Search Results (1,229)

Immunosenescence, the age-related decline in immune function, is a complex biological process with profound implications for health and longevity. This phenomenon, characterized by alterations in both innate and adaptive immunity, increases susceptibility to infections, reduces vaccine efficacy, and contributes to the development of age-related diseases. At the cellular level, immunosenescence manifests as decreased production of naive T and B cells, accumulation of memory and senescent cells, thymic involution, and dysregulated cytokine production. Recent advances in molecular biology have shed light on the underlying mechanisms of immunosenescence, including telomere attrition, epigenetic alterations, mitochondrial dysfunction, and changes in key signaling pathways such as NF-κB and mTOR. These molecular changes lead to functional impairments in various immune cell types, altering their proliferative capacity, differentiation, and effector functions. Emerging research suggests that lifestyle factors may modulate the rate and extent of immunosenescence at both cellular and molecular levels. Physical activity, nutrition, stress management, and sleep patterns have been shown to influence immune cell function, inflammatory markers, and oxidative stress in older adults. This review provides a comprehensive analysis of the molecular and cellular mechanisms underlying immunosenescence and explores how lifestyle interventions may impact these processes. We will examine the current understanding of immunosenescence at the genomic, epigenomic, and proteomic levels, and discuss how various lifestyle factors can potentially mitigate or partially reverse aspects of immune aging. By integrating recent findings from immunology, gerontology, and molecular biology, we aim to elucidate the intricate interplay between lifestyle and immune aging at the molecular level, potentially informing future strategies for maintaining immune competence in aging populations. Full article

Background: Runs of homozygosity (ROHs) and heterozygosity (ROHets) serve for the identification of genomic regions as candidates of selection, local adaptation, and population history. Methods: The present study aimed to comprehensively explore the ROH and ROHet patterns and hotspots in Greek native dairy goats, Eghoria and Skopelos, genotyped with the Illumina Goat SNP50 BeadChip. SNP and functional enrichment analyses were conducted to further characterize hotspots and the candidate genes located within these genomic regions. Genetic relationships between and within breeds and inbreeding coefficients were also evaluated. Results: Clear genetic differentiation and diversified management practices were depicted between the two native populations. The ROH and ROHet average genome coverage for Skopelos (65.35 and 35 Mb) and Eghoria (47.64 and 43 Mb) indicated differences in mainland and insular goats, with Skopelos showing more long ROH fragments, reflecting its geographic isolation and small population size. An ROH hotspot (CHR12: 43.59–44.61 Mb) detected in the Skopelos population has been also reported across European goats and co-localizes with a selection signal detected in the Egyptian Barki goats and sheep adapted to hot–arid conditions. A novel ROH hotspot (CHR18: 60.12–61.81 Mb), shared among the Greek breeds, harbors candidate genes enriched in biosynthesis, metabolism, and immune response. Two well-conserved ROHet islands were detected in Greek goats on chromosomes 1 and 18, with genes participating in development and embryogenesis. The Eghoria population showed the highest number of ROHet islands, potentially reflecting its adaptability to diverse environments. Conclusions: These findings offer new insights into the environmental adaptation and artificial selection in Greek goats and could be utilized in future breeding strategies for sustainable goat farming. Full article

DNA methylation is an essential epigenetic modification that plays a crucial role in regulating gene expression and maintaining genomic stability. With the advancement in sequencing technology, methylation studies have provided valuable insights into the diagnosis of rare diseases through the various identification of episignatures, epivariation, epioutliers, and allele-specific methylation. However, current methylation studies are not without limitations. This mini-review explores the current understanding of DNA methylation in rare diseases, highlighting the key mechanisms and diagnostic potential, and emphasizing the need for advanced methodologies and integrative approaches to enhance the understanding of disease progression and design more personable treatment for patients, given the nature of rare diseases. Full article

Plants are increasingly exposed to stress-induced factors, including heavy metals. Zinc, although it is a microelement, at high concentrations can be phytotoxic to plants by limiting their growth and development. The presented research confirmed the inhibition effect of Zn on morphological and physiological parameters in barley plants. However, the effect was Zn dose dependent (50 µM, 100 µM, and 200 µM), as well as part of the plants (above ground or roots). To mitigate the negative effects of Zn, plants were sprayed with 0.1% silicon. Silicon was proven to have a positive effect on mitigating the inhibitory effects of Zn-induced stress. In most cases, an increase in both morphological (length, elongation, fresh and dry weights, and weather content) and physiological (relative chlorophyll content and fluorescence) parameters was observed. This occurrence was dependent on the Zn dose. Epigenetic analyses confirmed differences in the DNA methylation level, both between plants subjected to stress at different strengths (50 µM, 100 µM, and 200 µM Zn) and between plants sprayed with Si or not. The differences indicate that silicon affects the epigenome of barley plants, thereby modifying the response of plants to stress factors. This modification may be the basis for plants to acquire resistance as “epigenetic memory”. Full article

DNA methylation (DNAm) regulates gene expression and genomic imprinting. This study aimed to investigate the effect of gastrointestinal (GI) nematode infection on host DNAm. Helminth-free Holstein steers were either infected with Ostertagia ostertagi (the brown stomach worm) or given tap water only as a control. Animals were euthanized 30 days post-infection, and tissues were collected at necropsy. We conducted epigenome-wide profiling using a mammalian methylation array to explore the impact of infection on methylation patterns in the mucosa from abomasal fundus (FUN), pylorus (PYL), draining lymph nodes (dLNs), and the duodenum (DUO). The analysis covered 31,107 cattle CpGs of 5082 genes and revealed infection-driven, tissue-specific, differential methylation patterns. A total of 389 shared and 2770 tissue-specific, differentially methylated positions (DMPs) were identified in dLN and FUN, particularly in genes associated with immune responses. The shared DMPs were found in 263 genes, many of which are involved in immune responses. Furthermore, 282, 244, 52, and 24 differentially methylated regions (DMRs) were observed in dLN, FUN, PYL, and DUO, respectively. More hypomethylated DMRs were detected in dLN and FUN, while more hypermethylated DMRs were found in PYL and DUO. Genes carrying DMPs and DMRs and enriched pathways relating to immune functions/responses were detected in infected animals, indicating a link between DNA methylation and the infection. The data may implicate a crucial role of DNAm in regulating the nature/strength of host immunity to infection and contribute to a deeper understanding of the epigenetic regulatory landscape in cattle infected by GI nematodes. Full article

Although venous thromboembolism (VTE) is the third most common cardiovascular disease, and the risk of VTE increases sharply with advancing age, approximately 40% of VTE cases are currently classified as unprovoked, highlighting the importance of risk factor research. While chronological aging is associated with the risk of VTE, the association with biological aging remains unclear. Biological aging is highly complex, influenced by several dysregulated cellular and biochemical mechanisms. In the last decade, advancements in omics methodologies provided insights into the molecular complexity of biological aging. Techniques such as high-throughput genomics, epigenomics, transcriptomics, proteomics, and metabolomics analyses identified and quantified numerous epigenetic markers, transcripts, proteins, and metabolites. These methods have also revealed the molecular alterations organisms undergo as they age. Despite the progress, there is still a lack of consensus regarding the methods for assessing and validating these biomarkers, and their application lacks standardization. This review gives an overview of biomarkers of biological aging, including telomere length, and their potential role for VTE. Furthermore, we critically examine the advantages and disadvantages of the proposed methods and discuss possible future directions for investigating biological aging in VTE. Full article

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Understanding the metabolic diversities among cancer cells and their surrounding environments is therefore essential in unravelling the complexities of leukaemia and improving therapeutic strategies. Here, we describe the currently available methodologies and approaches to addressing the dynamic heterogeneity of leukaemia progression. In the second section, we focus on metabolic leukaemic vulnerabilities in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Lastly, we provide a comprehensive overview of the most interesting clinical trials designed to target these metabolic dependencies, highlighting their potential to advance therapeutic strategies in leukaemia treatment. The integration of multi-omics data for cancer identification with the metabolic states of tumour cells will enable a comprehensive “micro-to-macro” approach for the refinement of clinical practices and delivery of personalised therapies. Full article

Addressing the consequences of exposure to endocrine-disrupting chemicals (EDCs) demands thorough research and elucidation of the mechanism by which EDCs negatively impact women and lead to breast cancer (BC). Endocrine disruptors can affect major pathways through various means, including histone modifications, the erroneous expression of microRNA (miRNA), DNA methylation, and epigenetic modifications. However, it is still uncertain if the epigenetic modifications triggered by EDCs can help predict negative outcomes. Consequently, it is important to understand how different endocrine disrupters or signals interact with epigenetic modifications and regulate signalling mechanisms. This study proposes that the epigenome may be negatively impacted by several EDCs, such as cadmium, arsenic, lead, bisphenol A, phthalates, polychlorinated biphenyls and parabens, organochlorine, and dioxins. Further, this study also examines the impact of EDCs on lifestyle variables. In breast cancer research, it is essential to consider the potential impacts of EDC exposure and comprehend how EDCs function in tissues. Full article

Since their discovery, corticosteroids have been widely used in the treatment of several diseases, including asthma, acute lymphoblastic leukemia, chronic obstructive pulmonary disease, and many other conditions. However, it has been noted that some patients develop undesired side effects or even fail to respond to treatment. The reasons behind this have not yet been fully elucidated. This poses a significant challenge to effective treatment that needs to be addressed urgently. Recent genomic, transcriptomic, and other omics-based approximations have begun to shed light into the genetic factors influencing interindividual variability in corticosteroid efficacy and its side effects. Here, we comprehensively revise the recent literature on corticosteroid response in various critical and chronic diseases, with a focus on omics approaches, and highlight existing knowledge gaps where further investigation is urgently needed. Full article

Chronic kidney disease (CKD) is a major worldwide health concern because of its progressive nature and complex biology. Traditional diagnostic and therapeutic approaches usually fail to account for disease heterogeneity, resulting in low efficacy. Precision medicine offers a novel approach to studying kidney disease by combining omics technologies such as genomics, transcriptomics, proteomics, metabolomics, and epigenomics. By identifying discrete disease subtypes, molecular biomarkers, and therapeutic targets, these technologies pave the way for personalized treatment approaches. Multi-omics integration has enhanced our understanding of CKD by revealing intricate molecular linkages and pathways that contribute to treatment resistance and disease progression. While pharmacogenomics offers insights into expected responses to personalized treatments, single-cell and spatial transcriptomics can be utilized to investigate biological heterogeneity. Despite significant development, challenges persist, including data integration concerns, high costs, and ethical quandaries. Standardized data protocols, collaborative data-sharing frameworks, and advanced computational tools such as machine learning and causal inference models are required to address these challenges. With the advancement of omics technology, nephrology may benefit from improved diagnostic accuracy, risk assessment, and personalized care. By overcoming these barriers, precision medicine has the potential to develop novel techniques for improving patient outcomes in kidney disease treatment. Full article

To evaluate the expression profile of circulating miRNAs in patients with schizophrenia (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572, and miR-652) in relation to individual negative controls for the disease. This was an analytical, case-controlled, cross-sectional study, using samples previously collected from patients diagnosed with schizophrenia (N = 650) and a control group (N = 924). Samples were analyzed after RNA extraction and quantification. After making a general comparison between the case and control groups, regardless of gender and other variables, all seven miRNAs showed statistically significant differences (p-value < 0.05). This also occurred in the variables gender, smoking, and alcoholism. Thus, the results indicated that depending on the clinical characteristics in the face of suspected schizophrenia, the miRNAs explored here seem to work as possible biomarkers, as they demonstrated, at various times, important differences between the studied groups. Full article

Cognitive impairment in various mental illnesses, particularly neuropsychiatric disorders, has adverse functional and clinical consequences. While genetic mutations and epigenetic dysregulations of several genes during embryonic and adult periods are linked to cognitive impairment in mental disorders, the composition and diversity of resident bacteria in the gastrointestinal tract—shaped by environmental factors—also influence the brain epigenome, affecting behavior and cognitive functions. Accordingly, many recent studies have provided evidence that human gut microbiota may offer a potential avenue for improving cognitive deficits. In this review, we provide an overview of the relationship between cognitive impairment, alterations in the gut microbiome, and epigenetic alterations during embryonic and adult periods. We examine how various factors beyond genetics—such as lifestyle, age, and maternal diet—impact the composition, diversity, and epigenetic functionality of the gut microbiome, consequently influencing cognitive performance. Additionally, we explore the potential of maternal gut microbiome signatures and epigenetic biomarkers for predicting cognitive impairment risk in older adults. This article also explores the potential roles of nutritional deficiencies in programming cognitive disorders during the perinatal period in offspring, as well as the promise of gut microbiome-targeted therapeutics with epigenetic effects to prevent or alleviate cognitive dysfunctions in infants, middle-aged adults, and older adults. Unsolved challenges of gut microbiome-targeted therapeutics in mitigating cognitive dysfunctions for translation into clinical practice are discussed, lastly. Full article

Prostate cancer (PCa) is a major health burden worldwide, and despite early treatment, many patients present with biochemical recurrence (BCR) post-treatment, reflected by a rise in prostate-specific antigen (PSA) over a clinical threshold. Novel transcriptomic and epigenomic biomarkers can provide a powerful tools for the clinical management of PCa. Here, we provide matched RNA sequencing and array-based genome-wide DNA methylome data of PCa patients (n = 17) with or without evidence of BCR following radical prostatectomy. Formalin-fixed paraffin-embedded (FFPE) tissues were used to generate these data, which included technical replicates to provide further validity of the data. We describe the sample features, experimental design, methods and bioinformatic pipelines for processing these multi-omic data. Importantly, comprehensive clinical, histopathological, and follow-up data for each patient were provided to enable the correlation of transcriptome and methylome features with clinical features. Our data will contribute towards the efforts of developing epigenomic and transcriptomic markers for BCR and also facilitate a deeper understanding of the molecular basis of PCa recurrence. Full article

Background/Aim: Loss of smell, also known as anosmia, is a prevalent and often prolonged symptom following infection with SARS-CoV-2. While many patients regain olfactory function within weeks, a significant portion experience persistent anosmia lasting over a year post-infection. The underlying mechanisms responsible for this sensory deficit remain largely uncharacterized. Previous studies, including genome-wide association studies (GWAS), have identified genetic variants near the UGT2A1 and UGT2A2 genes that are linked to anosmia in COVID-19 patients. However, the role of epigenetic changes in the development and persistence of smell loss has not been well explored. In this study, we aimed to investigate epigenetic alterations in the form of DNA methylation in the UGT1A1 gene, which is a locus associated with olfactory dysfunction in COVID-19 patients. Methods: We analysed DNA methylation patterns in blood samples from two carefully matched cohorts of 20 COVID-19 patients each, which are differentiated by their olfactory function—those with normal smell (normosmia) and those suffering from smell loss (anosmia). The cohorts were matched for age and sex to minimize potential confounding factors. Results: Using quantitative analysis, we found significantly lower levels of DNA methylation in the UGT1A1 locus in the anosmia group compared to the normosmia group, with a 14% decrease in median methylation values in patients with smell loss (p < 0.0001). These findings highlight potential epigenomic alterations in the UGT1A1 gene that may contribute to the pathogenesis of anosmia following COVID-19 infection. Our results suggest that the methylation status at this locus could serve as a biomarker for olfactory dysfunction in affected individuals. Conclusion: This study is among the first to describe epigenetic changes associated with smell loss in COVID-19, providing a foundation for future research into targeted interventions and potential therapeutic strategies aimed at reversing persistent anosmia. Further investigations involving larger cohorts and additional loci may help elucidate the complex interaction between genetic, epigenetic, and environmental factors influencing long-term sensory impairment post-COVID-19. Full article

Background/Objectives: Aging is a natural physiological process involving biological and genetic pathways. Growing evidence suggests that alterations in the epigenome during aging result in transcriptional changes, which play a significant role in the onset of age-related diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. For this reason, the epigenetic alterations in aging and age-related diseases have been reviewed, and the major extrinsic factors influencing these epigenetic alterations have been identified. In addition, the role of the gut microbiome and its metabolites as epigenetic modifiers has been addressed. Results: Long-term exposure to extrinsic factors such as air pollution, diet, drug use, environmental chemicals, microbial infections, physical activity, radiation, and stress provoke epigenetic changes in the host through several endocrine and immune pathways, potentially accelerating the aging process. Diverse studies have reported that the gut microbiome plays a critical role in regulating brain cell functions through DNA methylation and histone modifications. The interaction between genes and the gut microbiome serves as a source of adaptive variation, contributing to phenotypic plasticity. However, the molecular mechanisms and signaling pathways driving this process are still not fully understood. Conclusions: Extrinsic factors are potential inducers of epigenetic alterations, which may have important implications for longevity. The gut microbiome serves as an epigenetic effector influencing host gene expression through histone and DNA modifications, while bidirectional interactions with the host and the underexplored roles of microbial metabolites and non-bacterial microorganisms such as fungi and viruses highlight the need for further research. Full article