Ilja Demuth

Ilja Demuth
Charité Universitätsmedizin Berlin | Charité · Department of Endocrinology and Metabolic Diseases

Professor

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333
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Publications

Publications (333)
Article
The current study examined cross-sectional and longitudinal associations between nocturia and frailty in a cohort of men and women aged 60 years and older, as evidence on this topic was lacking. We analyzed baseline and follow-up data (n = 1671) from the Berlin Aging Study II (BASE-II), a prospective longitudinal cohort study focusing on the factor...
Article
Low body weight and especially unwanted weight loss were shown to be associated with higher mortality in older adults. Change in body weight was reported to be one of the unintended side effects of lockdown measures that were put in place to combat the COVID-19 pandemic. In this study, we first describe weight change in 472 participants (mean age:...
Article
Several markers are available that aim at the quantification of inter-individual differences in biological age. While many of these markers have been evaluated individually, there are few comparisons in terms of their association with age-related outcomes within the same dataset available. In this study, we compare 13 different aging markers in rel...
Article
Low levels of selenium in blood were shown to be associated with adverse health outcomes and are discussed as anti-aging interventions by some investigators. Inter-individual differences in the aging process can be quantified by epigenetic clocks (DNA methylation age, DNAmA). In this study, we analyzed 1,568 participants of the Berlin Aging Study I...
Article
The metabolic syndrome (MetS) is highly prevalent in the general population and associated with increased morbidity and mortality. Its diagnosis is based on cut-off values for five cardiovascular risk factors, three of which must be met to make the diagnosis. Epigenetic clocks (Horvath, GrimAge) can be used to quantify differences in biological age...
Article
Full-text available
The immune system likely plays a key role in Parkinson’s disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for P...
Preprint
Importance Data on the capacity of more recently developed epigenetic age measures to predict a future onset of Metabolic Syndrome (MetS) are lacking. Objective The aim of the study was a comparative analysis of different DNA methylation (DNAm)-based epigenetic clocks with regard to their ability to predict a future onset of MetS. In addition, cro...
Preprint
Background Beyond their essential roles in regulating reproduction and development, sex hormones play a crucial role in the aging processes. Observational studies have indicated that low sex hormone concentrations in older age are associated with adverse health events. DNA methylation age acceleration (DNAmAA) estimated from epigenetic clocks quant...
Preprint
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Background: The immune system plays a crucial role in the pathogenesis of neurodegenerative diseases. Here, we explored whether blood immune cell profiles are already altered in healthy individuals with a genetic predisposition to amyotrophic lateral sclerosis (ALS) or Alzheimer's disease (AD). Methods: Using multicolor flow cytometry, we analyzed...
Preprint
Full-text available
The immune system likely plays a key role in Parkinson's disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for P...
Article
Aging is a complex process influenced by mechanisms operating at numerous levels of functioning. Multiple biomarkers of age have been identified, yet we know little about how the different alternative age indicators are intertwined. In the Berlin Aging Study II (nmin= 328; nmax= 1,517, women = 51%; 14.27 years of education), we examined how levels...
Preprint
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Background & Aim The current study examined cross-sectional and longitudinal associations between nocturia and frailty in a cohort of men and women aged 60 years and older, as evidence on this topic was lacking. Methods Baseline and follow-up data from the Berlin Aging Study II (n=1671) assessed on average 7.1 (IQR 6.2-8.7) years apart were analyze...
Article
Full-text available
INTRODUCTION The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood‐derived DNA methylation as a promising tool for early dementia risk detection. METHODS In conjunction with an extensive array of machine learning...
Article
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While numerous studies have confirmed a causal association between lipoprotein(a) [Lp(a)] and cardiovascular diseases, only a few studies have assessed the relationship between Lp(a) and pulmonary health, with inconsistent findings regarding this topic. This study’s aim was to examine whether levels of serum Lp(a) are associated with lung function...
Preprint
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Aging is a fundamental risk factor for a wide array of diseases. The Berlin Aging Study II (BASE-II) is a cohort study designed to investigate the physical, mental, and social determinants of successful aging. We utilized high-throughput mass spectrometry to measure the proteomes of 1890 BASE-II participants, divided into two age groups: 27-37 year...
Preprint
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Background The microbially generated amino acid-derived metabolite imidazole propionate (ImP) contributes to the pathogenesis of type 2 diabetes. However, the effect of ImP on endothelial cell physiology and its role in atherosclerotic coronary artery disease (CAD) is unknown. Using both human and animal model studies, we investigated the potential...
Article
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To check claims of a “loneliness epidemic,” we examined whether current cohorts of older adults report higher levels and/or steeper age-related increases in loneliness than earlier-born peers. Specifically, we used 1,068 age-matched longitudinal reports (Mage observations = 79 years, 49% women) of loneliness provided by independent samples recruite...
Preprint
Full-text available
Introduction Biological age reflects inter-individual differences in biological function and capacity beyond chronological age. Biological age can be estimated by DNA methylation age (DNAmA) and its deviation from chronological age, DNAmA acceleration (DNAmAA). Low levels of serum selenium, selenoprotein P (SELENOP), and the selenocysteine-containi...
Article
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Introduction Growing evidence suggests a causal role for atherosclerotic vascular disease in cognitive impairment and dementia. Atherosclerosis may present as monovascular disease (monoVD) or as widespread polyvascular atherosclerotic disease (polyVD). Evidence on the relationship between monoVD or polyVD and cognitive impairment is limited. Metho...
Article
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Despite intensive preventive cardiovascular disease (CVD) efforts, substantial residual CVD risk remains even for individuals receiving all guideline-recommended interventions. Niacin is an essential micronutrient fortified in food staples, but its role in CVD is not well understood. In this study, untargeted metabolomics analysis of fasting plasma...
Preprint
The immune system plays a crucial role in many human diseases. In this context, genome-wide association studies (GWAS) offer valuable insights to elucidate the role of immunity in health and disease. The present multi-omics study aimed to identify genetic determinants of immune cell type distributions in the blood of healthy individuals and to asse...
Article
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Research across a number of different areas in psychology has long shown that optimism and pessimism are predictive of a number of important future life outcomes. Despite a vast literature on the correlates and consequences, we know very little about how optimism and pessimism change across adulthood and old age and the sociodemographic factors tha...
Article
OBJECTIVE Determining the cause of severe insulin resistance and early-onset diabetes in the case of a young woman in which a wide range of differential diagnoses did not apply. RESEARCH DESIGN AND METHODS Diagnostic workup including medical history, physical examination, specialist consultations, imaging methods, laboratory assessment, and geneti...
Preprint
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DNA methylation (DNAm) is an epigenetic mark with essential roles in disease development and predisposition. Here, we created genome-wide maps of methylation quantitative trait loci (meQTL) in three peripheral tissues and used Mendelian randomization (MR) analyses to assess the potential causal relationships between DNAm and risk for two common neu...
Article
Background Phenylacetylglutamine (PAGln) is a phenylalanine‐derived metabolite produced by gut microbiota with mechanistic links to hear failure (HF)‐relevant phenotypes. We sought to investigate the prognostic value of PAGln in patients with stable HF. Methods and results Fasting plasma PAGln levels were measured by stable‐isotope‐dilution LC‐MS/...
Preprint
Full-text available
Introduction: Growing evidence suggests a causal role for atherosclerotic vascular disease in cognitive impairment and dementia. Atherosclerosis may present as monovascular disease (monoVD) or as widespread polyvascular atherosclerotic disease polyVD). Evidence on the relationship between monoVD or polyVD and cognitive impairment is limited. Method...
Article
The baroreflex is a powerful physiological mechanism for rapidly adjusting heart rate in response to changes in blood pressure. Spontaneous baroreflex sensitivity (BRS) has been shown to decrease with age. However, studies of sex differences in these age-related changes are rare. Here we investigated several markers of spontaneous baroreflex functi...
Preprint
Full-text available
Aging is a complex process influenced by mechanisms operating at numerous levels of functioning. Multiple biomarkers of age have been identified, yet we know little about how the different alternative age indicators are intertwined. In the Berlin Aging Study II, we examined how levels and seven-year changes in indicators derived from blood assays,...
Article
Full-text available
Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-sha...
Preprint
Full-text available
Background: Change in body weight during the COVID-19 pandemic as an unintended side effect of lockdown measures has been predominantly reported for younger and middle-aged adults. However, information on older adults for which weight loss is known to result in adverse outcomes, is scarce. Aims: Describe body weight change in older adults before, d...
Article
Full-text available
High serum thyroid-stimulating hormone (TSH) levels have previously been associated with a low estimated glomerular filtration rate (eGFR), but studies associating thyroid hormone levels with albuminuria revealed inconsistent results. We used cross-sectional data from 7933 individuals aged 20 to 93 years of the Berlin Aging Study II and the Study o...
Article
Background: Selenium is essential for expression and proper function of a set of redox active selenoproteins implicated in aging-relevant diseases, e.g. type 2 diabetes mellitus (T2D) and hypertension. However, data in cohorts of older adults, particularly with respect to different Se biomarkers and sex-specific analyses are sparse. Objective: T...
Article
Many sleep less than recommended without experiencing daytime sleepiness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less slee...
Article
Full-text available
Abstract Physical activity (PA) has a substantial impact on health and mortality. Besides questionnaires that rely on subjective assessment of activity levels, accelerometers can help to objectify an individual’s PA. In this study, variables estimating PA and sleep time obtained through the wGT3X-BT activity monitor (ActiGraph LLC, USA) in 797 part...
Article
Aims: Precision microbiome modulation as a novel treatment strategy is a rapidly evolving and sought goal. The aim of this study is to determine relationships among systemic gut microbial metabolite levels and incident cardiovascular disease risks to identify gut microbial pathways as possible targets for personalized therapeutic interventions. M...
Article
Aim: Aim of the current study was to describe the prevalence, incidence, and severity of T2D in a cohort of older men and women aged 60 years and above over the course of on average seven years, since longitudinal data on this topic are scarce for this age group in Germany. Methods: Baseline data of 1,671 participants of the Berlin Aging Study I...
Article
Full-text available
Artificial sweeteners are widely used sugar substitutes, but little is known about their long-term effects on cardiometabolic disease risks. Here we examined the commonly used sugar substitute erythritol and atherothrombotic disease risk. In initial untargeted metabolomics studies in patients undergoing cardiac risk assessment (n = 1,157; discovery...
Article
Full-text available
Background Patients with Type 2 diabetes mellitus (T2D) are at risk for micro- and macrovascular complications. Implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The epigenetic clock estimates an individual’s biological age using DNA methylation profiles. Methods In...
Article
Full-text available
Introduction People age biologically at different rates. Epigenetic clock-derived DNA methylation age acceleration (DNAmAA) is among the most promising markers proposed to assess the interindividual differences in biological age. Further research is needed to evaluate the characteristics of the different epigenetic clock biomarkers available with r...
Preprint
Full-text available
Background: Lipoprotein(a) [Lp(a)] has recently been gaining increasing interest, with numerous studies pointing to a causal relationship with cardiovascular disease, coronary heart disease, as well as aortic valve stenosis. However, so far only a few studies have assessed the association between Lp(a) and pulmonary health and there have been some...
Article
Full-text available
Objectives: Throughout 2021, the COVID-19 pandemic caused renewed restrictions across Germany. Given the growing evidence that the pandemic negatively affects older adults' health and well-being, this study investigated health sensitivity (emotional reactions to momentary health challenges age, morbidity, perceived COVID-19 risks and worries) amon...
Preprint
Full-text available
Many sleep less than recommended without experiencing daytime tiredness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep...
Article
Full-text available
Domains of social privilege are predictive of a number of key aging outcomes, such as physical and cognitive functioning. However, less is known about the dynamic interplay of - related but distinct- domains of privilege and how they are associated with cognitive and physical functioning. In the following project, we aim to close this gap by examin...
Article
Full-text available
Background Although an inverse association between type II diabetes mellitus and Lipoprotein (a) [LP(a)] has already been well researched, there is sparse data on the association between metabolic syndrome (MetS) with Lp(a). MetS is highly prevalent in older people and insulin resistance in MetS might link Lp(a) with MetS. Thus, we analyzed the ass...
Article
Full-text available
Particularly older people are at risk for deficient vitamin D levels, as their capability for cutaneous synthetization is lower and they are often less exposed to sunlight. However, the resulting impact on one individual’s health is not fully understood. To examine potential consequences of low vitamin D levels for health of older people, we examin...
Article
Full-text available
Metabolic syndrome (MetS) refers to risk factors for cardiovascular disease associated with reduced physical fitness, higher disease burden, and impaired cognitive functions. Available evidence indicates that metabolic functioning is related to brain structure at the level of specific indicators, such as hypertension and voxel-based morphometry, re...
Article
Full-text available
High-quality biomarkers are needed to predict age-related phenotypes and evaluate health-related interventions. Telomere length has been known as a biomarker of aging for some time, however, its potential for clinical use is limited. Epigenetic age estimators and biological age (bioage) composites have been developed and refined over the past decad...
Article
Full-text available
Age-related elevations in inflammation are associated with both neurodegeneration and increased frailty in older adults. Here we used state-of-the-art diffusion-MRI (dMRI) methods to examine how specific markers of white matter (WM), including fiber density [FD], fiber cross-section [FC], and extracellular cerebral spinal fluid [CSF] are linked to...
Conference Paper
Full-text available
The diagnosis of metabolic syndrome (MetS) relies on cut-off values for five cardiovascular risk factors, three of which must be met to make the diagnosis. While this approach has certain advantages in the clinical setting, it only allows a binary classification relying on cut-off values. Thus, individuals receiving the same MetS diagnosis may diff...
Article
Full-text available
Background: The gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular disease pathogenesis in animal models via modulation of adrenergic receptor signaling. Methods: Here we examined both clinical and mechanistic relationship...
Article
Full-text available
Genetic variants in UMOD associate with kidney function and hypertension. These phenotypes are also linked to sex-related differences and impairment in cognitive and physical function in older age. Here we evaluate longitudinal associations between a common UMOD rs4293393-A>G variant and changes in estimated glomerular filtration rate (eGFR), blood...
Preprint
Physical activity has a substantial impact on health and mortality. Besides questionnaires that rely on subjective assessment of activity levels, accelerometers can help to objectify an individual's physical activity. Physical activity was assessed with the GT3X activity monitor (ActiGraph LLC, USA) in 797 participants of the Berlin Aging Study II...
Article
Full-text available
The decline in episodic memory (EM) performance is a hallmark of cognitive aging and an early clinical sign in Alzheimer’s disease (AD). In this study, we conducted an epigenome-wide association study (EWAS) using DNA methylation (DNAm) profiles from buccal and blood samples for cross-sectional (n = 1019) and longitudinal changes in EM performance...
Article
Full-text available
Background Although potent lipid-lowering therapies are available, patients commonly fall short of recommended low-density lipoprotein cholesterol (LDL-C) levels. The aim of this study was to examine the relationship between familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] and LDL-C goal attainment, as well as the prevalence a...
Article
Full-text available
Epigenome-wide association studies (EWAS) assessing the link between DNA methylation (DNAm) and phenotypes related to structural brain measures, cognitive function, and neurodegenerative diseases are becoming increasingly more popular. Due to the inaccessibility of brain tissue in humans, several studies use peripheral tissues such as blood, buccal...
Article
Full-text available
Adverse effects of psychological stress on physical and mental health, especially in older age, are well documented. How perceived stress relates to the epigenetic clock measure, DNA methylation age acceleration (DNAmAA), is less well understood and existing studies reported inconsistent results. DNAmAA was estimated from five epigenetic clocks (7-...
Article
Full-text available
Biomarkers defining biological age are typically laborious or expensive to assess. Instead, in the current study, we identified parameters based on standard laboratory blood tests across metabolic, cardiovascular, inflammatory, and kidney functioning that had been assessed in the Berlin Aging Study (BASE) (n = 384) and Berlin Aging Study II (BASE-I...
Article
Full-text available
History-graded increases in older adults’ levels of cognitive performance are well documented, but little is known about historical shifts in within-person change: cognitive decline and onset of decline. We combined harmonized perceptual-motor speed data from independent samples recruited in 1990 and 2010 to age-match 2,008 longitudinal observation...
Article
Full-text available
Telomeres are repetitive nucleotide sequences at the ends of each chromosome. It has been hypothesized that telomere attrition evolved as a tumor suppressor mechanism in large long-lived species. Long telomeres can silence genes millions of bases away through a looping mechanism called telomere position effect over long distances (TPE-OLD). The fun...
Article
Full-text available
From a biological perspective, humans differ in the speed they age, and this may manifest in both mental and physical health disparities. The discrepancy between an individual’s biological and chronological age of the brain (“brain age gap”) can be assessed by applying machine learning techniques to Magnetic Resonance Imaging (MRI) data. Here, we e...
Preprint
Patients with diabetes mellitus are at risk for micro- and macrovascular complications that are responsible for a substantial part of the individual health burden and socio-economic costs. Therefore, implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The “epigenetic c...
Article
Full-text available
Adverse effects of low vitamin D level on mortality and morbidity are controversially discussed. Especially older people are at risk for vitamin D deficiency and therefore exposed to its potentially harmful consequences. A way of measuring differences in the biological age is through DNA methylation age (DNAm age) and its deviation from chronologic...
Article
Introduction: There is evidence of an association between markers of cardiac injury and cognition in patients with cardiovascular disease. We hypothesized that levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with cognitive performance and cognitive decline in a population of predominantly healthy older adults. Methods: We...
Article
Full-text available
Background: We assess the impact of prevention strategies regarding type 2 diabetes as a modifiable risk factor for dementia and its consequences for the future number of dementia patients in Germany. Methods: We used a random sample of health claims data (N = 250,000) of insured persons aged 50+ drawn in 2014, and data on population size and death...
Poster
Yearly dietary Tyrosine intake in relationship with Locus Coeruleus volume and neuropsychological measures Abstract: It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia [1,2,3,4,5,6]. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergi...
Article
Background: An inverse association between lipoprotein(a) (Lp[a]) and type 2 diabetes mellitus is well documented. However, data on the association of the metabolic syndrome (MetS) with Lp(a) are sparse. Methods: Cross-sectional data for MetS and Lp(a) were available for 5743 BASE-II and SHIP-0 participants (48.7% men; age 58 [20-85]|years) (BAS...