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Due to the successful implementation of vaccination strategies early-life morbidity and mortality due to infectious disease has been reduced dramatically. Vaccines against tetanus and diphtheria are among the most frequently used vaccines worldwide, but various studies in different European countries have shown that protection against tetanus and particularly against diphtheria is unsatisfactory in adults and older persons. In this study we analyzed tetanus- and diphtheria-specific antibody concentrations in 2100 adults of different age from 6 selected European countries (Austria, Belgium, Germany, Greece, Italy, Poland) in order to investigate differences in the level of protection against tetanus and diphtheria across Europe. Our data reveal that tetanus- and diphtheria-specific antibody concentrations vary greatly between countries, which is also reflected in the percentage of persons with antibody concentrations below the protective level (0.1 IU/ml), which ranged from 2 to 31% percent for tetanus and 28–63% for diphtheria. In most countries, tetanus- and diphtheria-specific antibody concentrations decrease with age. This phenomenon is more pronounced in countries with generally low antibody levels, such as Italy, Poland and Greece. Interestingly, tetanus-specific antibody concentrations are generally higher in males than in females, which is probably due to vaccination during their military service or more frequent booster vaccinations after injuries, whereas no gender-related differences were found for diphtheria-specific antibodies. In conclusion, our study demonstrates that the European population is not fully protected against tetanus and diphtheria. Measures to improve protection should include a life-long perspective on vaccination, more education to increase awareness of and compliance with vaccination guidelines, and a harmonization of recommendations and incentives across Europe.

Increasing cellular damage during the aging process is considered to be one factor limiting the lifespan of organisms. Besides the DNA and lipids, proteins are frequent targets of non-enzymatic modifications by reactive substances including oxidants and glycating agents. Non-enzymatic protein modifications may alter the protein structure often leading to impaired functionality. Although proteolytic systems ensure the removal of modified proteins, the activity of these proteases was shown to decline during the aging process. The additional age-related increase of reactive compounds as a result of impaired antioxidant systems leads to the accumulation of damaged proteins and the formation of protein aggregates. Both, non-enzymatic modified proteins and protein aggregates impair cellular functions and tissue properties by a variety of mechanisms. This is increasingly important in aging and age-related diseases. In this review, we will give an overview on oxidation and glycation of proteins and the function of modified proteins in aggregate formation. Furthermore, their effects as well as their role in aging and age-related diseases will be highlighted.

Increasing cellular damage during the aging process is considered to be one factor limiting the lifespan of organisms. Besides the DNA and lipids, proteins are frequent targets of non-enzymatic modifications by reactive substances including oxidants and glycating agents. Non-enzymatic protein modifications may alter the protein structure often leading to impaired functionality. Although proteolytic systems ensure the removal of modified proteins, the activity of these proteases was shown to decline during the aging process. The additional age-related increase of reactive compounds as a result of impaired antioxidant systems leads to the accumulation of damaged proteins and the formation of protein aggregates. Both, non-enzymatic modified proteins and protein aggregates impair cellular functions and tissue properties by a variety of mechanisms. This is increasingly important in aging and age-related diseases. In this review, we will give an overview on oxidation and glycation of proteins and the function of modified proteins in aggregate formation. Furthermore, their effects as well as their role in aging and age-related diseases will be highlighted.

In physiological conditions intracellular radical formation is mostly due to mitochondrial activity. This is in contrast to clinical and pathophysiological situations, where the oxidant formation is additionally driven by xenobiotics and inflammation. Oxidative damage accumulation in macromolecules especially in proteins has been considered as a cause of cellular damage and pathology impairing the clinical outcome of patients. However, up to now strategies to measure oxidative stress in clinical settings are limited. A lot of parameters and techniques are available for the determination of oxidized proteins in biological systems. Unfortunately, most of them are no reliable markers in clinical settings due to their unknown clinical relevance or the lack in clinical feasibility. Major problems are the sample availability, sample stability and cost-, time- and man-power intensive methods. The present review focuses on the measurement of protein oxidation products from a chemical, biological, and medical point of view.

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 largely responsible for the removal of unfolded and oxidatively damaged proteins. Taking into account the role of ubiquitin and proteasome system in protein metabolism, studies of its spatial organization within the cell are of great importance. For the understanding of cellular, including nuclear, protein maintenance the distribution of the proteasomes in both the nucleus and the cytosol and their response upon oxidative stress is of great interest. Although, the functional diversity of the cells is ensured by the three dimensional organization of the nucleus, nuclear proteins are also prone to oxidation and have to be removed from the cellular environment by the nuclear proteasome. Interestingly, nuclear proteins are partly degraded within the nucleus, whereas some are exported from the nucleus to the cytosol. Proteasomes are transported unidirectionally from the cytoplasm to the nucleus with a possible countervail during mitosis. This review is focused largely on the specifics of cellular proteasome distribution and on nuclear protein maintenance under physiological and oxidative stress conditions.