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- Antioxidant, mineralogenic and osteogenic activities of Spartina alterniflora and Salicornia fragilis extracts rich in polyphenolsPublication . Roberto, Vania Palma; Surget, Gwladys; Le Lann, Klervi; Mira, Sara; Tarasco, Marco; Guérard, Fabienne; Poupart, Nathalie; Laizé, Vincent; Stiger-Pouvreau, Valérie; Cancela, M. LeonorOsteoporosis is an aging-related disease and a worldwide health issue. Current therapeutics have failed to reduce the prevalence of osteoporosis in the human population, thus the discovery of compounds with bone anabolic properties that could be the basis of next generation drugs is a priority. Marine plants contain a wide range of bioactive compounds and the presence of osteoactive phytochemicals was investigated in two halophytes collected in Brittany (France): the invasive Spartina alterniflora and the native Salicornia fragilis. Two semi-purified fractions, prepared through liquid-liquid extraction, were assessed for phenolic and flavonoid contents, and for the presence of antioxidant, mineralogenic and osteogenic bioactivities. Ethyl acetate fraction (EAF) wasrich in phenolic compounds and exhibited the highest antioxidant activity. While S. fragilis EAF only triggered a weak proliferative effect in vitro, S. alterniflora EAF potently induced extracellular matrix mineralization (7-fold at 250µg/mL). A strong osteogenic effect was also observed in vivo using zebrafish operculum assay (2.5-fold at 10µg/mL in 9-dpf larvae). Results indicate that polyphenol rich EAF of S. alterniflora has both antioxidant and bone anabolic activities. As an invasive species, this marine plant may represent a sustainable source of molecules for therapeutic applications in bone disorders.
- Measuring healthy ageing: current and future toolsPublication . Silva, Nádia; Rajado, Ana Teresa; Esteves, Filipa; Brito, David V.C.; Apolónio, Joana; Roberto, Vânia; Binnie, Alexandra; Araújo, Inês Maria; Nóbrega, Clévio; Bragança, José; Castelo-Branco, PedroHuman ageing is a complex, multifactorial process characterised by physiological damage, increased risk of age-related diseases and inevitable functional deterioration. As the population of the world grows older, placing significant strain on social and healthcare resources, there is a growing need to identify reliable and easy-to-employ markers of healthy ageing for early detection of ageing trajectories and disease risk. Such markers would allow for the targeted implementation of strategies or treatments that can lessen suffering, disability, and dependence in old age. In this review, we summarise the healthy ageing scores reported in the literature, with a focus on the past 5 years, and compare and contrast the variables employed. The use of approaches to determine biological age, molecular biomarkers, ageing trajectories, and multi-omics ageing scores are reviewed. We conclude that the ideal healthy ageing score is multisystemic and able to encompass all of the potential alterations associated with ageing. It should also be longitudinal and able to accurately predict ageing complications at an early stage in order to maximize the chances of successful early intervention.
- Reprogramming iPSCs to study age-related diseases: models, therapeutics, and clinical trialsPublication . Esteves, Filipa; Brito, David; Rajado, Ana Teresa; Silva, Nádia; Apolónio, Joana; Roberto, Vania Palma; Araújo, Inês Maria; Nóbrega, Clévio; Castelo-Branco, Pedro; Bragança, José; P. Andrade, Raquel; M. Calado, Sofia; Faleiro, L; Matos, Carlos A; Marques, Nuno; Marreiros, Ana; Nzwalo, Hipólito; Pais, Sandra; Palmeirim, Isabel; S, Simão; Joaquim, Natércia; Miranda, Rui; Pêgas, António; Raposo, Daniela Marques; Sardo, AnaThe unprecedented rise in life expectancy observed in the last decades is leading to a global increase in the ageing population, and age-associated diseases became an increasing societal, economic, and medical burden. This has boosted major efforts in the scientific and medical research communities to develop and improve therapies to delay ageing and age-associated functional decline and diseases, and to expand health span. The establishment of induced pluripotent stem cells (iPSCs) by reprogramming human somatic cells has revolutionised the modelling and understanding of human diseases. iPSCs have a major advantage relative to other human pluripotent stem cells as their obtention does not require the destruction of embryos like embryonic stem cells do, and do not have a limited proliferation or differentiation potential as adult stem cells. Besides, iPSCs can be generated from somatic cells from healthy individuals or patients, which makes iPSC technology a promising approach to model and decipher the mechanisms underlying the ageing process and age-associated diseases, study drug effects, and develop new therapeutic approaches. This review discusses the advances made in the last decade using iPSC technology to study the most common age-associated diseases, including age-related macular degeneration (AMD), neurodegenerative and cardiovascular diseases, brain stroke, cancer, diabetes, and osteoarthritis.
- DNA Methylation of PI3K/AKT pathway-related genes predicts outcome in patients with pancreatic cancer: a comprehensive bioinformatics-based studyPublication . Faleiro, Inês; Roberto, Vania Palma; Demirkol Canli, Secil; Fraunhoffer, Nicolas A.; Iovanna, Juan; Gure, Ali Osmay; Link, Wolfgang; Castelo-Branco, PedroPancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database (n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4, SFN, ITGA2, and PIK3R1 methylation levels could be independent prognostic indicators of patients’ survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients’ clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.
- Establishment of an induced pluripotent cell line (ABCRIi001-A) from an elderly female for ageing researchPublication . Esteves, Filipa; Vilhena Catarino Brito, David; Rajado, Ana Teresa; Silva, Nádia; Apolónio, Joana; Roberto, Vânia; Andrade, Raquel; Calado, Sofia; Faleiro, Maria Leonor; Albuquerque Andrade de Matos, Carlos Adriano; Marques, Nuno; Marreiros, Ana; Nzwalo, Hipólito; Pais, Sandra; Palmeirim, Isabel; Simãoa, Sónia; Joaquim, Natércia; Miranda, Rui; Pêgas, António; Raposo, Daniela Marques; Sardo, Ana; Araújo, Inês; Nóbrega, Clévio; Castelo-Branco, Pedro; Bragança, JoséHuman induced pluripotent stem cells (hiPSCs) hold promises to model and understand human diseases, including those associated with ageing. Here, we describe ABCRIi001-A, a hiPSC line generated from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female enrolled in a study for development of an ageing score (ALFA Score). PBMCs were reprogrammed using three Sendai virus-based reprogramming vectors (hKOS, hc-Myc, and hKlf4). ABCRIi001-A showed normal morphology and karyotype, viral clearance, absence of genomic aberrations, and their pluripotency was confirmed by expression of pluripotency-related markers and their ability to differentiate into the three germ layers. ABCRIi001-A is valuable for ageing-related studies.
- Fish microbiome modulation and convenient storage of aquafeeds when supplemented with Vitamin K1Publication . Acosta, Marcos; Quiroz, Eduardo; Tovar-Ramírez, Dariel; Roberto, Vania Palma; Dias, Jorge; Gavaia, Paulo; Fernández, IgnacioVitamin K (VK), and particularly phylloquinone (VK1), is an essential micronutrient whose stability in aquafeeds has not been extensively evaluated. Losing stability can lead to nutritional deficiency, which is known to hamper fish development and physiology. Gut microbiota also plays a key role in host health through the interaction with several biological processes. The present study evaluated the best storing conditions of aquafeeds when supplemented in VK1 and intestinal microbiota modulation in Senegalese sole (Solea senegalensis) juveniles. Aquafeeds with a high level of VK1 supplementation required storage at −20 ◦C for short-term (up to 7 days) and at −80 ◦C for long-term (up to three months) to ensure optimal preservation. Furthermore, gut bacterial communities of Senegalese sole specimens fed with a commercial feed supplemented with VK1 showed a better-balanced population of microorganisms in the intestine, which might improve Senegalese sole health during the ongrowing phase. These results provide the practical guidelines for the proper storing of aquafeeds in the industry when supplemented with VK1 and highlight the potential benefits of dietary VK1 supplementation for a balanced intestinal microbiota and overall fish health.