scholarly journals Longevity Factor FOXO3: A Key Regulator in Aging-Related Vascular Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan Zhao ◽  
You-Shuo Liu
Keyword(s):  
Environmental Changes ◽  
Critical Role ◽  
Experimental Studies ◽  
Metabolic Stress ◽  
Vascular Diseases ◽  
Human Longevity ◽  
Nucleotide Polymorphisms ◽  
Vascular Aging ◽  
Single Nucleotide ◽  
Forkhead Box

Forkhead box O3 (FOXO3) has been proposed as a homeostasis regulator, capable of integrating multiple upstream signaling pathways that are sensitive to environmental changes and counteracting their adverse effects due to external changes, such as oxidative stress, metabolic stress and growth factor deprivation. FOXO3 polymorphisms are associated with extreme human longevity. Intriguingly, longevity-associated single nucleotide polymorphisms (SNPs) in human FOXO3 correlate with lower-than-average morbidity from cardiovascular diseases in long-lived people. Emerging evidence indicates that FOXO3 plays a critical role in vascular aging. FOXO3 inactivation is implicated in several aging-related vascular diseases. In experimental studies, FOXO3-engineered human ESC-derived vascular cells improve vascular homeostasis and delay vascular aging. The purpose of this review is to explore how FOXO3 regulates vascular aging and its crucial role in aging-related vascular diseases.

scholarly journals HSD17B13: A Potential Therapeutic Target for NAFLD

2022 ◽  
Vol 8 ◽  
Author(s):  
Hai-bo Zhang ◽  
Wen Su ◽  
Hu Xu ◽  
Xiao-yan Zhang ◽  
You-fei Guan
Keyword(s):  
Liver Disease ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Critical Role ◽  
Chronic Liver ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Nonalcoholic Fatty Liver ◽  
Promising Target ◽  
Associated Proteins

Nonalcoholic fatty liver disease (NAFLD), especially in its inflammatory form (steatohepatitis, NASH), is closely related to the pathogenesis of chronic liver disease. Despite substantial advances in the management of NAFLD/NASH in recent years, there are currently no efficacious therapies for its treatment. The biogenesis and expansion of lipid droplets (LDs) are critical pathophysiological processes in the development of NAFLD/NASH. In the past decade, increasing evidence has demonstrated that lipid droplet-associated proteins may represent potential therapeutic targets for the treatment of NAFLD/NASH given the critical role they play in regulating the biogenesis and metabolism of lipid droplets. Recently, HSD17B13, a newly identified liver-enriched, hepatocyte-specific, lipid droplet-associated protein, has been reported to be strongly associated with the development and progression of NAFLD/NASH in both mice and humans. Notably, human genetic studies have repeatedly reported a robust association of HSD17B13 single nucleotide polymorphisms (SNPs) with the occurrence and severity of NAFLD/NASH and other chronic liver diseases (CLDs). Here we briefly overview the discovery, tissue distribution, and subcellular localization of HSD17B13 and highlight its important role in promoting the pathogenesis of NAFLD/NASH in both experimental animal models and patients. We also discuss the potential of HSD17B13 as a promising target for the development of novel therapeutic agents for NAFLD/NASH.

scholarly journals Modulation of human longevity by SIRT3 single nucleotide polymorphisms in the prospective study “Treviso Longeva (TRELONG)”

AGE ◽  
2013 ◽  
Vol 36 (1) ◽  
pp. 469-478 ◽  
Author(s):  
Diego Albani ◽  
Eleonora Ateri ◽  
Stefano Mazzuco ◽  
Alice Ghilardi ◽  
Serena Rodilossi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Prospective Study ◽  
Human Longevity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals The Genetic and Environmental Adaptation of the Associated Liana Species Derris trifoliata Lour. (Leguminosae) in Mangroves

Forests ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1375
Author(s):  
Yun Zhang ◽  
Kun Xin ◽  
Baowen Liao ◽  
Xihang Ai ◽  
Nong Sheng
Keyword(s):  
Clonal Growth ◽  
Environmental Changes ◽  
Principal Component ◽  
Clonal Diversity ◽  
Control Measures ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Sexual Propagation ◽  
Specific Locus ◽  
And Control

Derris trifoliata Lour. is an indigenous and associated liana species of mangroves in China; however, its rapid dispersal is threatening mangrove survival. To explore and evaluate their persistence in past disturbances and their potential resistance to future climate and environmental changes, 120 D. trifoliata samples were collected from three sites in Guangdong Province, China, and they were used to develop single nucleotide polymorphic markers using specific-locus amplified fragment sequencing technology. A total of 351.59 Mb reads and 97,998 polymorphic specific-locus amplified fragment sequencing tags were identified, including 360,672 single nucleotide polymorphisms. The principal component analysis, phylogenetic tree, and genetic structure all clustered the samples according to their geographic positions. The three populations showed medium genetic diversity levels and high clonal diversity, indicating that sexual propagation played vital roles in the populations’ succession, although clonal growth was intense within the populations. An association analysis revealed that 9 out of 16 markers were correlated with nitrogen, which indicated the positive roles of nitrogen in population formation and maintenance. This study provides an ecological and molecular basis for understanding the outbreaks of D. trifoliata in mangroves. To control the further expansion of D. trifoliata in mangroves, preventive and control measures should be taken against clonal growth and sexual propagation, respectively; obstructing the clonal growth, especially that of the stolon, should be mainly considered at the junctions of D. trifoliata and mangroves.

scholarly journals Chromosome-Wide Characterization of Intragenic Crossover in Shiitake Mushroom, Lentinula edodes

2021 ◽  
Vol 7 (12) ◽  
pp. 1076
Author(s):  
Wenbing Gong ◽  
Nan Shen ◽  
Lin Zhang ◽  
Yinbing Bian ◽  
Yang Xiao
Keyword(s):  
Lentinula Edodes ◽  
Critical Role ◽  
Central Component ◽  
Nucleotide Polymorphisms ◽  
Single Spore ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Cis And Trans ◽  
Qtls Mapping

Meiotic crossover plays a critical role in generating genetic variations and is a central component of breeding. However, our understanding of crossover in mushroom-forming fungi is limited. Here, in Lentinula edodes, we characterized the chromosome-wide intragenic crossovers, by utilizing the single-nucleotide polymorphisms (SNPs) datasets of an F1 haploid progeny. A total of 884 intragenic crossovers were identified in 110 single-spore isolates, the majority of which were closer to transcript start sites. About 71.5% of the intragenic crossovers were clustered into 65 crossover hotspots. A 10 bp motif (GCTCTCGAAA) was significantly enriched in the hotspot regions. Crossover frequencies around mating-type A (MAT-A) loci were enhanced and formed a hotspot in L. edodes. Genome-wide quantitative trait loci (QTLs) mapping identified sixteen crossover-QTLs, contributing 8.5–29.1% of variations. Most of the detected crossover-QTLs were co-located with crossover hotspots. Both cis- and trans-QTLs contributed to the nonuniformity of crossover along chromosomes. On chr2, we identified a QTL hotspot that regulated local, global crossover variation and crossover hotspot in L. edodes. These findings and observations provide a comprehensive view of the crossover landscape in L. edodes, and advance our understandings of conservation and diversity of meiotic recombination in mushroom-forming fungi.

scholarly journals A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene

Cholesterol ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Francisco R. Marín-Martín ◽  
Cristina Soler-Rivas ◽  
Roberto Martín-Hernández ◽  
Arantxa Rodriguez-Casado
Keyword(s):  
In Silico ◽  
Rare Variants ◽  
Experimental Studies ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Experimental Approaches ◽  
And Function

Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from in vitro, in vivo, and human studies. Out of a total of 233 nsSNPs, 80 (34.33%) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44%) rare variants resulted highly deleterious with a probability >0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them. A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2.

scholarly journals Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt

2017 ◽  
Vol 11 (03) ◽  
pp. 261-268 ◽  
Author(s):  
Hany Khalil ◽  
Mohamed Arfa ◽  
Samir El-Masrey ◽  
Sherif M EL-Sherbini ◽  
Amal A Abd-Elaziz
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Single Nucleotide Polymorphisms ◽  
Critical Role ◽  
Interleukin 10 ◽  
High Rate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mutant Genotype

Introduction: Hepatitis C is a liver disease caused by the hepatitis C virus (HCV). It can cause both acute and chronic hepatitis infection. Based on secretion of required cytokines upon infection, HCV can improve its own RNA and successfully complete the replication cycle. Importantly, single nucleotide polymorphisms (SNPs) are the most common type of genetic variation and have been found to play a critical role in modulation of cellular cytokine production and interaction. Methodology: A total of 100 blood samples were obtained from HCV patients, and 120 samples were obtained from healthy individuals who served as controls. SNPs of interleukin-10/592 (IL-10/592) and IL-4/589 were investigated for possible connection with HCV infection. Relative expression of IL-4, IL-6, and IL-10 were detected using real-time polymerase chain reaction and enzyme-linked immunosorbent assay Results: The polymorphisms of IL-10 revealed a high rate of mutant genotype CC within the location IL-10/592 in HCV patients and controls, which resulted in low secretion of IL-10. Interestingly, the findings here demonstrate a positive association between HCV load of viremia and the mutant genotype IL-4-589/TT accompanied with low expression IL-4 in comparison with IL-6 expression. Conclusions: These data suggest that the expression of IL-4 is inversely proportional to HCV load of viremia, and this connection is due to the high level of mutant genotype IL-4-589/TT in infected patients located in gene promoter and inhibits gene expression.  

scholarly journals Impact of Gene–Environment Interactions on Cancer Development

2020 ◽  
Vol 17 (21) ◽  
pp. 8089
Author(s):  
Ariane Mbemi ◽  
Sunali Khanna ◽  
Sylvianne Njiki ◽  
Clement G. Yedjou ◽  
Paul B. Tchounwou
Keyword(s):  
Environmental Factors ◽  
Scientific Evidence ◽  
Critical Role ◽  
Experimental Studies ◽  
Joint Effect ◽  
Human Diseases ◽  
Nucleotide Polymorphisms ◽  
Gene Environment ◽  
Genetic And Environmental Factors ◽  
The Impact

Several epidemiological and experimental studies have demonstrated that many human diseases are not only caused by specific genetic and environmental factors but also by gene–environment interactions. Although it has been widely reported that genetic polymorphisms play a critical role in human susceptibility to cancer and other chronic disease conditions, many single nucleotide polymorphisms (SNPs) are caused by somatic mutations resulting from human exposure to environmental stressors. Scientific evidence suggests that the etiology of many chronic illnesses is caused by the joint effect between genetics and the environment. Research has also pointed out that the interactions of environmental factors with specific allelic variants highly modulate the susceptibility to diseases. Hence, many scientific discoveries on gene–environment interactions have elucidated the impact of their combined effect on the incidence and/or prevalence rate of human diseases. In this review, we provide an overview of the nature of gene–environment interactions, and discuss their role in human cancers, with special emphases on lung, colorectal, bladder, breast, ovarian, and prostate cancers.

scholarly journals rs2253310 and rs4946936 common variants of FOXO3 gene in octogenarians and cancer: a pilot study in north India

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Neelam Tia ◽  
Moti Lal ◽  
I. S. Gambhir
Keyword(s):  
Pilot Study ◽  
Indian Population ◽  
Study Groups ◽  
Human Longevity ◽  
Main Body ◽  
North Indian Population ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
The North ◽  
Forkhead Box

Abstract Background Healthy aging perceives human longevity probably due to carrying the defensive genes. Forkhead box O (FOXO) transcription factors provide the most convincing example of a conserved genetic pathway at the point between aging and cancer. This pilot study was performed to examine the single nucleotide variants rs2253310 and rs4946936 of the Forkhead box O 3 (FOXO3 gene) in octogenarians and gastrointestinal tract (GIT) cancer patients in the north Indian population. Main body In silico mutational analysis of the FOXO3 gene in 25 participants. Two single nucleotide variants (SNVs) g.7556C>G (rs2253310) heterozygous and g.122284T>C (rs4946936) homozygous observed and reported previously. However, there is a common association of these SNVs in different ethnic groups. No significant differences in the genotype and allele frequencies for the study groups observed. Short conclusion This study observes two single nucleotide variants, g.7556C>G (rs2253310) and g.122284T>C (rs4946936), of the FOXO3 gene in the study groups which influence human longevity. Longevity-associated FOXO3 variants may be associated with GIT cancer in the north Indian population. As a result, looking for genes linked to longevity will lead to discovering new cancer targets. Further studies with a large population are necessary to elucidate the role of the FOXO3 gene in octogenarians.

scholarly journals The effect of Alzheimer’s disease-associated genetic variants on longevity

2021 ◽  
Author(s):  
Niccolò Tesi ◽  
Marc Hulsman ◽  
Sven J. van der Lee ◽  
Iris E. Jansen ◽  
Najada Stringa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Longevity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Immune Signaling ◽  
Age Related ◽  
Increased Risk ◽  
Parental Longevity ◽  
Effect Size Distribution

AbstractThe genetics underlying human longevity is influenced by the genetic risk to develop -or escape- age-related diseases. As Alzheimer’s disease (AD) represents one of the most common conditions at old age, an interplay between genetic factors for AD and longevity is expected.We explored this interplay by studying the prevalence of 38 AD-associated single-nucleotide-polymorphisms (SNPs) identified in AD-GWAS, in self-reported cognitively healthy centenarians, and we replicated findings in the largest GWAS on parental-longevity.We found that 28/38 SNPs identified to associate with increased AD-risk also associated with decreased odds of longevity. For each SNP, we express the imbalance between AD- and longevity-risk as an effect-size distribution. When grouping the SNPs based on these distributions, we found three groups: 17 variants increased AD-risk more than they decreased the risk of longevity (AD-group): these variants were functionally enriched for β-amyloid metabolism and immune signaling, and they were enriched in microglia. 11 variants reported a larger effect on longevity as compared to their AD-effect (Longevity-group): these variants were enriched for endocytosis/immune signaling, and at the cell-type level were enriched in microglia and endothelial cells. Next to AD, these variants were previously associated with other aging-related diseases, including cardiovascular and autoimmune diseases, and cancer. Unexpectedly, 10 variants associated with an increased risk of both AD and longevity (Unexpected-group). The effect of the SNPs in AD- and Longevity-groups replicated in the largest GWAS on parental-longevity, while the effects on longevity of the SNPs in the Unexpected-group could not be replicated, suggesting that these effects may not be robust across different studies.Our study shows that some AD-associated variants negatively affect longevity primarily by their increased risk of AD, while other variants negatively affect longevity through an increased risk of multiple age-related diseases, including AD.

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