Measuring healthy ageing: current and future tools.

Human 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.

The TERT hypermethylated oncologic region predicts recurrence and survival in pancreatic cancer.

AIM: We explore the biomarker potential of the TERT hypermethylated oncologic region (THOR) in pancreatic cancer. MATERIALS & METHODS: We assessed the methylation status of THOR using the cancer genome atlas data on the cohort of pancreatic cancer (n = 193 patients). RESULTS: THOR was significantly hypermethylated in pancreatic tumor tissue when compared with the normal tissue used as control (p < 0.0001). Also, THOR hypermethylation could distinguish early stage I disease from normal tissue and was associated with worse prognosis. DISCUSSION:  We found that THOR is hypermethylated in pancreatic tumor tissue when compared with normal tissue and that THOR methylation correlates with TERT expression in tumor samples. CONCLUSION: Our preliminary findings support the diagnostic and prognostic values of THOR in pancreatic cancer.

Reprogramming iPSCs to study age-related diseases: Models, therapeutics, and clinical trials.

The 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.

Fish Microbiome Modulation and Convenient Storage of Aquafeeds When Supplemented with Vitamin K1.

Vitamin K (VK) is a fat-soluble vitamin necessary for fish metabolism and health. VK stability as dietary component during aquafeed storage and its potential effect on intestinal microbiome in fish have not yet been completely elucidated. The convenient storage conditions of aquafeeds when supplemented with phylloquinone (VK1), as well as its potential effects on the gut microbiota of Senegalese sole (Solea senegalensis) juveniles, have been explored. Experimental feeds were formulated to contain 0, 250 and 1250 mg kg-1 of VK1 and were stored at different temperatures (4, -20 or -80 °C). VK stability was superior at -20 °C for short-term (7 days) storage, while storing at -80 °C was best suited for long-term storage (up to 3 months). A comparison of bacterial communities from Senegalese sole fed diets containing 0 or 1250 mg kg-1 of VK1 showed that VK1 supplementation decreased the abundance of the Vibrio, Pseudoalteromonas, and Rhodobacterace families. All these microorganisms were previously associated with poor health status in aquatic organisms. These results contribute not only to a greater understanding of the physiological effects of vitamin K, particularly through fish intestinal microbiome, but also establish practical guidelines in the industry for proper aquafeed storage when supplemented with VK1.

Identification of colorectal cancer associated biomarkers: an integrated analysis of miRNA expression.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. This complex disease still holds severe problems concerning diagnosis due to the high invasiveness nature of colonoscopy and the low accuracy of the alternative diagnostic methods. Additionally, patient heterogeneity even within the same stage is not properly reflected in the current stratification system. This scenario highlights the need for new biomarkers to improve non-invasive screenings and clinical management of patients. MicroRNAs (miRNAs) have emerged as good candidate biomarkers in cancer as they are stable molecules, easily measurable and detected in body fluids thus allowing for non-invasive diagnosis and/or prognosis. In this study, we performed an integrated analysis first using 4 different datasets (discovery cohorts) to identify miRNAs associated with colorectal cancer development, unveil their role in this disease by identifying putative targets and regulatory networks and investigate their ability to serve as biomarkers. We have identified 26 differentially expressed miRNAs which interact with frequently deregulated genes known to participate in commonly altered pathways in colorectal cancer. Most of these miRNAs have high diagnostic power, and their prognostic potential is evidenced by panels of 5 miRNAs able to predict the outcome of stage II and III colorectal cancer patients. Notably, 8 miRNAs were validated in three additional independent cohorts (validation cohorts) including a plasma cohort thus reinforcing the value of miRNAs as non-invasive biomarkers.

DNA Methylation of PI3K/AKT Pathway-Related Genes Predicts Outcome in Patients with Pancreatic Cancer: A Comprehensive Bioinformatics-Based Study.

Pancreatic 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.

Evidences for a New Role of miR-214 in Chondrogenesis.

miR-214 is known to play a role in mammalian skeletal development through inhibition of osteogenesis and stimulation of osteoclastogenesis, but data regarding other vertebrates, as well as a possible role in chondrogenesis, remain unknown. Here, we show that miR-214 expression is detected in bone and cartilage of zebrafish skeleton, and is downregulated during murine ATDC5 chondrocyte differentiation. Additionally, we observed a conservation of the transcriptional regulation of miR-214 primary transcript Dnm3os in vertebrates, being regulated by Ets1 in ATDC5 chondrogenic cells. Moreover, overexpression of miR-214 in vitro and in vivo mitigated chondrocyte differentiation probably by targeting activating transcription factor 4 (Atf4). Indeed, miR-214 overexpression in vivo hampered cranial cartilage formation of zebrafish and coincided with downregulation of atf4 and of the key chondrogenic players sox9 and col2a1. We show that miR-214 overexpression exerts a negative role in chondrogenesis by impacting on chondrocyte differentiation possibly through conserved mechanisms.