Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.     

Cytotoxic and antimitotic effects of N-containing Monascus metabolites studied using immortalized human kidney epithelial cells

Recently the first Monascus metabolites with a pyridine ring were detected, the monascopyridines A and B. They are formally dehydrogenated derivatives of the red rice pigments rubropunctamine and monascorubramine. Because of their structural similarity, the toxicological effects of these secondary metabolites were studied using immortalized human kidney epithelial cells. The cytotoxicity was determined with the following different endpoint detection methods: metabolic activity, trypan blue exclusion, and electronic cell counting. The compounds led to EC(50) values between 11 and 31 micromol/L but the pigments caused a stronger reduction of the cell viability. Also, the apoptotic potential was examined by measuring caspase 3 activity and detecting apoptotic bodies, but none of the tested compounds induced apoptosis. All four substances caused a rise of the mitotic index to about 9% (100 micromol/L monascopyridine A and B) and 20% (25 micromol/L rubropunctamine and monascorubramine). The significant decrease of the ratio of cells in the ana- and telophase to cells in the prometa- and metaphase proved a stop of the mitosis at the meta- to anaphase control point. The compounds caused mitotic arrest and the formation of structural damages like c-mitosis through interaction with the mitotic spindle. These effects point to an aneuploidy inducing potential, which is linked to cancer formation.     

New Monascus metabolites: structure elucidation and toxicological properties studied with immortalized human kidney epithelial cells

Monascus sp. are used for the production of red yeast rice, which has been applied in Asian food and medicine for centuries. The fungi form several secondary metabolites, among others the monascopyridines A and B. We have now detected two new monascopyridines (named C and D) with similar UV absorption spectra and maxima at 306-307 nm in red rice fermented with M. purpureus. The new monascopyridines have the same chromophores as the already known and differ in a missing gamma-lactone ring only. Monascopyridine C has a hexanoyl side chain, whereas monascopyridine D is the higher homologue with an octanoyl side chain. The toxicological properties of monascopyridines were studied using immortalized human kidney epithelial cells, displaying cytotoxic effects in micromolar concentrations with median effective concentration values between 20.7 and 43.2 micromol/L, depending on the compound and method used. The monascopyridines C and D did not induce apoptosis. However, they caused a rise of the mitotic index from 3.21 +/- 0.27% (control) to maximum 8.14 +/- 0.89% (monascopyridine D) by an accumulation of cells in the metaphase with a simultaneous decrease of cells in the ana- and telophase. Monascopyridine-induced metaphase arrest is caused by a partial or complete loss of the spindle apparatus as indicated by the occurrence of abnormal metaphases and immunological staining of alpha-tubulin. These effects are indicating an aneuploidic potential and therefore the monascopyridines C and D might contribute to tumor formations.     

Augmenting research cooperation in production engineering with data analytics

Understanding how members of a research team cooperate and identifying possible synergies may be crucial for organizational success. Using data-driven approaches, recommender systems may be able to find promising collaborations from publication data. Yet, the outcome of scientific endeavors (i.e. publications) are only produced sparingly in comparison to other forms of data, such as online purchases. In order to facilitate this data in augmenting research cooperation, we suggest to combine data-driven approaches such as text-mining, topic modeling and machine learning with interactive system components in an interactive visual recommendation system. The system leads to an augmented perspective on research cooperation in a network: Interactive visualization analyzes, which cooperation could be intensified due to topical overlap. This allows to reap the benefit of both worlds. First, utilizing the computational power to analyze large bodies of text and, second, utilizing the creative capacity of users to identify suitable collaborations, where machine-learning algorithms may fall short.     

The Adaptive Solar Facade: From concept to prototypes

The Adaptive Solar Facade (ASF) is a modular, highly integrated dynamic building facade.The energetic behavior as well as the architectural expression of the facade can be controlled with high spatio-temporal resolution through individually addressable modules. We present the general design process, the current mechanical design, and simulation results on photovoltaic power production and building energy consumption. We introduce the controller concept and show results on solar tracking as well as user interaction. Lastly, we present our current and planned prototypes.