Percorrer por autor "Lema-Arranz, Carlota"
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- Lifestyle, environment and other major determinants of frailty in older adults: a population-based study from the UK BiobankPublication . Hemadeh, Ali; Lema-Arranz, Carlota; Bonassi, Stefano; Buscarini, Leonardo; Infarinato, Francesco; Romano, Paola; Finti, Alessia; Marinozzi, Franco; Bini, Fabiano; Fernández-Bertólez, Natalia; Teixeira, João Paulo; Lorenzo-López, Laura; Valdiglesias, Vanessa; Laffon, BlancaFrailty is a geriatric multidimensional syndrome characterized by a loss of physiologic reserves and disproportionate vulnerability to external stressors and associated with increased risk of multiple negative health outcomes. Since frailty can be prevented, controlled, and even reverted in its early stages, identifying the main factors involved in its development is crucial to implement preventive and/or restorative interventions. The aim of this study was to assess the impact of a broad range of parameters, including host factors, lifestyle, diet, and environmental and occupational conditions, on the development of frailty in later life. A cross-sectional study was conducted on 221,896 individuals aged 60 and over classified as non-frail (119,332, 53.8%), pre-frail (93,180, 42.0%), and frail (9384, 4.2%) according to the frailty phenotype. Using principal component analysis and machine learning to streamline the data, significant associations were found between frailty risk and air quality, diet, smoking, working conditions, and heavy alcohol consumption. Early-life factors, including breastfed as a baby and maternal smoking around birth, also emerged as predictors of frailty, which was further characterized by clinical indicators like polypharmacy, levels of C-reactive protein and other biomarkers of inflammageing. This study provided robust and original evidence on the association between a large battery of potential risk factors, from early to later stages of life, and the occurrence of frailty in older age. These results will contribute to the development of effective prevention strategies and facilitate the early detection of individuals at high risk of developing frailty.
- Relationship between DNA damage measured by the comet-assay and cognitive functionPublication . Lorenzo-López, Laura; Lema-Arranz, Carlota; Fernández-Bertólez, Natalia; Costa, Solange; Costa, Carla; Teixeira, João Paulo; Pásaro, Eduardo; Valdiglesias, Vanessa; Laffon, BlancaRecent studies exploring the relationship between DNA damage measured by the comet assay (single-cell gel electrophoresis) and cognitive function in both animal models and humans are reviewed and summarized. This manuscript provides an overview of studies exploring cognitive dysfunction related to DNA damage due to biological ageing process, cancer treatment, adverse environmental or occupational exposures, and prenatal genotoxic exposure. The review confirms the potential of comet assay to further explore the link between DNA damage, as indicative of genomic instability, and cognitive impairment in different research and clinical areas. Analysed studies support, in fact, the significant relationship between DNA damage and cognitive impairment, mainly affecting attention, working memory and executive functions. These cognitive domains are crucial to daily functioning and occupational performance, with important clinical implications. Although evidence support the relationship between DNA damage measured by the comet assay and cognitive function in different settings, further longitudinal research is needed to disentangle the temporal relationship between them over time, and to explore the potential of comet assay-detected DNA lesions to predict response to interventions.
- Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA DamagePublication . Valdiglesias, Vanessa; Fernández-Bertólez, Natalia; Lema-Arranz, Carlota; Rodríguez-Fernández, Raquel; Pásaro, Eduardo; Reis, Ana Teresa; Teixeira, João Paulo; Costa, Carla; Laffon, BlancaMetal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use.
- Suitability of salivary leucocytes to assess DNA repair ability in human biomonitoring studies by the challenge-comet assayPublication . Fernández-Bertólez, Natalia; Lema-Arranz, Carlota; Fraga, Sónia; Teixeira, João Paulo; Pásaro, Eduardo; Lorenzo-López, Laura; Valdiglesias, Vanessa; Laffon, BlancaThe challenge-comet assay is a simple but effective approach that provides a quantitative and functional determination of DNA repair ability, and allows to monitor the kinetics of repair process. Peripheral blood mononuclear cells (PBMC) are the cells most frequently employed in human biomonitoring studies using the challenge-comet assay, but having a validated alternative of non-invasive biomatrix would be highly convenient for certain population groups and circumstances. The objective of this study was to validate the use of salivary leucocytes in the challenge-comet assay. Leucocytes were isolated from saliva samples and challenged (either in fresh or after cryopreservation) with three genotoxic agents acting by different action mechanisms: bleomycin, methyl methanesulfonate, and ultraviolet radiation. Comet assay was performed just after treatment and at other three additional time points, in order to study repair kinetics. The results obtained demonstrated that saliva leucocytes were as suitable as PBMC for assessing DNA damage of different nature that was efficiently repaired over the evaluated time points, even after 5 months of cryopreservation (after a 24 h stimulation with PHA). Furthermore, a new parameter to determine the efficacy of the repair process, independent of the initial amount of damage induced, is proposed, and recommendations to perform the challenge-comet assay with salivary leucocytes depending on the type of DNA repair to be assessed are suggested. Validation studies are needed to verify whether the method is reproducible and results reliable and comparable among laboratories and studies.