Browsing by Subject "Aging"
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Publication Analysis of aging-related changes and influencing factors on the metabolome of beef(2023) Bischof, Greta; Gibis, MonikaAging of beef is necessary to improve its flavor and tenderness. There are two most common aging types, dry-aging and wet-aging. Dry-aged beef is often associated with a higher eating quality than wet-aged beef. The term “dry-aged beef” is not legally defined, so authentication methods are needed to protect the consumers from food fraud. During beef aging, the metabolome of beef changes due to the postmortem metabolism. This dissertation focuses on the aging method as a postmortem process and the resulting changes in the metabolome. As a hypothesis of this study, it was postulated that the detection of these metabolic changes due to aging of beef is feasible by 1H NMR spectroscopy and based on these measurements the evaluation of an authentication model for the aging method of beef is possible. In order to test this hypothesis, a sample preparation and measurement method was developed and based on this, potential influencing factors such as sampling position in muscle, breed and sex were investigated on the metabolome of fresh and aged beef. In the first part of this thesis, the sample preparation and the 1H NMR measurement method were developed. In the sample preparation, the polar fraction of the metabolome was extracted from 200 mg of beef, allowing 24 samples to be prepared in parallel. The sample preparation and the measurement method were validated, and the first aged beef samples were analyzed to check if the aging-related changes in the metabolome could be detected by this method. In the second part of this thesis, the sampling position in the muscle were analyzed for changes or differences in the metabolome due to its location in the muscle. The results showed that the metabolome changes along the length of the M. longissimus thoracis et lumborum, but the influence of the aging type and aging time was more pronounced in the metabolome of beef. The comparison of the surface and the inner part of wet-aged and dry-aged beef showed that the metabolome of dry-aged beef differed greatly between the surface and the inner part, despite the exclusion of the moisture content by freeze-drying and the low microbial load. There were only slight differences between the surface and the inner part for wet-aged beef, which could be due to the influence of microbiota and their metabolites. Therefore, the sampling location in the M. longissimus thoracis et lumborum was determined as precisely as possible for the further studies. The muscles were cut into ten pieces from cranial to caudal and dry-aged or wet-aged for 0, 7, 14, 21, and 28 days, in duplicates. The third part of this thesis focuses on the potential influencing factors such as breed and sex of the animals. Fresh and aged beef samples from three cattle types (heifer, cow, and young bull) and two different breeds (‘Fleckvieh’ and ‘Schwarzbunt’) were analyzed by targeted and non-targeted 1H NMR spectroscopy. Both factors were shown to influence the metabolome of fresh and aged beef. Therefore, these factors had to be included in the authentication model based on both targeted and non-targeted model. The calculation of the authentication model was the main part of this thesis and showed a good prediction of cattle type, breed, aging time and aging type of beef. The authentication model was based on the combination of multiple models of PLS-R and PLS-DA. The model for predicting the cattle type showed an accuracy of 99 %, and the models for predicting the breed depending on the cattle type showed an accuracy of 100 %. Aging time could be predicted with an error of 2.28 days. The statistical models for aging type were separated by aging time based on the determination of aging time. The model for predicting the aging type of 28-day aged samples had an accuracy of 99 %. The other statistical models for predicting aging type were additionally separated by cattle type and breed, and their accuracy ranged from 90 % to 100 %. In conclusion, an authentication model to determine the cattle type, breed, aging time and aging type of beef was developed in this dissertation. Therefore, it is possible to authenticate beef samples using a single 1H NMR spectrum. In future studies, it would be useful to extend this authentication model to other samples of other breeds and influencing factors.Publication Association of Torquetenovirus Viremia with physical frailty and cognitive impairment in three independent European cohorts(2023) Giacconi, Robertina; Laffon, Blanca; Costa, Solange; Teixeira-Gomes, Armanda; Maggi, Fabrizio; Macera, Lisa; Spezia, Pietro Giorgio; Piacenza, Francesco; Bürkle, Alexander; Moreno-Villanueva, María; Bonassi, Stefano; Valdiglesias, Vanessa; Teixeira, Joao Paulo; Dollé, Martijn E.T.; Rietman, M. Liset; Jansen, Eugène; Grune, Tilman; Gonos, Efstathios S.; Franceschi, Claudio; Capri, Miriam; Weinberger, Birgit; Sikora, Ewa; Stuetz, Wolfgang; Toussaint, Olivier; Debacq-Chainiaux, Florence; Hervonen, Antti; Hurme, Mikko; Slagboom, P. Eline; Schön, Christiane; Bernhardt, Jürgen; Breusing, Nicolle; Pásaro, Eduardo; Maseda, Ana; Lorenzo-López, Laura; Millán-Calenti, José Carlos; Provinciali, Mauro; Malavolta, MarcoIntroduction: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. Methods: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). Results: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06–10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14–5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000–1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. Conclusions: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV’s clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.Publication Cognitive alterations in old mice are associated with intestinal barrier dysfunction and induced toll-like receptor 2 and 4 signaling in different brain regions(2023) Brandt, Annette; Kromm, Franziska; Hernández-Arriaga, Angélica; Martínez Sánchez, Inés; Bozkir, Haktan Övül; Staltner, Raphaela; Baumann, Anja; Camarinha-Silva, Amélia; Heijtz, Rochellys Diaz; Bergheim, InaEmerging evidence implicate the ‘microbiota–gut–brain axis’ in cognitive aging and neuroinflammation; however, underlying mechanisms still remain to be elucidated. Here, we assessed if potential alterations in intestinal barrier function and microbiota composition as well as levels of two key pattern-recognition receptors namely Toll-like receptor (TLR) 2 and TLR4, in blood and different brain regions, and depending signaling cascades are paralleling aging associated alterations of cognition in healthy aging mice. Cognitive function was assessed in the Y-maze and intestinal and brain tissue and blood were collected in young (4 months old) and old (24 months old) male C57BL/6 mice to determine intestinal microbiota composition by Illumina amplicon sequencing, the concentration of TLR2 and TLR4 ligands in plasma and brain tissue as well as to determine markers of intestinal barrier function, senescence and TLR2 and TLR4 signaling. Cognitive function was significantly impaired in old mice. Also, in old mice, intestinal microbiota composition was significantly altered, while the relative abundance of Gram-negative or Gram-positive bacteria in the small and large intestines at different ages was not altered. Moreover, intestinal barrier function was impaired in small intestine of old mice, and the levels of TLR2 and TLR4 ligands were also significantly higher in both portal and peripheral blood. Furthermore, levels of TLR2 and TLR4 ligands, and downstream markers of TLR signaling were higher in the hippocampal and prefrontal cortex of old mice compared to young animals. Taken together, our results suggest that even in ‘healthy’ aging, cognitive function is impaired in mice going along with an increased intestinal translocation of TLR ligands and alterations of TLR signaling in several brain regions.Publication Der Einfluss von Ölgehalt und Fettsäuremuster auf die Lagerfähigkeit von Saatgut(2007) Ghiasvand Ghiasi, Kambiz; Kruse, MichaelSeed storage with the objective of maintaining the quality for the later sowing is a constant challenge, not only in gene banks but also in agriculture, forestry and horticulture. In 1980 ELLIS and ROBERTS established ?The improved seed viability equation? for the prediction of the storability of seeds. With this equation the loss-of-germination-curve can be computed as a function of the initial seed germination, the storage temperature and the seed moisture content for each species. However, with oil-rich seeds the equation very often misses its aim. With this seeds, the variety and lot specific oil content considerably determines water activity and aging rate. Therefore the objective of the present work was to describe the influence of oil content on the aging behavior of seeds of the oil crops during storage quantitatively, to integrate this influence in the most reasonable way into the viability equation and to improve accuracy of its prediction. The investigation was carried out with storage experiments under controlled conditions in the laboratory at higher temperatures and running times between a few days and six months. First it was examined, whether the usually determined oil content of the entire seed is an informative parameter for water activity in the embryo axis. Experiments with sunflowers with an oil content between 28 and 48 % showed that oil-rich seeds need an about 1 % higher seed moisture content than seeds with lower oil content to have the same water activity in the embryonic axis. The storage of these seeds as well as the seeds of rape with oil contents between 39 and 50 % and flax with oil contents between 36 and 43 % showed that the loss of germination is more consistent with uniform water activity than with uniform seed moisture content. This has not been taken into account in the previous viability equation, so that its prediction contains systematic errors. Therefore extensive storage experiments were carried out with altogether 28 seed lots of rape, sunflower, flax and corn with different moisture contents and a uniform temperature of 45°C. Only for few of the stored lots the prediction of the seed viability equation was found to be correct. To include the oil content into the seed viability equation eight different suggestions were compiled. These were applied in three nonlinear regression models with different restrictions to the results of the storage experiments. The first model permitted the species specific determination of the weighing factors (constants) for the seed viability equation. The second model only allowed to determine the weighing factors for the absolute term and the seed moisture content specifically. Oil content was provided however with a species-nonspecific weighing factor. In the third model all weighing factors were species-nonspecific determined. All eight suggestions achieved better estimations for the aging rate in the species-specific models than the previous viability equation. Where this could be examined statistically, the improvements were significant. The same was found for the models with species-nonspecific weighting factors for the oil content. However, not all suggestions led to a converging result of the regression analysis. All examined species-nonspecific models did not improve the adjustment compared to the previous viability equation. The suggestions were then validated with a new and independent dataset with a storage temperature of seeds of 32°C. It was shown that the change of the temperature reduced the accuracy of the estimations of the nonlinear regression models. The new suggestions nevertheless corresponded better to the observed results than the previous viability equation. Based on these results a suggestion was then selected for the extension of the viability equation by ELLIS and ROBERT, which does not introduce a new weighing factor to the equation as the weighing factor might potentially contribute to a decrease of the precision of a prediction due to its standard error. Finally it was examined whether the fatty acid composition before storage in addition to the oil content affects the aging rate and whether the change of the fatty acid composition is directly connected to the loss of germination during storage. Only with rape, significant relations between the proportion of the fatty acid 14:0, 18:0, 20:0, 22:0 and the aging rate of the seed lots were determined. A uniform change of the fatty acid composition of all examined species could not be observed. Therefore this characteristic could not contribute to the further improvement of the prediction accuracy of the seed viability equation. To summarize, a suggestion to include the oil content into the viability equation was designed that clearly improves the accuracy of the prediction of the viability equation for oil-rich seeds and that contributes to a more appropriate and efficient storage of seeds.Publication The effect of aging in the murine gut microbiome(2020) Hernández Arriaga, Angélica; Camarinha-Silva, AméliaAging is characterized by several physiological changes. During the lifespan, the biological systems from the body of humans and other animals remain dynamic. Throughout the early stages of life, the microbiome develops into a complex ecosystem with thousands of species. Variations related to diet, environmental changes, medications affect the diversity and composition of the microbiota through the lifespan. Some old individuals with higher incidence of chronic diseases have a loss of the stability of the microbiome and an imbalance occurs between the different colonizers of the gut, also named dysbiosis. One of the most distinctive changes occurring with age is the prevalent low grade inflammation, which is named inflamm-aging. This not only changes the microbial composition of the GIT but also affects the permeability. Murine models are well established and help us to understand the complex dynamics between the host and the microbial communities inhabiting the gastrointestinal tract. These models allow us to analyze microbial communities from tissue and mucosa, from all sections of the gut, which is limited in humans. Methods standardization is an important topic in microbiome research. In chapter 2 it was compared the efficiency of two sample methods, cotton swab and tissue biopsy, in characterizing the mouth microbiota. In recent years, the mouth microbiome is being seen as a diagnostic tool for not only oral diseases but also systemic diseases. As physiological changes occur with aging, the microbiome from the mouth is affected and there is an increase of pathogens present in the oral surfaces. In murine models, cotton swab is a common tool used for sampling the microbiome of the oral cavity. In our study, we observed similar microbial community structure using both methodologies. However, the species Streptococcus danieliae, Moraxella osloensis, and some unclassified members of Streptococcus were affected by the different sampling procedures. In this trial, we included mice at two different ages, 2 months old being considered young and 15 months old considered middle aged mice. We observed changes in the genera Actinobacillus, Neisseria, Staphylococcus, and Streptococcus related to the age of the animal and the sampling type. These results showed the importance of sampling standardization in microbiome research and that age has a strong effect on the microbial ecology of the oral cavity. In chapter 3, it was studied the bacterial communities from duodenum and colon of mice at 2, 15, 24 and 30 months of age in combination with the results of the expression levels of antimicrobial peptides in small intestine and markers of intestinal barrier function. Besides, in this chapter were also assessed the indices of liver damage, inflammation and expression levels of lipopolysaccharide binding protein (Lbp) as well as of toll-like receptors (Tlr) 1-9 in liver tissues. At 24 and 30 months of age there was an increase in inflammation, they developed fibrosis and the levels of endotoxin in plasma were higher. Regarding changes in the microbiome, the duodenum had more changes than the colon related to age. Allobacullum, Bifidobacterium, Olsenella, Corynebacterium were the genera that differed statistically in the duodenum through the murine lifespan. Fewer changes were observed in the colon, as Allobaculum was the only genus that showed differences between young and old mice. Additionaly, it was analyzed the impact of aging in the active microbial communities of mouth, duodenum and colon at 2, 9, 15, 24 and 30 months of age (chapter 4). Changes were observed at every age and different taxonomical levels, with a greater shift at 15 months of age. This is related to the age of the mice, as at middle age systemic changes related to the aging process start to occur. At old ages, there was an increment of the pathobiontic species Helicobacter hepaticus and Helicobacter ganmani in the duodenum and colon. The oral, duodenal and colonic microbial communities are important pieces of information that can be related to the health status of the host. Research that focuses on assessing the changes in the different niches and not only in the feces, gives a broader overview of the microbial community of the host.Publication Uncovering the relationship between selenium status, age, health, and dietary habits: Insights from a large population study including nonagenarian offspring from the MARK-AGE project(2023) Giacconi, Robertina; Piacenza, Francesco; Aversano, Valentina; Zampieri, Michele; Bürkle, Alexander; Villanueva, María Moreno; Dollé, Martijn E.T.; Jansen, Eugène; Grune, Tilman; Gonos, Efstathios S.; Franceschi, Claudio; Capri, Miriam; Weinberger, Birgit; Sikora, Ewa; Toussaint, Olivier; Debacq-Chainiaux, Florence; Stuetz, Wolfgang; Slagboom, Pieternella Eline; Bernhardt, Jürgen; Fernández-Sánchez, Maria Luisa; Provinciali, Mauro; Malavolta, MarcoAn inadequate selenium (Se) status can accelerate the aging process, increasing the vulnerability to age-related diseases. The study aimed to investigate plasma Se and Se species in a large population, including 2200 older adults from the general population (RASIG), 514 nonagenarian offspring (GO), and 293 GO Spouses (SGO). Plasma Se levels in women exhibit an inverted U-shaped pattern, increasing with age until the post-menopausal period and then declining. Conversely, men exhibit a linear decline in plasma Se levels with age. Subjects from Finland had the highest plasma Se values, while those from Poland had the lowest ones. Plasma Se was influenced by fish and vitamin consumption, but there were no significant differences between RASIG, GO, and SGO. Plasma Se was positively associated with albumin, HDL, total cholesterol, fibrinogen, and triglycerides and negatively associated with homocysteine. Fractionation analysis showed that Se distribution among plasma selenoproteins is affected by age, glucometabolic and inflammatory factors, and being GO or SGO. These findings show that sex-specific, nutritional, and inflammatory factors play a crucial role in the regulation of Se plasma levels throughout the aging process and that the shared environment of GO and SGO plays a role in their distinctive Se fractionation.Publication Walnut oil reduces Aβ levels and increases neurite length in a cellular model of early Alzheimer disease(2022) Esselun, Carsten; Dieter, Fabian; Sus, Nadine; Frank, Jan; Eckert, Gunter P.Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ1–40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.