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The current increase in lifespan without an equivalent increase in healthspan poses a grave challenge to the healthcare system and a severe burden on society. However, some individuals seem to be able to live a long and healthy life without the occurrence of major debilitating chronic diseases, and part of this trait seems to be hidden in their genome. In this review, we discuss the findings from studies on the genetic component of human longevity and the main challenges accompanying these studies. We subsequently focus on results from genetic studies in model organisms and comparative genomic approaches to highlight the most important conserved longevity-associated pathways. By combining the results from studies using these different approaches, we conclude that only five main pathways have been consistently linked to longevity, namely (1) insulin/insulin-like growth factor 1 signalling, (2) DNA-damage response and repair, (3) immune function, (4) cholesterol metabolism and (5) telomere maintenance. As our current approaches to study the relevance of these pathways in humans are limited, we suggest that future studies on the genetics of human longevity should focus on the identification and functional characterization of rare genetic variants in genes involved in these pathways., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Dietary intervention is a subject of growing interest in the management of inflammatory bowel disease (IBD), as new incident cases across the globe are rapidly rising, suggesting environmental factors as contributing elements. Dietary components and micronutrients have been associated with IBD pathogenesis or reductions in disease severity. Selenium, a diet-derived essential micronutrient that is important for proper immune system function, has received limited attention in the context of IBD. Selenium deficiency is a common finding in patients with IBD, but few clinical trials have been published to address the consequences of this deficiency. Here, we review the physiological and immunological roles of selenium and its putative role in IBD, and draw attention to knowledge gaps and unresolved issues, with the goal of stimulating more research on selenium in IBD. [ABSTRACT FROM AUTHOR]

Background: The minor G-allele of FOXO3 rs2802292 is associated with human longevity. The aim of this study was to test the protective effect of the variant against the association with type 2 Diabetes and NAFLD. Methods: rs2802292 was genotyped in a large population of middle-aged subjects (n = 650) from a small city in Southern Italy. All participants were interviewed to collect information about lifestyle and dietary habits; clinical characteristics were recorded, and blood samples were collected from all subjects. The association between rs2802292 and NAFLD or diabetes was tested using a logistic model and mediation analysis adjusted for covariates. Results: Overall, the results indicated a statistical association between diabetes and rs2802292, especially for the TT genotype (OR = 2.14, 1.01 to 4.53 95% C.I., p = 0.05) or in any case for those who possess the G-allele (OR = 0.45, 0.25 to 0.81 95% C.I., p = 0.008). Furthermore, we found a mediation effect of rs2802292 on diabetes (as mediator) and NAFLD. There is no direct relationship between rs2802292 and NAFLD, but the effect is direct (β = 0.10, −0.003 to 0.12 95% C.I., p = 0.04) on diabetes, but only in TT genotypes. Conclusions: The data on our cohort indicate that the longevity-associated FOXO3 variant may have protective effects against diabetes and NAFLD. [ABSTRACT FROM AUTHOR]

There have been many studies reporting that the regular consumption of fruits and vegetables is associated with reduced risks of cancer and age-related chronic diseases. Recent studies have demonstrated that reducing reactive oxygen species and inflammation by phytochemicals derived from natural sources can extend lifespans in a range of model organisms. Phytochemicals derived from fruits and vegetables have been known to display both preventative and suppressive activities against various types of cancer via in vitro and in vivo research by interfering with cellular processes critical for tumor development. The current challenge lies in creating tailored supplements containing specific phytochemicals for individual needs. Achieving this goal requires a deeper understanding of the molecular mechanisms through which phytochemicals affect human health. In this review, we examine recently (from 2010 to 2024) reported plant extracts and phytochemicals with established anti-aging and anti-cancer effects via the activation of FOXO3 transcriptional factor. Additionally, we provide an overview of the cellular and molecular mechanisms by which these molecules exert their anti-aging and anti-cancer effects in specific model systems. Lastly, we discuss the limitations of the current research approach and outline for potential future directions in this field. [ABSTRACT FROM AUTHOR]

Background: Aging is a prominent risk factor for diverse diseases; therefore, an in-depth understanding of its physiological mechanisms is required. Nonhuman primates, which share the closest genetic relationship with humans, serve as an ideal model for exploring the complex aging process. However, the potential of the nonhuman primate animal model in the screening of human aging markers is still not fully exploited. Multiomics analysis of nonhuman primate peripheral blood offers a promising approach to evaluate new therapies and biomarkers. This study explores aging-related biomarker through multilayer omics, including transcriptomics (mRNA, lncRNA, and circRNA) and proteomics (serum and serum-derived exosomes) in rhesus monkeys (Macaca mulatta). Results: Our findings reveal that, unlike mRNAs and circRNAs, highly expressed lncRNAs are abundant during the key aging period and are associated with cancer pathways. Comparative analysis highlighted exosomal proteins contain more types of proteins than serum proteins, indicating that serum-derived exosomes primarily regulate aging through metabolic pathways. Finally, eight candidate aging biomarkers were identified, which may serve as blood-based indicators for detecting age-related brain changes. Conclusions: Our results provide a comprehensive understanding of nonhuman primate blood transcriptomes and proteomes, offering novel insights into the aging mechanisms for preventing or treating age-related diseases. [ABSTRACT FROM AUTHOR]

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1–10 µg/mL (0.01—1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec's modulation of the immune response compared to control groups. rBanLec administration resulted in an inverse dose–response reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in homologous regions play a critical role in the field of genetics. However, genotyping these SNPs is challenging due to the presence of repetitive sequences within genome, which demand specific method. We introduce a new, mid-throughput method that simplifies SNP genotyping in homologous DNA sequences by utilizing a combination of multiplex kb level PCR (PCR size 2.5k-3.5 kb) for capturing targeted regions and multiplex nested PCR library construction for next-generation sequencing (Multi-kb level capture-seq). First of all, we randomly selected 7 SNPs in homologous regions and successfully captured 6-plex kb level amplicons (one of segments contains 2 SNPs, while the remaining segments each have only one SNP) in a single tube. And then, the amplification products were subjected to multiplex nested PCR for library construction and sequenced on Illumina platform. We tested this strategy using 600 amplicons from 100 samples and accurately genotyped 96.8% of target SNPs with a coverage depth of ≥ 15×. For the uniformity within the samples, over 66.7% (4/6) of the amplicons had a coverage depth above 0.2-fold of average sequencing depth. To validate the accuracy of this approach, we performed Ligase detection reaction PCR for genotyping the 100 samples, and found that the genotyping data was 97.71% consistent with our NGS results. In conclusion, we have developed a highly efficient and accurate method for SNP genotyping in homologous regions, which offers researchers a new strategy to explore the complex regions of genome., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inflammatory bowel disease (IBD) belongs to a group of autoimmune conditions characterized by chronic inflammation and mucosal ulceration of the gastrointestinal tract. The etiology of IBD is complex. The etiological factors include environmental factors, among which diet is important. The aim of this study was to evaluate the diet of IBD patients. This case–control study was carried out on 82 patients with IBD; the control group consisted of 80 clinically healthy subjects. Food intake was assessed using a 24 h recall and frequency food questionnaire. Energy intake in the IBD group was insufficient and significantly lower than in the control group. The energy intake in the group of patients with active IBD was significantly lower than in the group of subjects in remission. The total fat and protein intake was significantly lower in the IBD group compared to the healthy subjects. IBD patients were characterized by underconsumption of all food groups analyzed, except for the intake of red meat and poultry. Our study showed inadequate intake of energy and most nutrients in IBD patients, even during the remission period. The study indicates the need for routine assessment of dietary intake and nutrition among IBD patients, as well as potential dietary interventions aimed at improving the energy and nutritional quality of diet in order to optimize treatment outcomes and prevent the development of accompanying diseases. [ABSTRACT FROM AUTHOR]

Backgrounding: Stayability, which may be defined as the probability of a cow remaining in the herd until a reference age or at a specific number of calvings, is usually measured late in the animal's life. Thus, if used as selection criteria, it will increase the generation interval and consequently might decrease the annual genetic gain. Measuring stayability at an earlier age could be a reasonable strategy to avoid this problem. In this sense, a better understanding of the genetic architecture of this trait at different ages and/or at different calvings is important. This study was conducted to identify possible regions with major effects on stayability measured considering different numbers of calvings in Nellore cattle as well as pathways that can be involved in its expression throughout the female's productive life. Results: The top 10 most important SNP windows explained, on average, 17.60% of the genetic additive variance for stayability, varying between 13.70% (at the eighth calving) and 21% (at the fifth calving). These SNP windows were located on 17 chromosomes (1, 2, 4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, 19, 20, 27, and 28), and they harbored a total of 176 annotated genes. The functional analyses of these genes, in general, indicate that the expression of stayability from the second to the sixth calving is mainly affected by genetic factors related to reproductive performance, and nervous and immune systems. At the seventh and eighth calvings, genes and pathways related to animal health, such as density bone and cancer, might be more relevant. Conclusion: Our results indicate that part of the target genomic regions in selecting for stayability at earlier ages (from the 2th to the 6th calving) would be different than selecting for this trait at later ages (7th and 8th calvings). While the expression of stayability at earlier ages appeared to be more influenced by genetic factors linked to reproductive performance together with an overall health/immunity, at later ages genetic factors related to an overall animal health gain relevance. These results support that selecting for stayability at earlier ages (perhaps at the second calving) could be applied, having practical implications in breeding programs since it could drastically reduce the generation interval, accelerating the genetic progress. [ABSTRACT FROM AUTHOR]

In Germany and worldwide, the average age of the population is continuously rising. With this general increase in chronological age, the focus on biological age, meaning the actual health and fitness status, is becoming more and more important. The key question is to what extent the age-related decline in fitness is genetically predetermined or malleable by environmental factors and lifestyle.Many epigenetic studies in aging research have provided interesting insights in this nature-versus-nurture debate. In most model organisms, aging is associated with specific epigenetic changes, which can be countered by certain interventions like moderate caloric restriction or increased physical activity. Since these interventions also have positive effects on lifespan and health, epigenetics appears to be the interface between environmental factors and the aging process. This notion is supported by the fact that an epigenetic drift occurs through the life course of identical twins, which is related to the different manifestations of aging symptoms. Furthermore, biological age can be determined with high precision based on DNA methylation patterns, further emphasizing the importance of epigenetics in aging.This article provides an overview of the importance of genetic and epigenetic parameters for life expectancy. A major focus will be on the possibilities of maintaining a young epigenome through lifestyle and environmental factors, thereby slowing down biological aging., (© 2024. The Author(s).)