scholarly journals The beginnings of Alzheimer’s disease: A review on inflammatory, mitochondrial, genetic and epigenetic pathways

Genetika ◽  
2016 ◽  
Vol 48 (2) ◽  
pp. 515-524
Author(s):  
Simone Perna ◽  
Chiara Bologna ◽  
Pietro Cavagna ◽  
Luisa Bernardinelli ◽  
Davide Guido ◽  
...  
Keyword(s):  
Risk Factors ◽  
Amyloid Beta Protein ◽  
Case Control Studies ◽  
Direct Role ◽  
Mtdna Haplogroups ◽  
Multifactorial Diseases ◽  
Age Related ◽  
Apolipoprotein E Gene ◽  
Genes Encoding

Alzheimer?s Disease (AD) is the most common cause of sporadic dementia, as it affects 60% of cognitive impaired patients; it commonly affects middle and late life, and it is considered an age-related disease. Early-onset familial AD is associated with mutations of the genes encoding amyloid precursor protein (APP), presenilin 1 (PS-1), or PS-2, resulting in the overproduction of amyloid beta-protein. Epidemiological and case-control studies have led to the identification of several risk factors for sporadic AD. The most concrete genetic risk factor for AD is the epsilon4 allele of apolipoprotein E gene (APOE). In addition, several genes such as CTNNA3, GAB2, PVRL2, TOMM40, and APOC1 are known to be the risk factors that contribute to AD pathogenesis. A direct role of interaction between genetic and environmental determinants has been proposed in an epigenetic dynamic for environmental factors operating during the preconceptual, fetal and infant phases of life. Also the the association between mtDNA inherited variants and multifactorial diseases and AD has been investigated by a number of studies that, however, didn?t reach a general consensus on the correlation between mtDNA haplogroups and AD.

scholarly journals Association between Risk Factors for Vascular Dementia and Adiponectin

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Juhyun Song ◽  
Won Taek Lee ◽  
Kyung Ah Park ◽  
Jong Eun Lee
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Signal Transduction ◽  
Vascular Dementia ◽  
Case Control ◽  
Case Control Studies ◽  
Insulin Signal Transduction ◽  
Increased Risk ◽  
The Brain

Vascular dementia is caused by various factors, including increased age, diabetes, hypertension, atherosclerosis, and stroke. Adiponectin is an adipokine secreted by adipose tissue. Adiponectin is widely known as a regulating factor related to cardiovascular disease and diabetes. Adiponectin plasma levels decrease with age. Decreased adiponectin increases the risk of cardiovascular disease and diabetes. Adiponectin improves hypertension and atherosclerosis by acting as a vasodilator and antiatherogenic factor. Moreover, adiponectin is involved in cognitive dysfunction via modulation of insulin signal transduction in the brain. Case-control studies demonstrate the association between low adiponectin and increased risk of stroke, hypertension, and diabetes. This review summarizes the recent findings on the association between risk factors for vascular dementia and adiponectin. To emphasize this relationship, we will discuss the importance of research regarding the role of adiponectin in vascular dementia.

scholarly journals Risk Factors for Age-Related Maculopathy

2009 ◽  
Vol 2009 ◽  
pp. 1-39 ◽  
Author(s):  
Paul P. Connell ◽  
Pearse A. Keane ◽  
Evelyn C. O'Neill ◽  
Rasha W. Altaie ◽  
Edward Loane ◽  
...  
Keyword(s):  
Risk Factors ◽  
Epidemiologic Study ◽  
Case Series ◽  
The Elderly ◽  
Factor H ◽  
Environment Interaction ◽  
Complement Factor ◽  
Case Control Studies ◽  
Cross Sectional ◽  
Age Related

Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

scholarly journals Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1351 ◽  
Author(s):  
Luca Rinaldi ◽  
Riccardo Nevola ◽  
Gianluigi Franci ◽  
Alessandro Perrella ◽  
Giusy Corvino ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Immune Surveillance ◽  
Liver Stiffness ◽  
Virologic Response ◽  
Direct Acting Antivirals ◽  
Direct Role ◽  
Direct Acting ◽  
The Impact

Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.

scholarly journals New Insights into the Epidemiology of Vulvar Cancer: Systematic Literature Review for an Update of Incidence and Risk Factors

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 389
Author(s):  
Lauro Bucchi ◽  
Margherita Pizzato ◽  
Stefano Rosso ◽  
Stefano Ferretti
Keyword(s):  
Risk Factors ◽  
Cancer Incidence ◽  
Vulvar Cancer ◽  
Lichen Sclerosus ◽  
Intraepithelial Neoplasia ◽  
Incidence Rates ◽  
Vulvar Intraepithelial Neoplasia ◽  
Case Control Studies ◽  
Original Cohort

The aim of this review was an update of vulvar cancer incidence rates and trends and of all known and putative risk factors for the disease. The most recent incidence data were sought from official sources (WHO Cancer Incidence in Five Continents). To obtain an estimate of time trends in some areas, we compared data from Cancer Incidence in Five Continents with the few available studies that measured incidence using comparable methods. With respect to risk factors, a systematic PubMed search identified 1585 relevant articles published between 1980 and 2021. Abstracts and full texts were screened. Sixty-nine eligible original cohort and case-control studies were selected. Information was extracted using a PRISMA predesigned form. Nineteen risk factors, or risk factor categories, were investigated by two or more original studies. Solitary, unreplicated studies addressed the putative role of eight more factors. Recent advances have provided further evidence supporting the carcinogenic model centred on human papillomavirus infection with different defects of the immune function. Conversely, the model centred on the role of vulvar lichen sclerosus and the often associated differentiated vulvar intraepithelial neoplasia has continued to be epidemiologically understudied. More research on the association between these two conditions and vulvar cancer is a priority.

Age and gender characteristics of indicators of systemic endotoxinemia and their relationship with generally accepted laboratory risk factors for atherosclerosis

2019 ◽  
pp. 13-19
Author(s):  
Д.П. Покусаева ◽  
И.А. Аниховская ◽  
Л.А. Коробкова ◽  
М.Ю. Яковлев
Keyword(s):  
Risk Factors ◽  
Gender Differences ◽  
Lipid Profile ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Age Dynamics ◽  
Age Related ◽  
Systemic Endotoxemia

В последние годы большое внимание уделяется роли микробиоты в атерогенезе с позиций воспалительной теории. На основании экспериментальных и клинических данных была сформулирована эндотоксиновая теория атеросклероза. Подтверждением важной роли кишечного липополисахарида в атерогенезе является возрастная динамика показателей системной эндотоксинеми и липидного профиля. Цель исследования - выявление взаимосвязи между показателями системной эндотоксинемии и факторами риска атеросклероза, в аспекте возрастных и гендерных различий. Методика. Обследовано 113 пациентов среднего возраста. Все пациенты прошли оценку факторов риска развития атеросклероза по шкале SCORE. Пациенты были отнесены к средней группе риска (до 5%), оценивали себя как «здоровые», жалоб на момент обследования не предъявляли. Индекс массы тела был до 30 кг/м2. Определялись показатели липидного профиля (анализатор «StatFax 3300», США, реактивы «Analyticon», Германия): уровень общего холестерина, липопротеинов высокой плотности и уровень триглицеридов, рассчитывался индекс атерогенности и концентрация липопротеинов низкой плотности. Определялись параметры системной эндотоксинемии: концентрации липополисахарида (микро-ЛАЛ-тест), уровень антител к гидрофобной и гидрофильной частям молекулы ЛПС методом «СОИС-ИФА». Результаты. Выявлена прямая значимая корреляция концентрации общего холестерина, липопротеинов низкой плотности и липопротеинов высокой плотности в зависимости от возраста. При построении регрессионной модели зависимости показателей системной эндотоксинемии от пола и возраста пациентов не выявлено. При визуальной оценке графиков обращает внимание наличие у женщин тенденции к возрастному повышению уровня липополисахарида и снижению концентрации антител к гидрофильной части молекулы липополисахарида. Обнаружены гендерные различия показателей липидного профиля и уровня липополисахарида. Заключение. Статистически значимая возрастная динамика показателей липидного профиля при тенденции к нарастанию уровня липополисахарида, а также снижение концентрации антител к гидрофильной части молекула липополисахарида, имеющее определённые гендерные различия, свидетельствует о целесообразности продолжения исследований с увеличением числа обследованных в расширенном возрастном диапазоне. Atherosclerosis is a polyetiologic disease. In recent years, much attention has been paid to the role of the microbiota in atherogenesis from the perspective of inflammatory theory. Based on experimental and clinical data, the endotoxin theory of atherosclerosis was formulated. Confirmation of the important role of intestinal lipopolysaccharide in atherogenesis is the age dynamics of systemic endotoxemia parametrs and lipid profile. The goal of our study was to identify the relationship between the indicators of systemic endotoxemia and the generally accepted risk factors for atherosclerosis, especially the age dynamics and the influence of gender. Methods. We examined 113 patients middle age. All patients were assessed for risk factors for atherosclerosis according to the SCORE scale. Patients were assigned to the average risk group (up to 5%), rated themselves as “healthy”, did not present any complaints at the time of the survey. The body mass index was up to 30 kg/m2. Indicators of the lipid profile were determined («StatFax» 3300 analyzer, USA, «Analyticon» reagents, Germany): the level of total cholesterol, high-density lipoprotein and triglyceride levels, the atherogenic index and the concentration of low-density lipoprotein were calculated. The parameters of systemic endotoxemia were determined: the concentration of lipopolysaccharide using a micro-LAL test, the level of antibodies to the hydrophobic and hydrophilic parts of the lipopolysaccharide molecule using the “SOIS-ELISA” method. Results. A direct significant correlation was found between the concentration of total cholesterol, low-density lipoprotein and high-density lipoprotein, depending on age. When constructing a regression model of the age dynamics, the concentrations of lipopolysaccharides, antibodies to the hydrophobic and hydrophilic parts of the lipopolysaccharide molecule were not detected (p> 0.05). When adjusted for gender, the age dynamics of systemic endotoxemia was also not observed. When visually assessing the graphs, attention is drawn to the fact that women have an age-related tendency to increase the level of lipopolysaccharide and a decrease in the concentration of antibodies to the hydrophilic part of the lipopolysaccharide molecule. In addition, gender differences in lipid profile and lipopolysaccharide levels were found. Conclusion. The significant age-related dynamics of the lipid profile in the presence of a tendency to an increase in the level of lipopolysaccharide and a decrease in the concentration of antibodies to the hydrophilic part of the lipopolysaccharide molecule, which has certain gender differences, revealed the necessity and feasibility of continuing research with an increase in the number of subjects and in the extended age range.

scholarly journals Brain deep medullary veins on 3-T MRI in a population-based cohort

2020 ◽  
pp. 0271678X2091846
Author(s):  
Dong-Hui Ao ◽  
Ding-Ding Zhang ◽  
Fei-Fei Zhai ◽  
Jiang-Tao Zhang ◽  
Fei Han ◽  
...  
Keyword(s):  
Risk Factors ◽  
Brain Atrophy ◽  
Small Vessel Disease ◽  
Population Based ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Neurodegenerative Process ◽  
Age Related ◽  
Deep Medullary Veins

Our aim is to investigate whether vascular risk factors are associated with cerebral deep medullary veins (DMVs) and whether DMVs are associated with MRI markers of cerebral small vessel disease (CSVD) or risk of stroke. In a community-based cohort of 1056 participants (mean age 55.7 years), DMVs were identified on susceptibility-weighted imaging (SWI) and counted in periventricular regions. Neuroimaging markers including lacunes, whiter matter hyperintensity (WMH), microbleeds, enlarged perivascular space, and brain atrophy were evaluated. The number of DMVs decreased with age (p = 0.007). After adjusting for age and sex, the number of DMVs was not associated with traditional vascular risk factors. Fewer DMVs was associated with increase of WMH and lacunes, but the association vanished after adjustment for vascular risk factors. However, fewer DMVs were independently associated with brain atrophy (p < 0.001). DMVs were not associated with three-year risk of stroke. Our results suggest that DMV is significantly different from other MRI markers of CSVD regarding risk factors, association with other CSVD markers, and risk of stroke. Nonetheless, the significant association between DMV and brain atrophy suggested the potential role of venules in age-related neurodegenerative process, which deserves further investigation.

scholarly journals Determining the Role of ApoE4 in Age-Related Cerebrovascular Decline

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 118-119
Author(s):  
Kate Foley ◽  
Peter Borchian ◽  
Dylan Garceau ◽  
Kevin Kotredes ◽  
Paul Territo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Transcriptional Profiling ◽  
Genetic Risk Factors ◽  
Expression Of Genes ◽  
Age Related ◽  
Age Dependent ◽  
Cerebrovascular Health ◽  
E4 Allele

Abstract Cerebrovascular decline occurs during aging and may be critical during prodromal phases of Alzheimer’s disease (AD). The E4 allele of apolipoprotein E (APOE4) is the greatest genetic risk factor for AD and decreased longevity and studies suggest APOE4 increases risk for age-dependent cerebrovascular damage. To study the relationship between APOE4 and age-related cerebrovascular decline, male and female C57BL/6J (B6) mice carrying combinations of APOE alleles including APOE4 (risk) and APOE3 (neutral), as well as B6 controls were assessed at a variety of ages from 4 to 24 mos for cognitive ability, biometrics and cerebrovascular health including i) PET/MRI using 64Cu-PTSM (perfusion) and 18F-FDG (metabolism), ii) transcriptional profiling and iii) immunofluorescence. Despite no cognitive decline, male APOE4 mice showed hypo-perfusion and hypo-metabolism by 12 mos, while female APOE4 mice showed an uncoupled hyper-perfusion and hypo-metabolism phenotype. Transcriptional profiling showed differential expression of genes involved in regulation of cerebral perfusion, glucose transportation and metabolism in APOE4 mice. An age-dependent blood brain barrier compromise was also apparent in the brains of female APOE4 mice. Physical activity reduces risk for human AD and our data shows exercise improves cerebrovascular health in mice. However, the effects to cerebrovascular health in individuals carrying genetic risk factors such as APOE4 are not known. To determine whether exercise can overcome APOE4-dependent cerebrovascular damage, APOE mice are being exercised from 2-4 and to 2-12 mos. Transcriptional profiling and immunofluorescence will determine whether the benefits of exercise to the cerebrovasculature are modulated by genetic risk factors such as APOE4.

scholarly journals FoxO1 Is a Novel Regulator of 20S Proteasome Subunits Expression and Activity

2021 ◽  
Vol 9 ◽  
Author(s):  
Marianna Kapetanou ◽  
Tobias Nespital ◽  
Luke S. Tain ◽  
Andre Pahl ◽  
Linda Partridge ◽  
...  
Keyword(s):  
Proteasome Activity ◽  
20S Proteasome ◽  
Direct Role ◽  
Forkhead Box ◽  
Age Related ◽  
Proteasome Subunits ◽  
Rate Limiting

Proteostasis collapses during aging resulting, among other things, in the accumulation of damaged and aggregated proteins. The proteasome is the main cellular proteolytic system and plays a fundamental role in the maintenance of protein homeostasis. Our previous work has demonstrated that senescence and aging are related to a decline in proteasome content and activities, while its activation extends lifespan in vitro and in vivo in various species. However, the mechanisms underlying this age-related decline of proteasome function and the down-regulation in expression of its subunits remain largely unclear. Here, we demonstrate that the Forkhead box-O1 (FoxO1) transcription factor directly regulates the expression of a 20S proteasome catalytic subunit and, hence, proteasome activity. Specifically, we demonstrate that knockout of FoxO1, but not of FoxO3, in mice severely impairs proteasome activity in several tissues, while depletion of IRS1 enhances proteasome function. Importantly, we show that FoxO1 directly binds on the promoter region of the rate-limiting catalytic β5 proteasome subunit to regulate its expression. In summary, this study reveals the direct role of FoxO factors in the regulation of proteasome function and provides new insight into how FoxOs affect proteostasis and, in turn, longevity.

Role of polyphenols in the prevention of immunoinflammatory diseases

2021 ◽  
Author(s):  
Dominique Delmas
Keyword(s):  
Interleukin 6 ◽  
Inflammatory Diseases ◽  
Potential Effect ◽  
Sirtuin 1 ◽  
Main Role ◽  
Nuclear Factor ◽  
Age Related ◽  
Genes Encoding ◽  
Different Origins

Inflammation has been described as an initiator event of major diseases with significant impact in terms of public health such as cardiovascular diseases, autoimmune diseases, eye diseases, age-related diseases and more particularly neurodegenerative diseases, or the occurrence and development of cancers. Among the microcomponents of the diet which can participate in a prevention of inflammation and subsequently to various associated diseases, polyphenols from different origins such as resveratrol, could be good candidates. Indeed, in this presentation, we highlight the potential effect of polyphenol on both interleukins secretion by pro-inflammatory lymphocytes Th17 and on the lymphocyte differentiation. In this process, we demonstrate the main role of the NAD-dependent deacetylase, Sirtuin 1 and of the nuclear factor STAT3. T lymphocytes that are not only the cells where the STAT3 factor plays an important role, it is also the case of macrophages where this nuclear factor makes it possible to activate the transcription of genes encoding pro-inflammatory interleukins such as interleukin-6 and -8. Furthermore, macrophages are also able to produce interleukin-1β from an inflammatory complex namely inflammasome. In this way, polyphenols could reduce interleukin-6 level thus down regulates STAT3 activation in macrophages, leading to the impairment of the running inflammatory amplification loop between macrophages and chondrocytes and subsequently could reduce some inflammatory diseases such as arthritis.

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