Ageing represents a main risk factor for several pathologies. Among them, cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) are predominant in the elderly population and often require prolonged use of multiple drugs due to their chronic nature and the high proportion of co-morbidities. Hence, research is constantly looking for novel, effective molecules to treat CVD and T2DM with minimal side effects.
View Article and Find Full Text PDFSenescent cells may have a prominent role in driving inflammation and frailty. The impact of cellular senescence on frailty varies depending on the assessment tool used, as it is influenced by the criteria or items predominantly affected by senescent cells and the varying weights assigned to these items across different health domains. To address this challenge, we undertook a thorough review of all available studies involving gain- or loss-of-function experiments as well as interventions targeting senescent cells, focusing our attention on those studies that examined outcomes based on the individual frailty phenotype criteria or specific items used to calculate two humans (35 and 70 items) and one mouse (31 items) frailty indexes.
View Article and Find Full Text PDFThe homozygous genotype of the Longevity-Associated Variant (LAV) in Bactericidal/Permeability-Increasing Fold-Containing Family B member 4 (BPIFB4) is enriched in long-living individuals of three independent populations and its genetic transfer in C57BL/6J mice showed a delay in frailty progression and improvement of several biomarkers of aging and multiple aspects of health. The C57BL/6J strain is a suitable model for studying therapies aimed at extending healthy aging and longevity due to its relatively short lifespan and the availability of aging biomarkers. Epigenetic clocks based on DNA methylation profiles are reliable molecular biomarkers of aging, while frailty measurement tools are used to evaluate overall health during aging.
View Article and Find Full Text PDFFrailty is an age-related condition characterized by a multisystem functional decline, increased vulnerability to stressors, and adverse health outcomes. Quantifying the degree of frailty in humans and animals is a health measure useful for translational geroscience research. Two frailty measurements, namely the frailty phenotype (FP) and the clinical frailty index (CFI), have been validated in mice and are frequently applied in preclinical research.
View Article and Find Full Text PDFCigarette butts (CBs), one of the most common litter items found on beaches, represent a still unexplored environmental hazard. This study aimed at a multidisciplinary characterization of their toxicological risks on marine organisms integrating chemical analyses of released compounds with a wide panel of biological responses, such as ecotoxicological bioassays on species of different trophic positions, molecular responses in an ex vivo model (Precision-Cut Tissue Slices, PCTS of mussels digestive glands), bioavailability and cellular biomarkers in mussels exposed to CBs in laboratory experiments. Trace metals, aliphatic and polycyclic aromatic hydrocarbons, nicotine and cotinine were released in artificial seawater after 24 h which determined a significant inhibition of bacterial bioluminescence, oyster embryo development and growth in different algal species.
View Article and Find Full Text PDFTetrodotoxins (TTXs), potent neurotoxins, have become an increasing concern in Europe in recent decades, especially because of their presence in mollusks. The European Food Safety Authority published a Scientific Opinion setting a recommended threshold for TTX in mollusks of 44 µg equivalent kg and calling all member states to contribute to an effort to gather data in order to produce a more exhaustive risk assessment. The objective of this work was to assess TTX levels in wild and farmed mussels () harvested in 2018-2019 along the coastal area of the Marche region in the Central Adriatic Sea (Italy).
View Article and Find Full Text PDFOcean-warming and acidification jeopardize Antarctic marine species, adapted to cold and constant conditions and naturally exposed to high pro-oxidant pressures and cadmium (Cd) bioavailability. The aim of this study was to investigate if projected temperature increase and pH reduction may affect the accumulation and the effects of Cd in the rockcod . Organisms were exposed for 14 days to six scenarios, combining environmental or increased temperature (-1 °C, +1 °C) and control or reduced pH (8.
View Article and Find Full Text PDFThe striped venus (Chamelea gallina) is an important economic resource in the Mediterranean Basin; this species has exhibited a strong quantitative decline in the Adriatic Sea. The aim of this work was to provide a comprehensive view of the biological status of C. gallina to elucidate the bioecological characteristics and genetic diversity of wild populations.
View Article and Find Full Text PDFAnthropogenic inputs of carbon dioxide in the atmosphere are driving ocean warming and acidification. The potential threat represented by these changes for marine species could be amplified in coastal areas, characterized by higher levels of pollutants. In addition, temperate organisms may exhibit a different seasonal tolerance to stressors influenced by fluctuations of environmental and physiological factors.
View Article and Find Full Text PDFAzaspiracids (AZAs) are marine biotoxins including a variety of analogues. Recently, novel AZAs produced by the Mediterranean dinoflagellate were discovered (AZA-54, AZA-55, 3-epi-AZA-7, AZA-56, AZA-57 and AZA-58) and their biological effects have not been investigated yet. This study aimed to identify the biological responses (biomarkers) induced in mussels after the bioaccumulation of AZAs from .
View Article and Find Full Text PDFThe precision-cut tissue slices (PCTS) represent a largely used biological model in mammalian research. This ex vivo approach offers the main advantages of in vitro systems, while maintaining the natural architecture of the tissue. The use of PCTS in toxicological research has been proposed for investigating the cellular effects of xenobiotics or bioactive compounds mostly in mammalian models.
View Article and Find Full Text PDFAlthough the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)-a bioactive component of the green alga that has invaded the entire Mediterranean basin-is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays.
View Article and Find Full Text PDFDespite the key importance of Nrf2-Keap1 in regulating antioxidant system in vertebrates, this system is still poorly investigated in marine species. The present study focused on the Antarctic silverfish Pleuragramma antarctica which, during the final phases of embryo development in platelet ice, is challenged by a sudden enhancement of environmental oxidative conditions associated to ice melting. Partial coding sequences were identified for Nrf2, its repressor Keap1 and for typical Nrf2-target antioxidant genes, like catalase, glutathione peroxidase isoform 1 and Cu/Zn-dependent superoxide dismutase.
View Article and Find Full Text PDFOxidative stress biomarkers are widely used in marine ecotoxicology. Environmental pollutants enhance intracellular formation of oxyradicals through several mechanisms, but complex oxidative interactions occur in response to chemical mixtures. Metabolism of individual classes of pollutants can be influenced by a sophisticated network of prooxidant relationships, reciprocal and cascade effects, changes of redox-sensitive signaling proteins, and transcription factors.
View Article and Find Full Text PDFAntioxidant defences play a central role in cell protection against a wide variety of environmental stressors, their variations being thus frequently studied to reveal oxidative stress conditions in fish. The Nrf2-Keap1 pathway is among the main mechanisms of transcriptional regulation in mammalians, but its involvement in modulation of antioxidant system of aquatic organisms is still largely unexplored. The present study focused on the identification of Nrf2 and Keap1 in the European eel Anguilla anguilla using liver slices as an in vitro model during an oxidative challenge.
View Article and Find Full Text PDFThe antioxidant system of marine organisms consists of low molecular weight scavengers and antioxidant enzymes which interact in a sophisticated network. Environmental pollutants can unbalance this system through closely related mechanisms, indirect relationships and cascade effects acting from pre-transcriptional to catalytic levels. Chemically-mediated pathways have the potential to greatly enhance intracellular formation of reactive oxygen species (ROS); at the same time, excessive levels of oxyradicals down-regulate xenobiotics metabolism, with important environmental implications for organisms exposed to chemical mixtures.
View Article and Find Full Text PDFAntioxidant and biotransformation pathways are widely studied in marine organisms exposed to environmental stressors. However, mechanisms of responses and links between different intracellular levels are not always easy to elucidate and conflicting results are frequently observed between molecular and enzymatic data. In this study, transcriptional and catalytic responses of antioxidant and biotransformation parameters were analyzed after a 4-week exposure of a marine invertebrate, Mytilus galloprovincialis, to chemical mixtures from low polluted and highly polluted sediments.
View Article and Find Full Text PDFThe cytochrome P450 pathway and antioxidant responses are known for their responsiveness to environmental pollutants and are frequently used as biomarkers at the transcriptional, translational and catalytic levels. Although molecular responses are often assumed to reflect similar changes in enzyme function, several factors can influence intracellular effects, including mRNA stability and protein turnover, signal sensing and transduction, post-translational modifications of proteins, and multiple mode of action of chemicals in complex mixtures. The aim of this study was to use experimental data for a general discussion on the importance of mechanisms modulating transcriptional and catalytic responses of these pathways, and the resulting implications for environmental monitoring.
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