scholarly journals INTERACTIONS BETWEEN GENES FROM AGING-RELATED PATHWAYS: IMPACT ON HUMAN LONGEVITY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S899-S899
Author(s):  
Svetlana Ukraintseva ◽  
Matt Duan ◽  
Deqing Wu ◽  
Konstantin Arbeev ◽  
Alexander Kulminski ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Genetic Heterogeneity ◽  
Significant Interaction ◽  
Oldest Old ◽  
Interaction Effects ◽  
Genetic Interactions ◽  
Human Longevity ◽  
Cell Responses ◽  
Nominal Significance

Abstract Role of genetic interactions (GxG) in human longevity remains poorly understood. We hypothesized that GxG between genes from biologically connected pathways involved in aging may impact longevity. To test this hypothesis, we selected 53 candidate genes from the aging-related pathways (IGF-1/AKT/FOXO3A, TP53/P21/P16, and mTOR/S6K mediated) that are known to jointly influence outcomes of cell responses to stress and damage, such as apoptosis, senescence, growth/proliferation, and autophagy. We evaluated the effects of interactions between SNPs in these genes on longevity in LLFS and CARe data. RESULTS: The IGF1R, PPARGC1A and BCL2 genes were consistently involved in top GxG effects (p<10-6) on survival in the oldest old (85+ and 95+). One SNP, rs2970870 in PPARGC1A gene, was broadly involved in significant interaction effects on survival 96+ (p<10-7) when paired with SNPs in IGF1R and NFKB1 genes. This SNP individually was associated with survival with nominal significance only; therefore, it would have not been selected in a GWAS. We conclude that interactions between genes from aging-related pathways that regulate cell responses and resilience to damage may have major impact on human longevity and contribute to its genetic heterogeneity. The research was supported by the NIA/NIH grants R01AG062623, U19AG063893, P01AG043352.

WHEN A SMILE DOES NO GOOD: CREATIVITY REDUCTION AMONG AVOIDANCE- VERSUS APPROACH-ORIENTED INDIVIDUALS IN DYADIC INTERACTIONS

2016 ◽  
Vol 20 (04) ◽  
pp. 1640007 ◽  
Author(s):  
KEN FUJIWARA ◽  
KOSUKE TAKEMURA ◽  
SATOKO SUZUKI
Keyword(s):  
Significant Interaction ◽  
Interaction Effects ◽  
Social Approval ◽  
Dyadic Interactions ◽  
Same Sex ◽  
Popular Belief ◽  
Drawing Task

This study examined the influence of others’ smiles on individuals’ creativity. According to popular belief, individuals get motivated to be more creative when others smile at them. In contrast, we hypothesised that smiles would make avoidance-oriented (versus approach-oriented) individuals less creative, as they may lose the motivation to pursue further novelty once they gain social approval, as implied by a smile. Forty-two participants were paired with a same-sex stranger and randomly assigned to the role of either an “illustrator” or a “commentator.” The illustrators performed the Alien Drawing Task and the commentators gave feedbacks regarding the drawing, which were repeated six times and video-recorded. As expected, the results showed significant interaction effects between others’ smiles and avoidance orientation on creativity: participants high in avoidance orientation showed less creativity when others smiled at them. In addition, nodding had the same effect as a smile did, confirming that social approval decreases the creativity of avoidance-oriented individuals.

scholarly journals Role of Genetic Interactions in Alzheimer’s Disease: Lessons from Long Life Family Study (LLFS)

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 491-491
Author(s):  
Anatoliy Yashin ◽  
Dequing Wu ◽  
Konstantin Arbeev ◽  
Eric Stallard ◽  
Qihua Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family Study ◽  
Interaction Analysis ◽  
Specific Interaction ◽  
Interaction Effects ◽  
Genetic Interactions ◽  
Risk Scores ◽  
Long Life

Abstract Experimental and clinical studies of Alzheimer’s disease (AD) provide plentiful evidence of AD heterogeneity and involvement of many interacting genes and pathways in regulation of AD-related traits. However, detailed mechanisms of genetic interactions (GxG) involved in AD remain largely unknown. Uncovering hidden patterns of such interactions from human data will help better understand the nature of AD heterogeneity and find new targets for AD prevention. In this paper, we applied a newly developed method of evaluating joint GxG effects on AD to analysis of the Long Life Family Study data. The analysis included several steps: (i) selecting candidate genes from stress response pathways that are thought to be involved in AD; (ii) estimating interaction effects of SNP-pairs on AD risk, and selecting the top interacting SNPs; (iii) running GWAS-like interaction analysis for SNP-pairs, with one SNP fixed; (iv) using characteristics of the detected SNP-pairs interactions to construct the SNP-specific Interaction Polygenic Risk Scores (IPRS); and (v) evaluating the effects of IPRSs on AD. We found that SNP-specific IPRS have highly significant effects on AD risk. For most SNPs involved in the significant interaction effects on AD, their individual effects were statistically not significant. Male and female analyses yielded different subsets of the top interacting SNPs. These results support major role of genetic interactions in heterogeneity of AD, and indicate that AD mechanisms can involve different combinations of the interacting genetic variants in males and females, which may point to different pathways of resistance/response to stressors in two genders.

scholarly journals Stress Mediating Genes in Aging, Health, and Longevity Traits: Effects of Multiple Interactions

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 286-286
Author(s):  
Anatoliy Yashin ◽  
Dequing Wu ◽  
Konstantin Arbeev ◽  
Arseniy Yashkin ◽  
Galina Gorbunova ◽  
...  
Keyword(s):  
Strong Interaction ◽  
Genetic Interaction ◽  
Interaction Effects ◽  
Genetic Interactions ◽  
Risk Scores ◽  
Data Sets ◽  
Interaction Patterns ◽  
Polygenic Risk ◽  
Drug Candidates ◽  
Aging Health

Abstract Persistent stress of external or internal origin accelerates aging, increases risk of aging related health disorders, and shortens lifespan. Stressors activate stress response genes, and their products collectively influence traits. The variability of stressors and responses to them contribute to trait heterogeneity, which may cause the failure of clinical trials for drug candidates. The objectives of this paper are: to address the heterogeneity issue; to evaluate collective interaction effects of genetic factors on Alzheimer’s disease (AD) and longevity using HRS data; to identify differences and similarities in patterns of genetic interactions within two genders; and to compare AD related genetic interaction patterns in HRS and LOADFS data. To reach these objectives we: selected candidate genes from stress related pathways affecting AD/longevity; implemented logistic regression model with interaction term to evaluate effects of SNP-pairs on these traits for males and females; constructed the novel interaction polygenic risk scores for SNPs, which showed strong interaction potential, and evaluated effects of these scores on AD/longevity; and compared patterns of genetic interactions within the two genders and within two datasets. We found there were many genes involved in highly significant interactions that were the same and that were different within the two genders. The effects of interaction polygenic risk scores on AD were strong and highly statistically significant. These conclusions were confirmed in analyses of interaction effects on longevity trait using HRS data. Comparison of HRS to LOADFS data showed that many genes had strong interaction effects on AD in both data sets.

scholarly journals The SARS-CoV-2/Receptor Axis in Heart and Blood Vessels: A Crisp Update on COVID-19 Disease with Cardiovascular Complications

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1346
Author(s):  
Priya Veluswamy ◽  
Max Wacker ◽  
Dimitrios Stavridis ◽  
Thomas Reichel ◽  
Hendrik Schmidt ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Cardiovascular Complications ◽  
World Health ◽  
Endothelial Glycocalyx ◽  
Pathological State ◽  
Mediated Action ◽  
Cell Responses ◽  
Health Organization

The SARS-CoV-2 virus causing COVID-19 disease has emerged expeditiously in the world and has been declared pandemic since March 2020, by World Health Organization (WHO). The destructive effects of SARS-CoV-2 infection are increased among the patients with pre-existing chronic conditions and, in particular, this review focuses on patients with underlying cardiovascular complications. The expression pattern and potential functions of SARS-CoV-2 binding receptors and the attributes of SARS-CoV-2 virus tropism in a physio-pathological state of heart and blood vessel are precisely described. Of note, the atheroprotective role of ACE2 receptors is reviewed. A detailed description of the possible detrimental role of SARS-CoV-2 infection in terms of vascular leakage, including endothelial glycocalyx dysfunction and bradykinin 1 receptor stimulation is concisely stated. Furthermore, the potential molecular mechanisms underlying SARS-CoV-2 induced clot formation in association with host defense components, including activation of FXIIa, complements and platelets, endothelial dysfunction, immune cell responses with cytokine-mediated action are well elaborated. Moreover, a brief clinical update on patient with COVID-19 disease with underlying cardiovascular complications and those who had new onset of cardiovascular complications post-COVID-19 disease was also discussed. Taken together, this review provides an overview of the mechanistic aspects of SARS-CoV-2 induced devastating effects, in vital organs such as the heart and vessels.

scholarly journals T cell–specific STAT3 deficiency abrogates lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1468-1472 ◽  
Author(s):  
N Yoshida ◽  
F He ◽  
V C Kyttaris
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Cell Responses ◽  
Cytokines And Chemokines ◽  
Novel Approach ◽  
Cell Tissue ◽  
External Stimuli

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.

scholarly journals Internal and External Resources of the Lifestyle Leaders

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 612-612
Author(s):  
Martina Raue ◽  
Lisa D’Ambrosio ◽  
Taylor Patskanick ◽  
John Rudnik ◽  
Adam Felts ◽  
...  
Keyword(s):  
Physical Health ◽  
Significant Role ◽  
Oldest Old ◽  
Well Being ◽  
Self Esteem ◽  
Financial Resources ◽  
External Resources ◽  
Resource Decline ◽  
New Challenges

Abstract With older age, people experience declines in resources and face new challenges. The goal of this study was to understand how resource decline affects the oldest olds’ well-being, but also to learn who they trust and where they go for advice in areas such as health, finances, and technology. This sample of 30 participants between the ages of 85 and 95 was generally resource-rich, scoring highest on self-esteem and optimism and lowest on mastery. Self-esteem and optimism correlated with financial resources, indicating a significant role of finances in this rather wealthy sample. Well-being was predicted by self-esteem and physical health. Presumably, their high levels of self-esteem compensate for the loss of other resources among the oldest old. The majority of lifestyle leaders trust in other people, and while friends and family are very important sources of advice, searching online was equally often mentioned as a source when looking for advice.

scholarly journals Role of dendritic cell metabolic reprogramming in tumor immune evasion

2020 ◽  
Vol 32 (7) ◽  
pp. 485-491 ◽  
Author(s):  
Michael P Plebanek ◽  
Michael Sturdivant ◽  
Nicholas C DeVito ◽  
Brent A Hanks
Keyword(s):  
Dendritic Cell ◽  
Metabolic Pathways ◽  
Checkpoint Inhibitor ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Combination Immunotherapy ◽  
Tumor Immune Evasion ◽  
Effector T Cell ◽  
Cell Responses

Abstract The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of DCs dictates their functionality and can determine which DCs become immunostimulatory versus those that develop a tolerized phenotype capable of actively suppressing effector T-cell responses to cancers. As a result, there is great interest in understanding what mechanisms have evolved in cancers to alter these metabolic pathways, thereby allowing for their continued progression and metastasis. The therapeutic strategies developed to reverse these processes of DC tolerization in the tumor microenvironment represent promising candidates for future testing in combination immunotherapy clinical trials.

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