scholarly journals Genomic Approach to Understand the Association of DNA Repair with Longevity and Healthy Aging Using Genomic Databases of Oldest-Old Population

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yeo Jin Kim ◽  
Hyun Soo Kim ◽  
Young Rok Seo
Keyword(s):  
Dna Repair ◽  
Biological Networks ◽  
Genetic Variants ◽  
Healthy Aging ◽  
Oldest Old ◽  
Genomic Research ◽  
Human Longevity ◽  
Genomic Databases ◽  
Aged Population ◽  
Genomic Study

Aged population is increasing worldwide due to the aging process that is inevitable. Accordingly, longevity and healthy aging have been spotlighted to promote social contribution of aged population. Many studies in the past few decades have reported the process of aging and longevity, emphasizing the importance of maintaining genomic stability in exceptionally long-lived population. Underlying reason of longevity remains unclear due to its complexity involving multiple factors. With advances in sequencing technology and human genome-associated approaches, studies based on population-based genomic studies are increasing. In this review, we summarize recent longevity and healthy aging studies of human population focusing on DNA repair as a major factor in maintaining genome integrity. To keep pace with recent growth in genomic research, aging- and longevity-associated genomic databases are also briefly introduced. To suggest novel approaches to investigate longevity-associated genetic variants related to DNA repair using genomic databases, gene set analysis was conducted, focusing on DNA repair- and longevity-associated genes. Their biological networks were additionally analyzed to grasp major factors containing genetic variants of human longevity and healthy aging in DNA repair mechanisms. In summary, this review emphasizes DNA repair activity in human longevity and suggests approach to conduct DNA repair-associated genomic study on human healthy aging.

scholarly journals Genetic Variants of DNA Repair Genes as Predictors of Radiation-Induced Subcutaneous Fibrosis in Oropharyngeal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ankita Gupta ◽  
Don Mathew ◽  
Shabir Ahmad Bhat ◽  
Sushmita Ghoshal ◽  
Arnab Pal
Keyword(s):  
Dna Repair ◽  
Genetic Variants ◽  
Oropharyngeal Carcinoma ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Radical Radiotherapy ◽  
Single Nucleotide ◽  
Radiation Induced ◽  
Repair Genes ◽  
Severe Fibrosis

PurposeTo investigate the impact of genetic variants of DNA repair and pro-fibrotic pathway genes on the severity of radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radical radiotherapy.Materials and MethodsPatients of newly diagnosed squamous cell carcinoma of oropharynx being treated with two-dimensional radical radiotherapy were enrolled in the study. Patients who had undergone surgery or were receiving concurrent chemotherapy were excluded. Patients were followed up at 6 weeks post completion of radiotherapy and every 3 months thereafter for a median of 16 months. Subcutaneous fibrosis was graded according to the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) grading system and the maximum grade was recorded over the length of the patient’s follow-up. Patients with severe fibrosis (≥G3), were compared to patients with minor (≤G2) fibrotic reactions. Eight single nucleotide polymorphisms of 7 DNA repair genes and 2 polymorphisms of a single pro-fibrotic pathway gene were analyzed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and were correlated with the severity of subcutaneous fibrosis.Results179 patients were included in the analysis. Subcutaneous fibrosis was seen in 168 (93.9%) patients. 36 (20.1%) patients had severe (grade 3) fibrosis. On multivariate logistic regression analysis, Homozygous CC genotype of XRCC3 (722C>T, rs861539) (p=0.013*, OR 2.350, 95% CI 1.089-5.382), Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) (p=0.001**, OR 11.626, 95% CI 2.490-275.901) and Homozygous TT genotype of XRCC5 (1401G>T, rs828907) (p=0.020*, OR 2.188, 95% CI 1.652-7.334) were found to be predictive of severe subcutaneous fibrosis. On haplotype analysis, the cumulative risk of developing severe fibrosis was observed in patients carrying both haplotypes of variant Homozygous AA genotype of ERCC4 Ex8 (1244G>A, rs1800067) and Homozygous TT genotype of XRCC5 (1401 G>T, rs828907) (p=0.010*, OR 26.340, 95% CI 4.014-76.568).ConclusionWe demonstrated significant associations between single nucleotide polymorphisms of DNA repair genes and radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radiotherapy. We propose to incorporate these genetic markers into predictive models for identifying patients genetically predisposed to the development of radiation-induced fibrosis, thus guiding personalized treatment protocols.

scholarly journals FOXO Transcriptional Factors and Long-Term Living

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ghulam Murtaza ◽  
Abida Kalsoom Khan ◽  
Rehana Rashid ◽  
Saiqa Muneer ◽  
Syed Muhammad Farid Hasan ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Healthy Aging ◽  
Growth Stress ◽  
Human Longevity ◽  
Growth Factor Signaling ◽  
Forkhead Box ◽  
Foxo Transcription Factors ◽  
Genetic And Environmental Factors

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity.

scholarly journals Premature or pathological aging: longevity

2017 ◽  
Vol 20 (0) ◽  
Author(s):  
Valdemiro Carlos Sgarbieri ◽  
Maria Teresa Bertoldo Pacheco
Keyword(s):  
Quality Of Life ◽  
Literature Review ◽  
Healthy Aging ◽  
Premature Aging ◽  
Human Longevity ◽  
Degenerative Diseases ◽  
Life Conditions ◽  
Main Factors ◽  
Educational Conditions

Abstract The main objective of this literature review was to summarize and characterize the main factors and events that may negatively influence quality of life and human longevity. The factors that act on premature aging processes are essentially the same as those of natural or healthy aging, but in a more intense and uncontrolled manner. Such factors are: 1) genetic (genome); 2) metabolic (metabolome); 3) environmental (life conditions and style, including diet). Factors 1 and 2 are more difficult to control by individuals; once depending on socioeconomic, cultural and educational conditions. Differently of environmental factors that may be totally controlled by individuals. Unfamiliarity with these factors leads to chronic and/or degenerative diseases that compromise quality of life and longevity.

Genetic Variants of DNA Repair Gene XPC Modulating Susceptibility to Cervical Cancer in North India

2009 ◽  
Vol 18 (7) ◽  
pp. 329-335
Author(s):  
Ruchika Gangwar ◽  
Balraj Mittal ◽  
Shruti Srivastava ◽  
Hariom Singh ◽  
Rama Devi Mittal
Keyword(s):  
Cervical Cancer ◽  
Dna Repair ◽  
Genetic Variants ◽  
North India ◽  
Repair Gene ◽  
Dna Repair Gene

scholarly journals Genetic variants linked to education predict longevity

2016 ◽  
Vol 113 (47) ◽  
pp. 13366-13371 ◽  
Author(s):  
Riccardo E. Marioni ◽  
Stuart J. Ritchie ◽  
Peter K. Joshi ◽  
Saskia P. Hagenaars ◽  
Aysu Okbay ◽  
...  
Keyword(s):  
Educational Attainment ◽  
Genetic Variants ◽  
Meta Analysis ◽  
Human Longevity ◽  
Score Distribution ◽  
Generation Scotland ◽  
Profile Score ◽  
Genetic Contributions ◽  
Upper Third ◽  
Lower Mortality Risk

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland,n =∼17,000; UK Biobank,n= ∼115,000; and the Estonian Biobank,n= ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members’ polygenic profile score for education to predict their parents’ longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (totalndeaths= 79,702) and ∼2.4% lower risk for fathers (totalndeaths= 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.

scholarly journals 9p21 and the Genetic Revolution for Coronary Artery Disease

2012 ◽  
Vol 58 (1) ◽  
pp. 104-112 ◽  
Author(s):  
Robert Roberts ◽  
Alexandre F R Stewart
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Genetic Testing ◽  
Coronary Artery ◽  
Genetic Variants ◽  
Genetic Factors ◽  
Genomic Study ◽  
Increased Risk ◽  
Artery Disease

Abstract BACKGROUND It has long been recognized that 50% of the susceptibility for coronary artery disease (CAD) is due to predisposing genetic factors. Comprehensive prevention is likely to require knowledge of these genetic factors. CONTENT Using a genomewide association study (GWAS), the Ottawa Heart Genomic Study and the deCODE group simultaneously identified the first genetic risk variant, at chromosome 9p21. The 9p21 variant became the first risk factor to be identified since 1964. 9p21 occurs in 75% of the population except for African Americans and is associated with a 25% increased risk for CAD with 1 copy and a 50% increased risk with 2 copies. Perhaps the most remarkable finding is that 9p21 is independent of all known risk factors, indicating there are factors contributing to the pathogenesis of CAD that are yet unknown. 9p21 in individuals with premature CAD is associated with a 2-fold increase in risk, similar to that of smoking and cholesterol. Routine genetic testing will probably remain controversial until a specific treatment is developed. Over a period of 5 years, however, GWASs have identified 30 genetic variants for CAD risk, of which only 6 act through the known risk factors. SUMMARY The 9p21 variant has now been established as an independent risk factor for CAD and, along with the additional 29 risk genetic variants recently identified, is likely to provide the thrust for genetic testing and personalized medicine in the near future.

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