and mechanisms remains limited. One area of interest is the mitochondrial displacement loop (D-loop), a unique triple-stranded DNA region, unlike the canonical double-helix structure, formed by the stable incorporation of a short third strand known as 7S DNA. Another important feature is mtDNA polymorphism, where variations in base pairs between individuals can result in differences in the function of encoded proteins or specific DNA regions. Additionally, cytosine methylation, a process in which specific enzymes add a methyl group to cytosine bases, may influence gene expression and mitochondrial function.

We are currently investigating the relationship between these three key molecular features—D-loop, polymorphisms, and cytosine methylation—in Hungary's top athletes, including Olympic champions. By exploring these molecular mechanisms in elite athletes, we aim to uncover how these features contribute to mitochondrial biology and potentially influence athletic performance.

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.

Finished projects

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 examined 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.

Our research found that voluntary exercise increased the number of caveolae in the smooth muscle of the intestine and boosted the relative abundance of Bifidobacteria in the gut microbiome, which was linked to higher Akt levels in the intestine. These findings suggest that voluntary exercise has widespread effects on the body, and the connection between intestinal Akt and the microbiome could play a key role in the body’s adaptive response to exercise.

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 investigated the exercise induced health benefits in the brain and contribution of the liver and microbiome.

Research and development of occlusion training based performance enhancing techniques

One of the important tasks of the research center is the research and development of new tools and training methods that can be used in elite sports and rehabilitation. To this end, the so-called occlusion training methods, which have gained popularity in recent decades, are being studied at our institute. Occlusion, or “blood flow restriction training,” induces adaptation processes by limiting the venous backflow from the limb performing the exertion. In this study, we explore opportunities to improve physical abilities by further developing the classical occlusion method. The classic occlusion method, used with resistance training, applies venous compression throughout the training, keeping the load level relatively low at 20-30% of the one-repetition maximum (1RM).

In the present research, we employed a setup where the load was increased to an optimal 70% of the 1RM, while the occlusion treatment was applied only during rest periods. We demonstrated that muscle-specific microRNAs, known as myoMIRs, are involved in the differential adaptation to occlusion training. Our setup may provide a high-load alternative to the classic continuous occlusion method for athletes, optimizing mechanical and metabolic/hemodynamic stress.

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.

Animal facility

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