scholarly journals Comprehensive longitudinal study of epigenetic mutations in aging

2019 ◽  
Author(s):  
Yunzhang Wang ◽  
Robert Karlsson ◽  
Juulia Jylhävä ◽  
Åsa K. Hedman ◽  
Catarina Almqvist ◽  
...  

AbstractBackgroundThe role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.ResultsWe verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.ConclusionsHere we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunzhang Wang ◽  
Robert Karlsson ◽  
Juulia Jylhävä ◽  
Åsa K. Hedman ◽  
Catarina Almqvist ◽  
...  

Abstract Background The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages. Results We verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis, and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects. Conclusions Here we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.


Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1726-1730
Author(s):  
KA Melez ◽  
LF Fries ◽  
BS Bender ◽  
T Quinn ◽  
MM Frank

Decreased immune functions have been suggested as a cause for the increased incidence of autoimmunity, malignancy, and infection in the elderly population. To assess the possible role of changes in macrophage function in the aging process we studied the Fc receptor- mediated clearance of IgG-coated erythrocytes in 56 healthy normal volunteers by following the removal of radiolabeled autologous erythrocytes. An age-related decrease in Fc-mediated clearance rates in both female and male subjects was found, which suggests a physiological decline of this macrophage function in older individuals.


2015 ◽  
Vol 8 (4) ◽  
pp. 30-39
Author(s):  
Svetlana Georgievna Belekhova ◽  
Yury Sergeevich Astakhov

The article presents a review of studies dedicated to the role of genetic factors in age-related macular degeneration (AMD) pathogenesis. The polymorphisms of Y402H gene of the complement factor Н, HTRA1, ARMS2/LOC387715, and PLEKHA1 increase the risk of AMD development. More detailed description is done also for other genes, involved into this disease, which were identified so far. Possible schemes of influence of mutations in these genes on AMD development and progression


Author(s):  
Raphaele Tsao ◽  
Cecile Kindelberger ◽  
Benedicte Fréminville ◽  
Renaud Touraine ◽  
Gerald Bussy

Abstract The aim of this cross-sectional study was to analyze the typical aging process in adults with Down syndrome, focusing on its variability. The sample comprised 120 adults with Down syndrome who were free of dementia. Ages ranged from 20 to 69 years. Each participant was assessed on cognitive functioning and social adaptation, and was checked for the presence of psychopathological disorders. Results revealed an age-related deterioration in both cognitive and social adaptation skills, the extent of this decline depending on the dimension under scrutiny, and interindividual variability in aging profiles.


1997 ◽  
Vol 69 (3) ◽  
pp. 183-195 ◽  
Author(s):  
A. G. NIKITIN ◽  
R. J. SHMOOKLER REIS

Genetic instability is associated with aging in many species. One of the initiating factors for genetic instability is the movement of transposable elements (TEs), which occur in all prokaryotic and eukaryotic organisms. The hypothesis that TEs could be involved in the aging process is discussed and the correlation between aging and activity of TEs is analysed in a variety of biological systems.


Author(s):  
Tania Rescigno ◽  
Mario F. Tecce ◽  
Anna Capasso

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.


2021 ◽  
Vol 15 (10) ◽  
pp. 2643-2646
Author(s):  
Shabnam Khan ◽  
Bushra Wasim Khan ◽  
Madeeha Sadiq ◽  
Fawad Rizvi ◽  
Faraz Ahmed Baig ◽  
...  

Aim: Comparative immunohistochemical study of expression of α A Crystallin in non-cataract lenses and age-related cataract lenses in humans. Methodology: This was an observational cross sectional study. There are two groups in this study. Group A comprised of 121 senile degenerative cataract lenses from diagnosed patients. Group B included of 10 non-cataract lenses from patients who underwent surgeries for enucleation due to trauma and retinoblastoma. Lenses were fixed in 10% Buffered Neutral Formalin and processed to make paraffin blocks. Immunohistochemistry (IHC) staining was performed on sections using primary antibody for α A crystallin. Data was analyzed through SPSS software version 24. Results: Immunohistochemical staining of group A showed 80.2% Strong Positive expression while 19.8% showed Intermediate Positive expression of α A Crystallin. 100% Strong Positive expression of α A Crystallin was seen in group B. Comparison of expression of α A Crystallin in two groups showed significant decrease (p<0.001) in expression. Conclusion: Decreased expression of α A Crystallin in IHC stained senile cataract lens indicates the role of structural alterations of lens fibers in pathogenesis of senile cataract. If mechanism involved in causing these alterations can be identified and targeted so that progression of senile cataract may be delayed. Keywords: Immunohistochemistry, α A crystallin expression, senile cataract, Human eye Lens, Lens Fiber.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Andreas Waldner ◽  
Sarah Dassati ◽  
Bernhard Redl ◽  
Nicola Smania ◽  
Marialuisa Gandolfi

Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an important role in several neurodegenerative diseases. ApoD is expressed in and secreted from a variety of peripheral and brain tissues. Increments of ApoD have been reported in relation with oxidative stress conditions, aging, and degeneration in the nervous system. Preliminary findings support the role of ApoD in neuroprotection. However, its role in PD remains unclear. To date, no studies have been performed on the relationship between ApoD in the blood and PD, as neurodegenerative pathology related to oxidative damage. We investigated the concentration of ApoD in the blood of healthy control subjects and PD patients with mild-to-moderate neurological impairment. ApoD plasma levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA) in 90 healthy subjects (aging-analysis cohort) and in 66 PD patients at different stages compared with 19 age-matched healthy subjects. Significant age-related increase of ApoD was detected in subjects older than 65 years of age (p<0.002). In PD patients, a significant increase in ApoD plasma concentration was found compared with healthy subjects of the same age (p<0.05). ApoD and PD stage are significantly correlated (p<0.05). ApoD might be a valid marker for the progression of PD.


Reumatismo ◽  
2020 ◽  
Vol 72 (1) ◽  
pp. 31-43 ◽  
Author(s):  
L. Punzi ◽  
G. Medea

The objective was to assess knowledge and therapeutic approaches to the management of gout among healthcare professionals and people with/without gout, in Italy. This was a cross-sectional internet-based survey targeting general practitioners (GPs), specialists, pharmacists, and people with/without gout. Between December 2017 and March 2018, participants completed questionnaires on epidemiology, cause/risk factors, therapy objectives and management/treatment strategies to improve outcomes. Overall, 3184 people completed the survey: 699 GPs, 426 specialists, 655 pharmacists and 1404 subjects from the general population: 126 (9.0%) with and 1278 (91.0%) without gout. Notably, less than half of GPs, specialists and people without gout confirmed the published 1% prevalence of gout in Italy. Lifestyle was acknowledged as the main risk factor for gout by nearly 50% of specialists and GPs, while only 13.8% and 12.4%, respectively, considered the role of genetic factors. Uric acid overproduction was deemed as the cause of gout by 60% of GPs and specialists, whereas insufficient excretion by only 30%. Fewer than half of patients were aware that gout permanently damages joints, and even fewer of the renal and cardiovascular implications (19.4% and 12%, respectively); moreover, most people without gout replied that their doctor had never talked with them about uric acid and its correlation with gout development. Finally, GPs were divided on uric acid target levels (48.3% said <6 mg/dL and 18.9% <7 mg/dL). Despite major advances in the knowledge of physiopathological mechanisms of gout, the results of our survey highlight the many treatment and knowledge gaps in its management. Cooperation between multidisciplinary teams is required to break down barriers and ensure optimal treatment with effective and innovative agents of this ever-increasing debilitating condition.


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