Cell Stress during Development and Disease - Special Issue, Review article Balancing DNA repair to prevent ageing and cancer

DNA damage is a constant stressor to the cell. Persistent damage to the DNA over time results in an increased risk of mutation and an accumulation of mutations with age. Loss of efficient DNA damage repair can lead to accelerated ageing phenotypes or an increased cancer risk, and the trade-off between cancer susceptibility and longevity is often driven by the cell's response to DNA damage. High levels of mutations in DNA repair mutants often leads to excessive cell death and stem cell exhaustion which may promote premature ageing. Stem cells themselves have distinct characteristics that enable them to retain low mutation rates. However, when mutations do arise, stem cell clonal expansion can also contribute to age-related tissue dysfunction as well as heightened cancer risk. In this review, we will highlight increasing DNA damage and mutation accumulation as hallmarks common to both ageing and cancer. We will propose that anti-ageing interventions might be cancer preventative and discuss the mechanisms through which they may act

Revegetation of ski runs in Serbia: Case studies of Mts. Stara Planina and Divčibare

Revegetation is the most sustainable method of soil stabilization at ski runs. In order to establish a stable plant community, it is recommended to use native species. However, non-native species are most often used. In this paper the revegetation of ski runs at two ski resorts is investigated: Divčibare and Stara Planina. Seven species were used for the revegetation of the ski run at the Divčibare ski resort of which six species were native. Six species were used for the revegetation of the Stara Planina ski resort, of which two species were native. It was established that the plant species used in the seed mixtures were suitable for erosion control at the investigated ski resorts

Agephagy – Adapting Autophagy for Health During Aging

Autophagy is a major cellular recycling process that delivers cellular material and entire organelles to lysosomes for degradation, in a selective or non-selective manner. This process is essential for the maintenance of cellular energy levels, components, and metabolites, as well as the elimination of cellular molecular damage, thereby playing an important role in numerous cellular activities. An important function of autophagy is to enable survival under starvation conditions and other stresses. The majority of factors implicated in aging are modifiable through the process of autophagy, including the accumulation of oxidative damage and loss of proteostasis, genomic instability and epigenetic alteration. These primary causes of damage could lead to mitochondrial dysfunction, deregulation of nutrient sensing pathways and cellular senescence, finally causing a variety of aging phenotypes. Remarkably, advances in the biology of aging have revealed that aging is a malleable process: a mild decrease in signaling through nutrient-sensing pathways can improve health and extend lifespan in all model organisms tested. Consequently, autophagy is implicated in both aging and age-related disease. Enhancement of the autophagy process is a common characteristic of all principal, evolutionary conserved anti-aging interventions, including dietary restriction, as well as inhibition of target of rapamycin (TOR) and insulin/IGF-1 signaling (IIS). As an emerging and critical process in aging, this review will highlight how autophagy can be modulated for health improvement

Hantavirus infections in forestry workers

Bjedov, L., Margaletić, J., Vucelja, M., Medved, M.M., Matijević, I., Krajinović, L.C., Markotic, A

A versatile, automated and high-throughput drug screening platform for zebrafish embryos

Zebrafish provide a unique opportunity for drug screening in living animals, with the fast developing, transparent embryos allowing for relatively high-throughput, microscopy-based screens. However, the limited availability of rapid, flexible imaging and analysis platforms has limited the use of zebrafish in drug screens. We have developed an easy-to-use, customisable automated screening procedure suitable for high-throughput phenotype-based screens of live zebrafish. We utilised the WiScan® Hermes High Content Imaging System to rapidly acquire brightfield and fluorescent images of embryos, and the WiSoft® Athena Zebrafish Application for analysis, which harnesses an Artificial Intelligence-driven algorithm to automatically detect fish in brightfield images, identify anatomical structures, partition the animal into regions, and exclusively select the desired side-oriented fish. Our initial validation combined structural analysis with fluorescence images to enumerate GFP-tagged haematopoietic stem and progenitor cells in the tails of embryos, which correlated with manual counts. We further validated this system to assess the effects of genetic mutations and x-ray irradiation in high content using a wide range of assays. Further, we performed simultaneous analysis of multiple cell types using dual fluorophores in high throughput. In summary, we demonstrate a broadly applicable and rapidly customisable platform for high-content screening in zebrafish

NONTRIVIAL VARIATIONS OF MORPHO-ANATOMICAL LEAF TRAITS IN NATURAL SOUTH-EASTERN POPULATIONS OF VACCINIUM SPECIES FROM CENTRAL BALKANS

Morpho-anatomical characteristics of Vaccinium myrtillus, V. uliginosum and V. vitis-idaea leaves from several sites of the Central Balkans were examined. The aim of this study was to investigate for the first time morpho-anatomical leaf traits of these species in the studied populations and to identify traits that follow a specific trend along the gradients of climate factors. Leaf traits that discriminate Vaccinium species were as follows: Depth of the adaxial cuticule (AdC), thickness of the palisade tissue (PT), thickness of the spongy tissue (ST), height of the abaxial epidermal cells (AbE), height of the abaxial cuticule (AbC) and leaf thickness (LT). Populations of V. myrtillus were characterized by the smallest, and populations of V. vitis-idaea by the highest values for AdC, PT, ST, AbE and LT. Additionally, AbC was significantly larger for V. uliginosum in comparison to two other species. On the basis of morpho-anatomical traits, intraspecific variability of the studied species was explored by Principal Component Analysis (PCA), Cluster Analysis (CA) and Analysis of Variance (ANOVA). CA based on 10 morpho-anatomical traits showed that populations of V. myrtillus and V. uliginosum that grew at lower altitudes (characterized by higher mean annual temperature) are more similar to each other. Especially V. myrtillus was responsive to the elevational gradient and exhibited the highest plasticity in morpho-anatomical leaf traits. Populations of V. vitis-idaea had a different pattern of differentiation along the elevational gradient. CA showed that the populations at the lowest and at the highest altitudes were more similar according to the morpho-anatomical leaf traits, meaning that evergreen leaves were more resistant to environmental conditions. © Polish Academy of Sciences and Jagiellonian University, Cracow 2021

Autophagy in healthy aging and disease

Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

Increased fidelity of protein synthesis extends lifespan

Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging