Tobias Jung

Tobias Jung
German Institute of Human Nutrition | DIfE · Department of Molecular Toxicology (MTOX)

Doctor of Philosophy

About

86
Publications
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Publications

Publications (86)
Article
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Effects of feeding male rats during spermatogenesis a high‐fat, high‐sucrose and high‐salt diet (HFSSD) over two generations (F0 and F1) on renal outcomes are unknown. Male F0 and F1 rats were fed either control diet (F0CD+F1CD) or HFSSD (F0HD+F1HD). The outcomes were glomerular filtration rate and urinary albumin excretion in F1 and F2 offspring....
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Aging is associated with the development of chronic low-grade systemic inflammation (LGSI) characterized by increased circulating levels of proinflammatory cytokines and acute phase proteins such as C-reactive protein (CRP). Collective evidence suggests that elevated levels of inflammatory mediators such as CRP, interleukin-6 (IL-6), and tumor necr...
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Cardiac remodeling and contractile dysfunction are leading causes in hypertrophy-associated heart failure (HF), increasing with a population’s rising age. A hallmark of aged and diseased hearts is the accumulation of modified proteins caused by an impaired autophagy-lysosomal-pathway. Although, autophagy inducer rapamycin has been described to exer...
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Non-alcoholic fatty liver disease (NAFLD), as a consequence of overnutrition caused by high-calorie diets, results in obesity and disturbed lipid homeostasis leading to hepatic lipid droplet formation. Lipid droplets can impair hepatocellular function; therefore, it is of utmost importance to degrade these cellular structures. This requires the nor...
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Sarcopenia represents a muscle-wasting syndrome characterized by progressive and generalized degenerative loss of skeletal muscle mass, quality, and strength occurring during normal aging. Sarcopenia patients are mainly suffering from the loss in muscle strength and are faced with mobility disorders reducing their quality of life and are, therefore...
Article
Naked mole‐rats express many unusual traits for such a small rodent. Their morphology, social behaviour, physiology, and ageing have been well studied over the past half‐century. Many early findings and speculations about this subterranean species persist in the literature, although some have been repeatedly questioned or refuted. While the popular...
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Overnutrition contributes to insulin resistance, obesity and metabolic stress, initiating a loss of functional beta-cells and diabetes development. Whether these damaging effects are amplified in advanced age is barely investigated. Therefore, New Zealand Obese (NZO) mice, a well-established model for the investigation of human obesity-associated t...
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Scope: Several studies showed that excessive lipid intake can cause hepatic steatosis. To investigate lipotoxicity on cellular level, palmitate (PA) is often used to highly increase lipid droplets (LDs). One way to remove LDs is autophagy, while it is controversially discussed if autophagy is also affected by PA. We aimed to investigate whether PA...
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Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, cultu...
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Adipogenesis is a fundamental process of white adipose tissue function, supporting lipid storage and release, while avoiding its spillover and ectopic accumulation in tissues and organs. During aging adipogenesis is impaired, and among other factors, oxidative stress contributes to this process. Adipogenesis requires functional and dynamic mitochon...
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Measurement and quantification of cardiomyocyte or cardiac contractions as important (patho) physiologic parameters require highly specialized and expensive setups of fully integrated hard- and software that may be very difficult to use and may also depend on highly sophisticated methods of further data evaluation. With MYOCYTER (MC) we present a c...
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The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are...
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The skeletal muscle is a crucial tissue for maintaining whole body homeostasis. Aging seems to have a disruptive effect on skeletal muscle homeostasis including proteostasis. However, how aging specifically impacts slow and fast twitch fiber types remains elusive. Muscle proteostasis is largely maintained by the proteasomal system. Here we characte...
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The ubiquitin-proteasomal-system (UPS) and the autophagy-lysosomal-system (ALS) are both highly susceptible for disturbances leading to the accumulation of cellular damage. A decline of protein degradation during aging results in the formation of oxidatively damaged and aggregated proteins finally, resulting in failure of cellular functionality. Be...
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Large amounts of data from multi-channel, high resolution, fluorescence microscopic images require tools that provide easy, customizable and reproducible high-throughput analysis. The freeware “ImageJ” has become one of the standard tools for scientific image analysis. Since ImageJ offers recording of “macros”, even a complex multi-step process can...
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Aged tissues usually show a decreased regenerative capacity accompanied by a decline in functionality. During aging pancreatic islets also undergo several morphological and metabolic changes. Besides proliferative and regenerative limitations, endocrine cells lose their secretory capacity, contributing to a decline in functional islet mass and a de...
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Metabolic syndrome (MS) is a chronic pathology characterized (amongst others) by dysregulated plasma glucose and high serum triglycerides. One of the central organs affected is the liver, causing increasing fat accumulation and inflammation. To investigate the impact of chronic inflammation and fat accumulation on the main mammalian proteolytic and...
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The white adipose tissue (WAT) is crucial for maintaining metabolism homeostasis by storing lipids and/or by secreting adipokines. A healthy WAT relies on continuous renewal, through a multi-step process called adipogenesis. Upon failure, the risk for lipotoxicity across the organism is higher and insulin resistance can arise in several tissues. A...
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Type 2 diabetes is a chronic metabolic disorder characterized, among other features, by elevated levels of circulatory free fatty acids. Several studies in animal and cellular models indicate that increased accumulation of lipids leads to oxidative and ER stress, mitochondrial dysfunction and alteration of proteostasis, resulting in cellular dysfun...
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The production of reactive species is an inevitable by-product of metabolism and thus, life itself. Since reactive species are able to damage cellular structures, especially proteins, as the most abundant macromolecule of mammalian cells, systems are necessary which regulate and preserve a functional cellular protein pool, in a process termed “prot...
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Aging is accompanied by the accumulation of cellular damage over time in response to stress, lifestyle and environmental factors ultimately leading to age-related diseases and death. Additionally, the number of senescent cells increases with age. Senescence is most likely not a static endpoint, it represents a series of hallmarks including morpholo...
Chapter
Oxidative modification of proteins is an important hallmark of the aging process, leading to cellular dysfunction as well as a decreased cellular viability, tissue failure, and consequently the development of age-related diseases. To avoid the oxidative modification of cellular structures, cells are provided with an antioxidant defense system that...
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Mitochondria have been in the focus of oxidative stress and aging research for decades due to their permanent production of ROS during the oxidative phosphorylation. The hypothesis exists that mitochondria are involved in the formation of lipofuscin, an autofluorescent protein aggregate that accumulates progressively over time in lysosomes of post-...
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Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the...
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Changes in the two main intracellular degradation systems, the Ubiquitin-Proteasome System and the Autophagy-Lysosome pathway (ALP) are widely discussed as a hallmark of the aging process. To follow the age-related behavior of both degradation systems we examined their impact on ferritin, known to be degradable by both. Ferritin H was analyzed in y...
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The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we reveale...
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One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of ox...
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Significance: Since the metabolic syndrome (MS) and pathologies associated with/resulting from metabolic dysregulations became a worldwide spreading and growing problem, the mechanisms mediating the according cellular changes got into a focus of interest. The ubiquitin-proteasomal system (UPS) is the main regulator of both the functional and dysfu...
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Numerous cellular functions rely on an active proteasome allowing degradation of damaged or misfolded proteins. Therefore changes in the proteasomal activity have important physiological consequences. During oxidative stress the production of free radicals can result in the formation of 4-hydroxynonenal (HNE) following lipid peroxidiation. The HNE...
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Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease characterized by insulin resistance and β cell failure leading to elevated blood glucose levels. Hyperglycemia is suggested to be the main cause of diabetic complications, which not only decrease life quality and expectancy, but are also becoming a problem regard...
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In this study, the athermal effects of water-filtered infrared A (wIRA)-irradiation (780-1400 nm) on human dermal fibroblasts were investigated. For this purpose, cells were exposed to wIRA-irradiation (178 mW/cm(2) for 1h), while a sophisticated experimental setup prevented warming of the samples exceeding 0.1 °C. The investigated parameters were...
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Reactive oxygen species (ROS) are formed continuously in the organism even under physiological conditions. If the level of ROS in cells exceeds the cellular defense capacity, components such as RNA/DNA, lipids and proteins are damaged and modified, thus affecting the functionality of organelles as well. Especially proteins are prominent targets of...
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The main machinery responsible for cellular protein maintenance is the ubiquitin-proteasomal system, with its core particle the 20S proteasome. The main task of the system is a fast and efficient degradation of proteins not needed anymore in cellular metabolism. For this aim a complex system of regulators evolved, modifying the function of the 20S...
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Reviews our current understanding of the role of protein oxidation in aging and age-related diseases Protein oxidation is at the core of the aging process. Setting forth a variety of new methods and approaches, this book helps researchers conveniently by exploring the aging process and developing more effective therapies to prevent or treat age-rel...
Chapter
Half Title Wiley Series Title Copyright Contents Introduction to the Wiley Series on Protein and Peptide Science Preface
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In the current literature, the lysosomal system is considered to be involved in the intracellular formation and accumulation of lipofuscin, a highly oxidized and covalently cross-linked aggregate of proteins that fills the lysosomal volume during aging. In contrast, our experimental results presented here suggest that both the autophagosomes and th...
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Considering the widespread application of water-filtered infrared A (wIRA) irradiation in medicine, cosmetics, and wellness, we have conluded that the biological effects of this electromagnetic spectrum, ranging from 780 nm to 1400 nm, have become an important focus of experimental research. Two main effects of wIRA on single cells are discussed: t...
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The ubiquitin-proteasomal system is an essential element of the protein quality control machinery in cells. The central part of this system is the 20S proteasome. The proteasome is a barrel-shaped multienzyme complex, containing several active centers hidden at the inner surface of the hollow cylinder. So, the regulation of the substrate entry towa...
Article
Protein carbonylation is a common feature in cells exposed to oxidants, leading to protein dysfunction and protein aggregates. Actin, which is involved in manifold cellular processes, is a sensitive target protein to this oxidative modification. T-cell proteins have been widely described to be sensitive targets to oxidative modifications. The aim o...
Article
In many recent publications, supposed athermal effects of water-filtered infrared A (wIRA) irradiation are discussed. Those effects are mainly attributed to wavelengths in the range from 780 to 1440 nm, and should not result from warming of cellular water or any aqueous medium surrounding the irradiated sample caused by wIRA absorption. Athermal ef...
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Lipofuscin, a highly oxidized aggregate, consists of covalently cross-linked proteins, lipids, and sugar residues and is one of the major life-span-limiting factors in postmitotic aging cells. An artificial model of this material, showing characteristics and effects comparable to those of the natural form, has turned out to be very useful for in vi...
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Changes in protein turnover are among the dominant metabolic changes during aging. Of special importance is the maintenance of nuclear protein homeostasis to ensure a coordinated cellular metabolism. Therefore, in the nucleus a special PARP-1-mediated mechanism of proteasomal activation exists to ensure a rapid degradation of oxidized nuclear prote...
Article
Tau is the major protein exhibiting intracellular accumulation in Alzheimer disease. The mechanisms leading to its accumulation are not fully understood. It has been proposed that the proteasome is responsible for degrading tau but, since proteasomal inhibitors block both the ubiquitin-dependent 26S proteasome and the ubiqutin-independent 20S prote...
Article
Aging is accompanied by an intracellular accumulation of lipofuscin, a hydrophobic yellow-brownish material that accumulates especially in the lysosomal compartment, where it can be neither degraded nor exocytosed from the cell. The intracellular effects of accumulating lipofuscin are still a subject of speculation. In addition to the demonstrated...
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Since lipofuscin, the so-called “aging pigment”, turned out to play a fundamental role in the aging process, particularly in the postmitotic senescence of muscle or neuronal cells, it became a focus of aging and stress research. During normal aging, lipofuscin accumulates in a nearly linear way, whereas its rate of formation can increase in the fin...
Article
Infrared radiation is a substantial part of the solar energy output reaching the earth surface. Therefore, exposure of humans to infrared radiation is common. However, whether and how infrared (IR) or infrared A acts on human skin cells is still under debate. Recently the generation of reactive oxygen species by water-filtered infrared A (wIRA) irr...
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Solar ultraviolet (UV) A radiation is a well known trigger of signaling responses in human skin fibroblasts. One important consequence of this stress response is the increased expression of matrix metalloproteinase-1 (MMP-1), which causes extracellular protein degradation and thereby contributes to photoaging of human skin. In the present study we...
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Oxidative stress has been widely considered as a key player in the adverse effects of hyperglycaemia to various tissues, including neuronal cells. This study examined the participation of oxidative stress in injurious effects of high glucose on HT22 cells along with the activity of proteasome, a proteolytic system responsible for degradation of oxi...
Article
Rising interest in the mechanism and function of the proteasomes and the ubiquitin system revealed that it is hard to find any aspect of the cellular metabolic network that is not directly or indirectly affected by the degradation system. This includes the cell cycle, the "quality control" of newly synthesized proteins (ERAD), transcription factor...
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Magnetic resonance imaging (MRI) of magnetically labeled stem cells has become a valuable tool in the understanding and evaluation of experimental stem cell-based therapies of degenerative central nervous system disorders. This comprehensive study assesses the impact of magnetic labeling of both human and rodent stem cell-containing populations on...
Article
Aging is accompanied by an accumulation of oxidized proteins and cross-linked modified protein material. The intracellular formation and accumulation of highly oxidized and cross-linked proteins, the so-called lipofuscin, is a typical sign of senescence. However, little is known whether the lipofuscin accumulation during aging is related to environ...
Article
The generation of free radicals and the resulting oxidative modification of cell structures are omnipresent in mammalian cells. This includes the permanent oxidation of proteins leading to the disruption of the protein structure and an impaired functionality. In consequence, these oxidized proteins have to be removed in order to prevent serious met...
Article
Free radicals and other highly reactive particles are a by-product of the cellular metabolism. Those particles are able to induce oxidative damage to cellular structures, resulting in reduced functionality. During evolution, different strategies developed in order to countervail that chronic oxidative stress. One of those strategies is the intracel...
Article
In recent years, there has been increasing evidence that cholesterol plays a role in the pathology of Alzheimer disease. Since hypercholesterolemia was reported to increase the levels of reactive oxygen species and Alzheimer disease has clearly involved an oxidative component, it is possible that hypercholesterolemia is via increased oxidant produc...
Article
One of the highlights of postmitotic aging is the intracellular accumulation of highly oxidized and cross-linked proteins, known as lipofuscin. Lipofuscin is insoluble and not degradable by lysosomal enzymes or the proteasomal system, which is responsible for the recognition and degradation of misfolded and oxidatively damaged proteins. These aggre...
Article
The cellular proteome is in a dynamic state of synthesis and degradation. Degradation of extracellular proteins is mainly mediated non-specifically by the lysosomes or due to released proteases, while the proteolysis of intracellular including nuclear proteins is catalyzed by the ubiquitin-proteasome pathway. Furthermore, the proteasomal system is...