It has been a long standing hypothesis that blood tissue of PD Parkinson's disease (PD) patients may exhibit signs of accelerated aging. Here we use DNA methylation based biomarkers of aging ...("epigenetic clock") to assess the aging rate of blood in two ethnically distinct case-control data sets. Using n=508 Caucasian and n=84 Hispanic blood samples, we assess a) the intrinsic epigenetic age acceleration of blood (IEAA), which is independent of blood cell counts, and b) the extrinsic epigenetic age acceleration rate of blood (EEAA) which is associated with age dependent changes in blood cell counts. Blood of PD subjects exhibits increased age acceleration according to both IEAA (p=0.019) and EEAA (p=6.1 x 10(-3)). We find striking differences in imputed blood cell counts between PD cases and controls. Compared to control subjects, PD subjects contains more granulocytes (p=1.0 x 10(-9) in Caucasians, p=0.00066 in Hispanics) but fewer T helper cells (p=1.4 x 10(-6) in Caucasians, p=0.0024 in Hispanics) and fewer B cells (p=1.6 x 10(-5) in Caucasians, p=4.5 x 10(-5) in Hispanics). Overall, this study shows that the epigenetic age of the immune system is significantly increased in PD patients and that granulocytes play a significant role.
Abstract
This commentary focuses on research that has long been at the core of environmental epidemiology: studies of the health effects of air pollution. It highlights publications in the American ...Journal of Epidemiology going back more than 50 years that have contributed to the debate about the validity of this research and its meaning for public policy. Technological advances have greatly expanded the toolbox of environmental epidemiologists in terms of measuring and analyzing complex exposures in large populations. Yet, discussions about biases in estimating air pollution health effects have always been and remain intense. Epidemiologists have brought new methodologies and concepts to this research, alleviating some but not all concerns. Here, the focus is on seminal epidemiologic work that established valid links between air pollution exposures and health outcomes and generated data for environmental policies and prevention. With this commentary, I hope to inspire epidemiologists to address many more of the burning environmental health questions—wildfires included—with a similar scientific doggedness. The rapidly changing conditions of our planet are challenging us to innovate and offer solutions, albeit perhaps a little bit faster this time around.
Epigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women ...consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.
We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue.
Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.
Exposure to ambient air pollution and noise is ubiquitous globally. A strong body of evidence links air pollution, and recently noise, to cardiovascular conditions that eventually may also affect ...cognition in the elderly. Data that support a broader influence of these exposures on cognitive function during aging is just starting to emerge. This review summarizes current findings and discusses methodological challenges and opportunities for research. Although current evidence is still limited, especially for chronic noise exposure, high exposure has been associated with faster cognitive decline either mediated through cerebrovascular events or resulting in Alzheimer's disease. Ambient environmental exposures are chronic and affect large populations. While they may yield relatively modest-sized risks, they nevertheless result in large numbers of cases. Reducing environmental pollution is clearly feasible, though lowering levels requires collective action and long-term policies such as standard setting, often at the national level as well as at the local level.
The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past ...statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution.
It is widely believed that environmental exposures contribute to the vast majority of late-onset sporadic Parkinson's disease (PD), alone or via interactions with genetic factors. The search for ...environmental causes of PD has however been hampered by lack of understanding the prodromal phase of PD development and the difficulties in exposure assessment during this prolonged period. On the other hand, the existence of this prodromal period, along with an increasingly better understanding of PD prodromal symptoms, provides an exciting opportunity to identify environmental factors that initiate PD pathogenesis and/or modify its progression. For prevention efforts, this prodromal stage is of a major interest. Targeting factors that enter the body via the nose or gut has become even more important since the discovery of α-synuclein aggregates in the enteric and olfactory nervous systems. In this paper, we speculate about novel research hypotheses and approaches that may help us better define the role of environment in PD etiology, especially during its extended and complex prodromal phase.
Acetaminophen (paracetamol) is the most commonly used medication for pain and fever during pregnancy in many countries. Research data suggest that acetaminophen is a hormone disruptor, and abnormal ...hormonal exposures in pregnancy may influence fetal brain development.
To evaluate whether prenatal exposure to acetaminophen increases the risk for developing attention-deficit/hyperactivity disorder (ADHD)-like behavioral problems or hyperkinetic disorders (HKDs) in children.
We studied 64,322 live-born children and mothers enrolled in the Danish National Birth Cohort during 1996-2002.
Acetaminophen use during pregnancy was assessed prospectively via 3 computer-assisted telephone interviews during pregnancy and 6 months after child birth.
To ascertain outcome information we used (1) parental reports of behavioral problems in children 7 years of age using the Strengths and Difficulties Questionnaire; (2) retrieved HKD diagnoses from the Danish National Hospital Registry or the Danish Psychiatric Central Registry prior to 2011; and (3) identified ADHD prescriptions (mainly Ritalin) for children from the Danish Prescription Registry. We estimated hazard ratios for receiving an HKD diagnosis or using ADHD medications and risk ratios for behavioral problems in children after prenatal exposure to acetaminophen.
More than half of all mothers reported acetaminophen use while pregnant. Children whose mothers used acetaminophen during pregnancy were at higher risk for receiving a hospital diagnosis of HKD (hazard ratio = 1.37; 95% CI, 1.19-1.59), use of ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44), or having ADHD-like behaviors at age 7 years (risk ratio = 1.13; 95% CI, 1.01-1.27). Stronger associations were observed with use in more than 1 trimester during pregnancy, and exposure response trends were found with increasing frequency of acetaminophen use during gestation for all outcomes (ie, HKD diagnosis, ADHD medication use, and ADHD-like behaviors; P trend < .001). Results did not appear to be confounded by maternal inflammation, infection during pregnancy, the mother's mental health problems, or other potential confounders we evaluated.
Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcome are frequent, these results are of public health relevance but further investigations are needed.
Menopause accelerates biological aging Levine, Morgan E.; Lu, Ake T.; Chen, Brian H. ...
Proceedings of the National Academy of Sciences - PNAS,
08/2016, Letnik:
113, Številka:
33
Journal Article
Recenzirano
Odprti dostop
Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate ...epigenetic biomarker of age (known as the “epigenetic clock”), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women’s Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson’s disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790). We find that increased epigenetic age acceleration in blood is significantly associated with earlier menopause (P = 0.00091), bilateral oophorectomy (P = 0.0018), and a longer time since menopause (P = 0.017). Conversely, epigenetic age acceleration in buccal epithelium and saliva do not relate to age at menopause; however, a higher epigenetic age in saliva is exhibited in women who undergo bilateral oophorectomy (P = 0.0079), while a lower epigenetic age in buccal epithelium was found for women who underwent menopausal hormone therapy (P = 0.00078). Using genetic data, we find evidence of coheritability between age at menopause and epigenetic age acceleration in blood. Using Mendelian randomization analysis, we find that two SNPs that are highly associated with age at menopause exhibit a significant association with epigenetic age acceleration. Overall, our Mendelian randomization approach and other lines of evidence suggest that menopause accelerates epigenetic aging of blood, but mechanistic studies will be needed to dissect cause-and-effect relationships further.
Recently, many new approaches, study designs, and statistical and analytical methods have emerged for studying gene-environment interactions (G×Es) in large-scale studies of human populations. There ...are opportunities in this field, particularly with respect to the incorporation of -omics and next-generation sequencing data and continual improvement in measures of environmental exposures implicated in complex disease outcomes. In a workshop called "Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases," held October 17-18, 2014, by the National Institute of Environmental Health Sciences and the National Cancer Institute in conjunction with the annual American Society of Human Genetics meeting, participants explored new approaches and tools that have been developed in recent years for G×E discovery. This paper highlights current and critical issues and themes in G×E research that need additional consideration, including the improved data analytical methods, environmental exposure assessment, and incorporation of functional data and annotations.
The prevalence of autistic disorder (AD), a serious developmental condition, has risen dramatically over the past two decades, but high-quality population-based research addressing etiology is ...limited.
We studied the influence of exposures to traffic-related air pollution during pregnancy on the development of autism using data from air monitoring stations and a land use regression (LUR) model to estimate exposures.
Children of mothers who gave birth in Los Angeles, California, who were diagnosed with a primary AD diagnosis at 3-5 years of age during 1998-2009 were identified through the California Department of Developmental Services and linked to 1995-2006 California birth certificates. For 7,603 children with autism and 10 controls per case matched by sex, birth year, and minimum gestational age, birth addresses were mapped and linked to the nearest air monitoring station and a LUR model. We used conditional logistic regression, adjusting for maternal and perinatal characteristics including indicators of SES.
Per interquartile range (IQR) increase, we estimated a 12-15% relative increase in odds of autism for ozone odds ratio (OR) = 1.12, 95% CI: 1.06, 1.19; per 11.54-ppb increase and particulate matter ≤ 2.5 µm (OR = 1.15; 95% CI: 1.06, 1.24; per 4.68-μg/m3 increase) when mutually adjusting for both pollutants. Furthermore, we estimated 3-9% relative increases in odds per IQR increase for LUR-based nitric oxide and nitrogen dioxide exposure estimates. LUR-based associations were strongest for children of mothers with less than a high school education.
Measured and estimated exposures from ambient pollutant monitors and LUR model suggest associations between autism and prenatal air pollution exposure, mostly related to traffic sources.
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