The poly-omics of ageing through individual-based metabolic modelling

Abstract Background Ageing can be classified in two different ways, chronological ageing and biological ageing. While chronological age is a measure of the time that has passed since birth, biological (also known as transcriptomic) ageing is defined by how time and the environment affect an individual in comparison to other individuals of the same chronological age. Recent research studies have shown that transcriptomic age is associated with certain genes, and that each of those genes has an effect size. Using these effect sizes we can calculate the transcriptomic age of an individual from their age-associated gene expression levels. The limitation of this approach is that it does not consider how these changes in gene expression affect the metabolism of individuals and hence their observable cellular phenotype. Results We propose a method based on poly-omic constraint-based models and machine learning in order to further the understanding of transcriptomic ageing. We use normalised CD4 T-cell gene expression data from peripheral blood mononuclear cells in 499 healthy individuals to create individual metabolic models. These models are then combined with a transcriptomic age predictor and chronological age to provide new insights into the differences between transcriptomic and chronological ageing. As a result, we propose a novel metabolic age predictor. Conclusions We show that our poly-omic predictors provide a more detailed analysis of transcriptomic ageing compared to gene-based approaches, and represent a basis for furthering our knowledge of the ageing mechanisms in human cells

Prestress in

Fibres in living cells carry the pre-existing tension (so-called prestress) even without external loading. By changing the prestress, cells are able to control actively their overall mechanical response; it is therefore an important element in cell elasticity. To capture this feature, we propose the hyperelastic model of living tissues composed of balls and springs. The prestress in fibres is maintained due to the assumption of the constant volume of cells (it does not allow the springs to relax). Even if the structure is simple, the determination of reference configuration leads to non-unique solutions and bifurcations

A model of engineering materials inspired by biological tissues

The perfect ability of living tissues to control and adapt their mechanical properties to varying external conditions may be an inspiration for designing engineering materials. An interesting example is the smooth muscle tissue since this "material" is able to change its global mechanical properties considerably by a subtle mechanism within individual muscle cells. Multi-scale continuum models may be useful in designing essentially simpler engineering materials having similar properties. As an illustration we present the model of an incompressible material whose microscopic structure is formed by flexible, soft but incompressible balls connected mutually by linear springs. This simple model, however, shows a nontrivial nonlinear behavior caused by the incompressibility of balls and is very sensitive on some microscopic parameters. It may elucidate the way by which "small" changes in biopolymer networks within individual muscular cells may control the stiffness of the biological tissue, which outlines a way of designing similar engineering materials. The 'balls and springs' material presents also prestress-induced stiffening and allows elucidating a contribution of extracellular fluids into the tissue’s viscous properties

Tilser I. Direct effects of proteasome inhibitor AdaAhx3L3VS on protein and amino acid metabolism in rat skeletal muscle. Physiol Res 54: 541–547

Summary Proteasome inhibitors are novel potential drugs for therapy of many diseases, and their effects are not fully understood. We investigated direct effects of peptide vinylsulfone inhibitor AdaAhx 3 L 3 VS on protein and amino acids metabolism in rat skeletal muscle. Soleus and extensor digitorum longus muscles were incubated in a medium containing 30 µmol/l AdaAhx 3 L 3 VS or no inhibitors. Total proteolysis was determined according to the rates of tyrosine release into the medium during incubation. The rates of leucine oxidation and protein synthesis were evaluated during incubation in medium containing L-[1-14 C]leucine. Amino acid concentrations in the medium were measured using HPLC. AdaAhx 3 L 3 VS decreased tyrosine release into the medium by 21 and 19 %, decreased leucine incorporation into proteins by 22 and 12 %, and increased leucine oxidation by 24 and 19 % in soleus and extensor digitorum longus muscles, respectively. The release of amino acids into the medium was reduced. We conclude that AdaAhx 3 L 3 VS significantly decreased proteolysis and protein synthesis and increased leucine oxidation

Health effects of beer from the angle of free radicals and antioxidants.

Alcohol and mixture of antioxidants belong among the main biologically effective components in beer. The article indicates in a well-arranged from the efficiency of alcohol on organism; the ratio of the favourable and unfavourable effects depends on the amount of its daily consumption. The favourable effect of alcohol consists mainly in the increase of concentration of antiatherogenic high density lipoproteins (HDL), in inhibition of lipoperoxidation and in the antiaggregational incidence on blood platelets. In beer the antioxidants come from malt, less specifically from hops; this is mostly the question of polyphenols. The survey sums up the main physiological effects of these antioxidants; the inhibition of oxidation of low density lipoproteins (LDL), vasodilatation and the antioxidant incidence. As chelators of metals, they hedge the rice of hydroxyle radical by the Fentor reaction. The authors end by summarizing results of their own antioxidant capacity measurement of some sorts of beer.(In Czech, English summary only

Hydrogeology of the deepest underwater cave in the world: Hranice Abyss, Czechia

Little is known about water mixing in deep underwater cave shafts of hypogene karst. The Hranice Abyss (HA) in Czechia is currently the deepest underwater cave in the world. It shares a thermal and CO2-rich water source with an adjacent spa. Based on chemical and isotope composition, water in the HA is a mixture of shallow and thermal groundwaters. The shallow local groundwater is distinctly different from the adjacent Bečva River water in its elemental chemistry and sulfate δ34S values. The thermal water is mixed with 5–10% of modern water, based on tritium content and chlorofluorocarbons. Vertical profiling and deep sampling in the HA showed distinct changes with depth in temperature and TDS. Density-driven flow controls the mixing. In winter, the shallow water of the open HA lake is efficiently cooled; the denser surface water sinks to greater depths, which mixes the water column in the HA. During the summer the shallow water stagnates at the depth of 0–15 m. Periods of stagnation and of accelerated water flow and mixing in the HA perfectly fit with the periodic occurrence of CO2 evasion in the lake and the overall characteristics of the microbial communities, which showed the absence of any functional stratification. Ferric oxyhydroxide precipitation is the major cause for turbidity in the HA. Elevation-specific hydraulic responses of the HA groundwater, caused by the adjacent river’s level pulses, enabled a determination of the points along the river course at which the river is connected to groundwater by karst conduits