Publications by authors named "Slagboom P"

Objective: Plant-based diets (PBD) are generally promoted as beneficial for health. However, whether this is also the case at older ages, when energy deficits, muscle loss and frailty affect health, is unclear. Research has shown that among older adults, particularly in men, a healthful PBD is associated with a lower frailty risk.

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  • Metabolomics using HILIC-MS is effective for identifying polar metabolites and aiding in biomarker discovery, but matrix effects can complicate biological analysis.
  • Evaluation of matrix effects is critical in method development, and this study tested two techniques: stable isotope labeled-internal standards and post-column infusion (PCI).
  • Results indicated that the PCI method is more advantageous for untargeted analysis, showing better performance in assessing matrix effects and highlighting significant ion suppression in various plasma samples.
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Introduction: Depending on age, sex, and familial longevity, alterations in thyroid status occur frequently, and often co-occur with differences in other hormonal axes. However, studies that explore the effects of thyroid status modulation on other hormonal axes remain scarce. We aim to determine the effects of thyroid status modulation on prolactin, IGF-1, cortisol, LH, testosterone, and SHBG levels.

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Across the lifespan, diet and physical activity profiles substantially influence immunometabolic health. DNA methylation, as a tissue-specific marker sensitive to behavioral change, may mediate these effects through modulation of transcription factor binding and subsequent gene expression. Despite this, few human studies have profiled DNA methylation and gene expression simultaneously in multiple tissues or examined how molecular levels react and interact in response to lifestyle changes.

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Background: Metabolomic scores based on age (MetaboAge) and mortality (MetaboHealth) are considered indicators of overall health, but their association with cognition in the general population is unknown. Therefore, the association between MetaboAge/MetaboHealth and level and decline in cognition was studied, as were differences between men and women.

Methods: Data of 2821 participants (50% women, age range 45-75) from the Doetinchem Cohort Study was used.

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Oxylipins are well-known lipid mediators in various inflammatory conditions. Their endogenous concentrations range from low picomolar to nanomolar, and there are growing demands to determine their concentrations in low-volume matrices for pathological studies, including blood, cerebrospinal fluids from animal disease models, infants, and microsampling devices. Most of the published quantification methods for comprehensive profiling of oxylipins still require more than 50 µL plasma as a starting volume to detect these low levels.

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Background: Exercise and nutrition interventions can slow ageing-induced decline in physiology. However, effects are heterogeneous and usually studied separately per outcome domain. In the VOILA study, we simultaneously study various health outcomes relevant for older adults and the inter-individual heterogeneity in response to a lifestyle intervention.

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Background: Obesity may affect an individual's immune response and subsequent risk of infection, such as a SARS-CoV-2 infection. It is less clear whether overweight and long-term obesity also constitute risk factors. We investigated the association between the degree and duration of overweight and obesity and SARS-CoV-2 infection.

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  • The study focused on the relationship between Torquetenovirus (TTV) levels, inflammation markers, and the risk of Ischemic Heart Disease (IHD) in older adults, revealing limited research on this topic.
  • Findings from 900 non-IHD participants and 86 IHD individuals indicated that elevated TTV viremia was a significant predictor of IHD risk, particularly in males and in conjunction with other health factors like diabetes and smoking.
  • The research suggests that high TTV levels are linked to increased inflammation and may contribute to IHD risk through mechanisms related to aging and immune response deterioration.
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The 1-HMR metabolomics-based MetaboHealth score, comprised of 14 serum metabolic markers, associates with disease-specific mortality, but it is unclear whether the score also reflects cognitive changes and functional impairment. We aimed to assess the associations between the MetaboHealth score with cognitive function and functional decline in older adults at increased cardiovascular risk. A total of 5292 older adults free of dementia at baseline with mean age 75.

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  • This study examined the link between plasma biomarkers indicating endothelial dysfunction and cognitive performance in a sample of 9,414 older adults from the Netherlands, aged 57 to 93 years.
  • Researchers created a composite score from three specific biomarkers and assessed various cognitive functions like executive function and memory.
  • Results indicated a small, consistent association between higher endothelial dysfunction scores and poorer cognitive performance, but no evidence suggested that these markers influenced cognitive decline over time.
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  • The study evaluates the Glasgow Prognostic Score (GPS), which combines albumin and C-reactive protein levels, as a tool for assessing health issues and mortality in older cancer patients.
  • It finds that older patients with abnormal GPS are more likely to be frail and have higher one-year mortality rates compared to those with normal GPS.
  • The GPS also enhances the predictive accuracy for mortality risk when combined with other clinical factors, indicating its potential usefulness in cancer treatment decisions for older adults.
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Existing metabolomic clocks exhibit deficiencies in capturing the heterogeneous aging rates among individuals with the same chronological age. Yet, the modifiable and non-modifiable factors in metabolomic aging have not been systematically studied. Here, a new aging measure-MetaboAgeMort-is developed using metabolomic profiles from 239,291 UK Biobank participants for 10-year all-cause mortality prediction.

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  • Biomarkers of aging (BOA) are special measurements that can help scientists understand how old someone is on a biological level and how this changes with treatments.
  • Recently, many new BOA have been discovered that could really help people live healthier lives as they age, but there are some problems getting these ideas into actual medical practice.
  • Experts found six main challenges that are stopping BOA from being used more widely and suggested ways to make them better, such as ensuring they are easy to access and useful for everyone.
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  • - The study investigates the role of oxidized LDL particles (LDLox) in assessing cardiometabolic risk, focusing on their relationship with other biomarkers and risk factors using data from 1089 participants aged 40-75.
  • - Researchers performed correlation analyses and developed machine learning models to predict risks associated with high blood pressure and obesity, achieving promising validation scores that highlighted the significance of LDLox.
  • - The findings provide new insights into how LDL oxidation may interact with aging markers to influence cardiometabolic health, suggesting that further research with larger groups could enhance clinical assessment tools.
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Background: H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals.

Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors.

Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays.

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Molecular effects of lifestyle interventions are typically studied in a single tissue. Here, we perform a secondary analysis on the sex-specific effects of the Growing Old TOgether trial (GOTO, trial registration number GOT NL3301 ( https://onderzoekmetmensen.nl/nl/trial/27183 ), NL-OMON27183 , primary outcomes have been previously reported in ref.

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Recent studies have shown that elevated concentrations of unconjugated bilirubin (UCB) may be a protective host factor against the development of noncommunicable diseases (NCDs), whereas low levels of UCB are associated with the opposite effect. The results of this European study, in which 2,489 samples were tested for their UCB concentration using high-performance liquid chromatography (HPLC) and additional data from the MARK-AGE database were used for analysis, provide further evidence that elevated UCB concentrations are linked to a lower risk of developing NCDs and may act as a predictive marker of biological aging as individuals with elevated UCB concentrations showed favorable outcomes in metabolic health and oxidative-stress-related biomarkers. These findings underline the significance of studying individuals with moderate hyperbilirubinemia and investigate UCB routinely, also in the setting of aging, since this condition affects millions of people worldwide but has been underrepresented in clinical research and practice until now.

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Research Question: Are age at last childbirth and number of children, as facets of female reproductive health, related to individual lifespan or familial longevity?

Design: This observational study included 10,255 female participants from a multigenerational historical cohort, the LINKing System for historical family reconstruction (LINKS), and 1258 female participants from 651 long-lived families in the Leiden Longevity Study (LLS). Age at last childbirth and number of children, as outcomes of reproductive success, were compared with individual and familial longevity using the LINKS dataset. In addition, the genetic predisposition in the form of a polygenic risk score (PRS) for age at menopause was studied in relation to familial longevity using the LLS dataset.

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Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors.

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Trimethylamine -oxide (TMAO) is a circulating microbiome-derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO-to-precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in-depth analysis of their genetic, gut microbial, and dietary determinants.

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Background: Aging triggers intricate physiological changes, particularly in whole-body fat-free mass (FFM) and handgrip strength, affecting overall health and independence. Despite existing research, the broader significance of how muscle health is affected by the intricate interplay of lifestyle factors simultaneously during aging needs more exploration. This study aims to examine how nutrition, physical activity, and sleep impact on FFM and handgrip strength in middle-aged men and women, facilitating future personalized recommendations for preserving muscle health.

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Plant-based diets (PBD) may offer various health benefits and contribute to a sustainable way of life, but, if not planned correctly, may also confer risks, e.g., by focusing on plant foods with low nutrient density, such as foods primarily consisting of refined carbohydrates.

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Background: The gut-derived metabolite Trimethylamine N-oxide (TMAO) and its precursors - betaine, carnitine, choline, and deoxycarnitine - have been associated with an increased risk of cardiovascular disease, but their relation to cognition, neuroimaging markers, and dementia remains uncertain.

Methods: In the population-based Rotterdam Study, we used multivariable regression models to study the associations between plasma TMAO, its precursors, and cognition in 3,143 participants. Subsequently, we examined their link to structural brain MRI markers in 2,047 participants, with a partial validation in the Leiden Longevity Study (n = 318).

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Background: There is divergence in the rate at which people age. The concept of biological age is postulated to capture this variability, and hence to better represent an individual's true global physiological state than chronological age. Biological age predictors are often generated based on cross-sectional data, using biochemical or molecular markers as predictor variables.

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