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.
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.
When an electron moves in a smoothly varying non-collinear magnetic structure, its spin orientation adapts constantly, thereby inducing forces that act both on the magnetic structure and on the ...electron. These forces may be described by electric and magnetic fields of an emergent electrodynamics1, 2, 3, 4. The topologically quantized winding number of so-called skyrmions--a type of magnetic whirl discovered recently in chiral magnets5, 6, 7--has been predicted to induce exactly one quantum of emergent magnetic flux per skyrmion. A moving skyrmion is therefore expected to induce an emergent electric field following Faraday's law of induction, which inherits this topological quantization8. Here we report Hall-effect measurements that establish quantitatively the predicted emergent electrodynamics. We obtain quantitative evidence for the depinning of skyrmions from impurities (at current densities of only 106 A m-2) and their subsequent motion. The combination of exceptionally small current densities and simple transport measurements offers fundamental insights into the connection between the emergent and real electrodynamics of skyrmions in chiral magnets, and might, in the long term, be important for applications. PUBLICATION ABSTRACT
Fermi liquid theory provides a remarkably powerful framework for the description of the conduction electrons in metals and their ordering phenomena, such as superconductivity, ferromagnetism, and ...spin- and charge-density-wave order. A different class of ordering phenomena of great interest concerns spin configurations that are topologically protected, that is, their topology can be destroyed only by forcing the average magnetization locally to zero. Examples of such configurations are hedgehogs (points at which all spins are either pointing inwards or outwards) and vortices. A central question concerns the nature of the metallic state in the presence of such topologically distinct spin textures. Here we report a high-pressure study of the metallic state at the border of the skyrmion lattice in MnSi, which represents a new form of magnetic order composed of topologically non-trivial vortices. When long-range magnetic order is suppressed under pressure, the key characteristic of the skyrmion lattice--that is, the topological Hall signal due to the emergent magnetic flux associated with the topological winding--is unaffected in sign or magnitude and becomes an important characteristic of the metallic state. The regime of the topological Hall signal in temperature, pressure and magnetic field coincides thereby with the exceptionally extended regime of a pronounced non-Fermi-liquid resistivity. The observation of this topological Hall signal in the regime of the NFL resistivity suggests empirically that spin correlations with non-trivial topological character may drive a breakdown of Fermi liquid theory in pure metals.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
We report detailed low-temperature magnetotransport and magnetization measurements in MnSi under pressures up to ~ 12 kbar. Tracking the role of sample quality, pressure transmitter, and field and ...temperature history allows us to link the emergence of a giant topological Hall resistivity ~50 nOmega cm to the skyrmion lattice phase at ambient pressure. We show that the remarkably large size of the topological Hall resistivity in the zero-temperature limit must be generic. We discuss various mechanisms which can lead to the much smaller signal at elevated temperatures observed at ambient pressure.
Recent small angle neutron scattering suggests that the spin structure in the A phase of MnSi is a so-called triple-Q state, i.e., a superposition of three helices under 120 degrees. Model ...calculations indicate that this structure in fact is a lattice of so-called Skyrmions, i.e., a lattice of topologically stable knots in the spin structure. We report a distinct additional contribution to the Hall effect in the temperature and magnetic field range of the proposed Skyrmion lattice, where such a contribution is neither seen nor expected for a normal helical state. Our Hall effect measurements constitute a direct observation of a topologically quantized Berry phase that identifies the spin structure seen in neutron scattering as the proposed Skyrmion lattice.
At the start of the postgenomics era, most Parkinson’s disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored ...gene–environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, and occupational use) in a large population-based case–control study of incident PD in central California. Specifically, we assessed interactions with genes responsible for pesticide metabolism (
PON1
); transport across the blood–brain barrier (
ABCB1
); pesticides interfering with or depending on dopamine transporter activity (
DAT
/
SLC6A3
) and dopamine metabolism (
ALDH2
); impacting mitochondrial function via oxidative/nitrosative stress (
NOS1
) or proteasome inhibition (
SKP1
); and contributing to immune dysregulation (
HLA-DR
). These studies established some specificity for pesticides’ neurodegenerative actions, contributed biologic plausibility to epidemiologic findings, and identified genetically susceptible populations.
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.
High pressure studies in MnSi suggest the existence of a non-Fermi liquid state without quantum criticality. The observation of partial magnetic order in a small pocket of the pressure versus ...temperature phase diagram of MnSi has additionally inspired several proposals of complex spin textures in chiral magnets. We used neutron scattering to observe the formation of a two-dimensional lattice of skyrmion lines, a type of magnetic vortices, under applied magnetic fields in metallic and semiconducting B20 compounds. In strongly disordered systems the skyrmion lattice is hysteretic and extends over a large temperature range. Our study experimentally establishes magnetic materials lacking inversion symmetry as an arena for new forms of spin order composed of topologically stable spin textures.
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