Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of... Show moreHealthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the patient. It is therefore essential to take aging into consideration when investigating immune cells and their responses in atherosclerosis studies. This thesis describes research exploring the impact of aging on the immunological landscape in atherosclerotic cardiovascular disease using single-cell profiling. Through the use of a highly translational aging mouse model of atherosclerosis, we characterized inflammation in the plaques of young versus old mice. We discovered new cell types (T and B cells) not present in young mice with atherosclerosis. These cells secrete a variety of inflammatory factors that may contribute to the disease process and exacerbate arteriosclerosis. While the aged B cell is more prevalent in female mice, the aged T cell is more abundant in male mice. We then also found these aged cells in the blood and plaques of cardiovascular disease patients. These aged cell types could be interesting targets for future treatments against progression of atherosclerotic cardiovascular disease. Show less
Smit, V.; Mol, J. de; Bernabé Kleijn, M.N.A.B.; Depuydt, M.A.C.; Winther, M.P.J. de, Bot, I.; Kuiper, J.; Foks, A.C. 2024
Atherosclerosis, the main underlying pathology of cardiovascular disease, is a chronic inflammatory disease characterized by lipid accumulation and immune cell responses in the vascular wall,... Show moreAtherosclerosis, the main underlying pathology of cardiovascular disease, is a chronic inflammatory disease characterized by lipid accumulation and immune cell responses in the vascular wall, resulting in plaque formation. It is well-known that atherosclerosis prevalence and manifestation vary by sex. However, sexual dimorphism in the immune landscape of atherosclerotic plaques has up to date not been studied at high-resolution. In this study, we investigated sex-specific differences in atherosclerosis development and the immunological landscape of aortas at single-cell level in aged Ldlr-/- mice.We compared plaque morphology between aged male and female chow diet-fed Ldlr-/- mice (22 months old) with histological analysis. Using single-cell RNA-sequencing and flow cytometry on CD45+ immune cells from aortas of aged Ldlr-/- mice, we explored the immune landscape in the atherosclerotic environment in males and females.We show that plaque volume is comparable in aged male and female mice, and that plaques in aged female mice contain more collagen and cholesterol crystals, but less necrotic core and macrophage content compared to males. We reveal increased immune cell infiltration in female aortas and found that expression of pro-atherogenic markers and inflammatory signaling pathways was enriched in plaque immune cells of female mice. Particularly, female aortas show enhanced activation of B cells (Egr1, Cd83, Cd180), including age-associated B cells, in addition to an increased M1/M2 macrophage ratio, where Il1b+ M1-like macrophages display a more pro-inflammatory phenotype (Nlrp3, Cxcl2, Mmp9) compared to males. In contrast, increased numbers of age-associated Gzmk+CD8+ T cells, dendritic cells, and Trem2+ macrophages were observed in male aortas.Altogether, our findings highlight that sex is a variable that contributes to immunological differences in the atherosclerotic plaque environment in mice and provide valuable insights for further preclinical studies into the impact of sex on the pathophysiology of atherosclerosis. Show less
Sluiskes, M.; Goeman, J.; Beekman, M.; Slagboom, E.; Akker, E. van den; Putter, H.; Rodríguez-Girondo, M. 2024
Aging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While... Show moreAging is a multifaceted and intricate physiological process characterized by a gradual decline in functional capacity, leading to increased susceptibility to diseases and mortality. While chronological age serves as a strong risk factor for age-related health conditions, considerable heterogeneity exists in the aging trajectories of individuals, suggesting that biological age may provide a more nuanced understanding of the aging process. However, the concept of biological age lacks a clear operationalization, leading to the development of various biological age predictors without a solid statistical foundation. This paper addresses these limitations by proposing a comprehensive operationalization of biological age, introducing the “AccelerAge” framework for predicting biological age, and introducing previously underutilized evaluation measures for assessing the performance of biological age predictors. The AccelerAge framework, based on Accelerated Failure Time (AFT) models, directly models the effect of candidate predictors of aging on an individual’s survival time, aligning with the prevalent metaphor of aging as a clock. We compare predictors based on the AccelerAge framework to a predictor based on the GrimAge predictor, which is considered one of the best-performing biological age predictors, using simulated data as well as data from the UK Biobank and the Leiden Longevity Study. Our approach seeks to establish a robust statistical foundation for biological age clocks, enabling a more accurate and interpretable assessment of an individual’s aging status. Show less
Sluiskes, M.H.; Goeman, J.J.; Beekman, M.; Slagboom, P.E.; Putter, H.; Rodriguez-Girondo, M. 2024
Background There is divergence in the rate at which people age. The concept of biological age is postulated to cap‑ ture this variability, and hence to better represent an individual’s true global... Show moreBackground There is divergence in the rate at which people age. The concept of biological age is postulated to cap‑ ture 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. It is assumed that the diference between chronological and predicted biological age is informative of one’s chronological age-independent aging divergence ∆. Methods We investigated the statistical assumptions underlying the most popular cross-sectional biological age pre‑ dictors, based on multiple linear regression, the Klemera-Doubal method or principal component analysis. We used synthetic and real data to illustrate the consequences if this assumption does not hold. Results The most popular cross-sectional biological age predictors all use the same strong underlying assumption, namely that a candidate marker of aging’s association with chronological age is directly informative of its association with the aging rate ∆. We called this the identical-association assumption and proved that it is untestable in a crosssectional setting. If this assumption does not hold, weights assigned to candidate markers of aging are uninformative, and no more signal may be captured than if markers would have been assigned weights at random. Conclusions Cross-sectional methods for predicting biological age commonly use the untestable identical-associa‑ tion assumption, which previous literature in the feld had never explicitly acknowledged. These methods have inher‑ ent limitations and may provide uninformative results, highlighting the importance of researchers exercising caution in the development and interpretation of cross-sectional biological age predictors Show less
Kochlik, B.; Herpich, C.; Moreno-Villanueva, M.; Klaus, S.; Müller-Werdan, U.; Weinberger, B.; ... ; Norman, K. 2023
Growth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with... Show moreGrowth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with combined cognitive-frailty-and-depression in older (i.e. ≥ 55 years) and younger adults of the MARK-AGE study. In the present work, samples and data of MARK-AGE (“European study to establish bioMARKers of human AGEing“) participants (N = 2736) were analyzed. Cognitive frailty was determined by the global cognitive functioning score (GCF) and depression by the Self-Rating Depression Scale (SDS score). Adults were classified into three groups: (I) neither-cognitive-frailty-nor-depression, (II) either-cognitive-frailty-or-depression or (III) both-cognitive-frailty-and-depression. Cross-sectional associations were determined by unadjusted and by age, BMI, sex, comorbidities and hsCRP-adjusted linear and logistic regression analyses. Cognitive frailty, depression, age and GDF15 were significantly related within the whole study sample. High GDF15 levels were significantly associated with both-cognitive-frailty-and-depression (adjusted β = 0.177 [0.044 – 0.310], p = 0.009), and with low GCF scores and high SDS scores. High GDF15 concentrations and quartiles were significantly associated with higher odds to have both-cognitive-frailty-and-depression (adjusted odds ratio = 2.353 [1.267 – 4.372], p = 0.007; and adjusted odds ratio = 1.414 [1.025 – 1.951], p = 0.035, respectively) independent of age, BMI, sex, comorbidities and hsCRP. These associations remained significant when evaluating older adults. We conclude that plasma GDF15 concentrations are significantly associated with combined cognitive-frailty-and-depression status and, with cognitive frailty and depressive symptoms separately in old as well as young community-dwelling adults. Show less
Background: Infrared thermography is a growing area of interest in sports science due to the potential of skin temperature (T-sk) measurements to provide valuable information from rest to exercise.... Show moreBackground: Infrared thermography is a growing area of interest in sports science due to the potential of skin temperature (T-sk) measurements to provide valuable information from rest to exercise. However, limited research exists on T-sk in older adults and the impact of factors such as sex and cardiorespiratory fitness (CRF) on T-sk. This study aims to investigate T-sk at rest and after acute exercise in older adults and assess whether sex or CRF influences T-sk.Methods: Ninety-two participants (41 women, 68.48 +/- 3.01 years) were examined with a thermographic camera in a conditioned room (23.02 +/- 3.01 degrees C) at rest and after a graded protocol. The T-sk of 25 regions of interest (ROIs) were extracted and analysed.Results: Men had higher overall T-sk at rest in 76% of ROIs, showing significant differences (p < 0.010) in six specific ROIs, independent of CRF. Both sexes had similar T-sk responses after graded exercise, with increases in distal parts (1.06 +/- 0.50 C-degrees), decreases in proximal parts (-0.62 +/- 0.42 degrees C), and stable central T-sk (0.23 +/- 0.59 degrees C). Increases in lower limb T-sk were significantly associated with CRF in men and women (beta = 0.438, p = 0.001, and beta = 0.535, p < 0.001, respectively), explaining 17% and 27% of the variance, respectively.Conclusions: This study demonstrates a sex-specific effect on resting T-sk in older adults, suggesting that sex-specific T-sk patterns should be considered when analysing T-sk in this population. Additionally, the association between increases in lower limb T-sk and CRF suggests that T-sk could be a promising predictor of CRF in older adults. Show less
BackgroundLoss of epigenetic control is a hallmark of aging. Among the most prominent roles of epigenetic mechanisms is the inactivation of one of two copies of the X chromosome in females through... Show moreBackgroundLoss of epigenetic control is a hallmark of aging. Among the most prominent roles of epigenetic mechanisms is the inactivation of one of two copies of the X chromosome in females through DNA methylation. Hence, age-related disruption of X-chromosome inactivation (XCI) may contribute to the aging process in women.MethodsWe analyzed 9,777 CpGs on the X chromosome in whole blood samples from 2343 females and 1688 males (Illumina 450k methylation array) and replicated findings in duplicate using one whole blood and one purified monocyte data set (in total, 991/924 females/males). We used double generalized linear models to detect age-related differentially methylated CpGs (aDMCs), whose mean methylation level differs with age, and age-related variably methylated CpGs (aVMCs), whose methylation level becomes more variable with age.ResultsIn females, aDMCs were relatively uncommon (n = 33) and preferentially occurred in regions known to escape XCI. In contrast, many CpGs (n = 987) were found to display an increased variance with age (aVMCs). Of note, the replication rate of aVMCs was also high in purified monocytes (94%), indicating an independence of cell composition. aVMCs accumulated in CpG islands and regions subject to XCI suggesting that they stemmed from the inactive X. In males, carrying an active copy of the X chromosome only, aDMCs (n = 316) were primarily driven by cell composition, while aVMCs replicated well (95%) but were infrequent (n = 37).ConclusionsOur results imply that age-related DNA methylation differences at the inactive X chromosome are dominated by the accumulation of variability. Show less
Roos, R.; Pepping, R.M.C.; Aken, M.O. van; Labots, G.; Lahdidioui, A.; Berg, J.M.W. van den; ... ; Nieuwkoop, C. van 2023
Introduction Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as... Show moreIntroduction Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway (‘The Hague RTI Care Bridge’) developed with the aim to treat and coordinate care for these patients outside the hospital.Methods and analysis This is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life.Ethics and dissemination The Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals. Show less
The general aim of this thesis was to study the frequency, causes and consequences of pathologic brain aging specifically focusing on sub-clinical and clinical MRI manifestations of vascular (small... Show moreThe general aim of this thesis was to study the frequency, causes and consequences of pathologic brain aging specifically focusing on sub-clinical and clinical MRI manifestations of vascular (small vessel disease) and neurodegenerative (brain atrophy) disease. A second aim was to improve the accuracy of the tools to quantify brain tissue so to better reflect the imaging characteristics of older people. All data presented in this thesis are from the AGES-Reykjavik Study including 5764 elderly men and women. The data is based on cross-sectional and longitudinal assessments of the brain with MRI measures. Show less
Worldwide, life expectancy has increased, which also resulted in an increasing number of people reaching old age. With aging, several age-related diseases commonly occur, such as dementia,... Show moreWorldwide, life expectancy has increased, which also resulted in an increasing number of people reaching old age. With aging, several age-related diseases commonly occur, such as dementia, osteoporosis and cardiovascular disease. The occurence of these diseases with age is highly heterogeneous. The research described in this thesis assessed the role of thyroid hormones in the etiology of age-related diseases. Based on the results, variation in blood levels of thyroid hormones do not appear to play a major role in the development of cogniitve decline, osteoporosis, anemia, diabetes mellitus or cardiovascular disease. Therefore, we conclude that is unlikely that thyroid hormones are a modifiable risk factor in the aging process. Nevertheless, many other research questions remain regarding thyroid hormones and older individuals. Show less
Zwartbol, M.H.T.; Ghaznawi, R.; Jaarsma-Coes, M.; Kuijf, H.; Hendrikse, J.; Bresser, J. de; ... ; UCC-SMART Study Grp 2022
White matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function.In... Show moreWhite matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function.In 563 patients with vascular disease (58 +/- 10 years), we examined the relationship between WMH volume, shape, and cognitive functioning. WMH volume and shape were automatically determined on 1.5T brain MRI data. Standardized linear regression analyses estimated the association between WMH volume and shape (concavity index, solidity, convexity, fractal dimension, and eccentricity) and memory and executive functioning, adjusted for age, sex, educational level, and reading ability.Larger WMH volumes were associated with lower executive functioning Z-scores ( b (95%-CI):-0.09 (-0.17;-0.01)). Increased shape complexity of periventricular/confluent WMH associated with lower exec-utive functioning (concavity index + 1SD:-0.13 (-0.20;-0.06); solidity-1SD:-0.09 (-0.17;-0.02)) and lower memory function (fractal dimension + 1SD:-0.10 (-0.18;-0.02)). Of note, the association between concav-ity index and executive functioning was independent of WMH volume (-0.12 (-0.19;-0.04)). Our results suggest that WMH shape contains additional information about WMH burden, not other-wise captured by WMH volume.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Giacconi, R.; D'Aquila, P.; Malavolta, M.; Piacenza, F.; Burkle, A.; Villanueva, M.M.; ... ; Provinciali, M. 2022
Aging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be... Show moreAging and age-related diseases have been linked to microbial dysbiosis with changes in blood bacterial DNA concentration. This condition may promote chronic low-grade inflammation, which can be further aggravated by antioxidant nutrient deficiency. Low plasma carotenoids are associated with an increased risk of inflammation and cellular damage and predict mortality. However, no evidence is yet available on the relationship between antioxidants and the blood bacterial DNA (BB-DNA). Therefore, this study aimed to compare BB-DNA from (a) GO (nonagenarian offspring), (b) age-matched controls (Randomly recruited Age-Stratified Individuals from the General population [RASIG]), and (c) spouses of GO (SGO) recruited in the MARK-AGE project, as well as to investigate the association between BB-DNA, behavior habits, Charlson Comorbidity Index (CCI), leucocyte subsets, and the circulating levels of some antioxidants and oxidative stress markers. BB-DNA was higher in RASIG than GO and SGO, whereas GO and SGO participants showed similar values. BB-DNA increased in smokers and males with CCI >= 2 compared with those with CCI <= 1 within RASIG. Moreover, BB-DNA was positively associated with lymphocyte, neutrophil, and monocyte counts, but not with self-reported dietary habits. Higher quartiles of BB-DNA were associated with low lutein and zeaxanthin and elevated malondialdehyde plasma concentrations in RASIG. BB-DNA was also positively correlated with nitric oxide levels. Herein, we provide evidence of a reduced BB-DNA in individuals from long-living families and their spouses, suggesting a decreased microbial dysbiosis and bacterial systemic translocation. BB-DNA was also associated with smoking, CCI, leukocyte subsets, and some redox biomarkers in older participants. Show less
The experimental research in this thesis aims to gain more understanding of how the SCN network is organized and what is needed for network changes. More specifically, this work focused on the... Show moreThe experimental research in this thesis aims to gain more understanding of how the SCN network is organized and what is needed for network changes. More specifically, this work focused on the potential role of GABA and the GABAeric E/I balance in SCN network plasticity. Communication and synchronization in the SCN are important for the generation of a strong and coherent output signal. Under certain conditions, like long photoperiod, the phases of the individual SCN cells are more dispersed over the 24 hour cycle as evidenced by measurements of electrical activity and clock gene expression. Aging is also known to affect the network organization of the SCN with deterioration in synchronization among the individual SCN neurons. In this thesis, I present work that contributes to research questions regarding the effect of light exposure and/or aging on several characteristics of SCN network plasticity. Show less
The 14q32 locus is an imprinted region in the human genome which contains multiple non-coding RNAs. We investigated the role of the long non-coding RNA maternally expressed gene 8 (MEG8) in... Show moreThe 14q32 locus is an imprinted region in the human genome which contains multiple non-coding RNAs. We investigated the role of the long non-coding RNA maternally expressed gene 8 (MEG8) in endothelial function and its underlying mechanism. A 5-fold increase in MEG8 was observed with increased passage number in human umbilical vein endothelial cells (HUVECs), suggesting MEG8 is induced during aging. MEG8 knockdown resulted in a 1.8-fold increase in senescence, suggesting MEG8 might be protective during aging. The endothelial barrier was also impaired after MEG8 silencing. MEG8 knockdown resulted in reduced expression of microRNA (miRNA)-370 and -494 but not -127, -487b and -410. Overexpression of miRNA-370 or -494 partially rescued the MEG8-silencing-induced barrier loss. Mechanistically, MEG8 regulates expression of miRNA-370 and -494 at the mature miRNA level through interaction with the RNA-binding proteins cold-inducible RNA-binding protein (CIRBP) and hydroxyacyl-CoA dehydrogenase trifunctional multi-enzyme complex subunit beta (HADHB). Mature miRNA-370 and miRNA-494 were found to interact with CIRBP, whereas precursor miRNA-370 and miRNA-494 were found to interact with HADHB. Individual CIRBP and HADHB silencing resulted in downregulation of miRNA-370 and induction of miRNA-494. These results suggest MEG8 interacts with CIRBP and HADHB and contributes to miRNA processing at the post-transcriptional level. Show less
Wall, H.E.C. van der; Hassing, G.J.; Doll, R.J.; Westen, G.J.P. van; Cohen, A.F.; Selder, J.L.; ... ; Gal, P. 2022
ObjectiveThe aim of the present study was to develop a neural network to characterize the effect of aging on the ECG in healthy volunteers. Moreover, the impact of the various ECG features on aging... Show moreObjectiveThe aim of the present study was to develop a neural network to characterize the effect of aging on the ECG in healthy volunteers. Moreover, the impact of the various ECG features on aging was evaluated.Methods & resultsA total of 6228 healthy subjects without structural heart disease were included in this study. A neural network regression model was created to predict age of the subjects based on their ECG; 577 parameters derived from a 12‑lead ECG of each subject were used to develop and validate the neural network; A tenfold cross-validation was performed, using 118 subjects for validation each fold. Using SHapley Additive exPlanations values the impact of the individual features on the prediction of age was determined. Of 6228 subjects tested, 1808 (29%) were females and mean age was 34 years, range 18–75 years. Physiologic age was estimated as a continuous variable with an average error of 6.9 ± 5.6 years (R2 = 0.72 ± 0.04) . The correlation was slightly stronger for men (R2 = 0.74) than for women (R2 = 0.66). The most important features on the prediction of physiologic age were T wave morphology indices in leads V4 and V5, and P wave amplitude in leads AVR and II.ConclusionThe application of machine learning to the ECG using a neural network regression model, allows accurate estimation of physiologic cardiac age. This technique could be used to pick up subtle age-related cardiac changes, but also estimate the reversing of these age-associated effects by administered treatments. Show less
Hitzl, W.; Stamm, T.; Kloppenburg, M.; Ritter, M.; Gaisberger, M.; Zee-neuen, A. van der 2022
Background The present study aimed to predict the expected number of patients with osteoarthritis (OA) in Austria up to the year 2080. Methods Demographic data and population projections between... Show moreBackground The present study aimed to predict the expected number of patients with osteoarthritis (OA) in Austria up to the year 2080. Methods Demographic data and population projections between 2019 and 2080 were obtained from European authorities. Information about recent age- and sex-stratified prevalence of patients with self-reported physician-diagnosed OA was obtained from the Austrian Health Interview Survey (n = 15,771). Projections were stratified by age and sex; sensitivity analyses were performed based on aging, main (most likely), and growth scenarios of the population. Results Based on the projection, the overall increase in the total number of patients with OA from 2019 to 2080 will be 38% for men and women. In 2019, the highest number of OA-patients nested in the groups of persons aged 70-79 (n = 238,749) and 60-69 (n = 237,729) years. In 2080, the 80+ age group is predicted to have the highest number of OA with 421,548 individuals (i.e. factor 3.45 and factor 2.48 increase in the male and female group, respectively, compared to 2019), followed by the group aged 70-79 with 314,617 individuals (factor 1.45 and factor 1.28 increase in the male and female group, respectively, compared to 2019). Similar trends were found in the ageing and growing scenarios. Conclusions The projected increase in the occurrence of OA will likely lead to a substantial socioeconomic burden for the Austrian healthcare system in the near and far future. The current findings plead for the development of sustainable concepts for the treatment and prevention of OA by European authorities. Show less
The significance of classical risk factors in coronary artery disease (CAD) remains unclear in older age due to possible changes in underlying disease pathologies. Therefore, we conducted Mendelian... Show moreThe significance of classical risk factors in coronary artery disease (CAD) remains unclear in older age due to possible changes in underlying disease pathologies. Therefore, we conducted Mendelian Randomization approaches to investigate the causal relationship between classical risk factors and primary CAD in different age groups. A Mendelian Randomization study was conducted in European-ethnicity individuals from the UK Biobank population. Analyses were performed using data of 22,313 CAD cases (71.6% men) and 407,920 controls (44.5% men). Using logistic regression analyses, we investigated the associations between standardized genetic risk score and primary CAD stratified by age of diagnosis. In addition, feature importance and model accuracy were assessed in different age groups to evaluate predictive power of the genetic risk scores with increasing age. We found age-dependent associations for all classical CAD risk factors. Notably, body mass index (OR 1.22 diagnosis < 50 years; OR 1.02 diagnosis > 70 years), blood pressure (OR 1.12 < 50 years; OR 1.04 > 70 years), LDL cholesterol (OR 1.16 < 50 years; OR 1.02 > 70 years), and triglyceride levels (OR 1.11 < 50 years; 1.04 > 70 years). In line with the Mendelian Randomization analyses, model accuracy and feature importance of the classical risk factors decreased with increasing age of diagnosis. Causal determinants for primary CAD are age dependent with classical CAD risk factors attenuating in relation with primary CAD with increasing age. These results question the need for (some) currently applied cardiovascular disease risk reducing interventions at older age. Show less
Candel, B.G.J.; Ingen, I.B. van; Doormalen, I.P.H. van; Raven, W.; Mignot-Evers, L.A.A.; Jonge, E. de; Groot, B. de 2021
Purpose To assess how often baseline systolic blood pressure (SBP) could be retrieved from the Electronic Health Record (EHR) in older Emergency Department (ED) patients. Second, to assess whether... Show morePurpose To assess how often baseline systolic blood pressure (SBP) could be retrieved from the Electronic Health Record (EHR) in older Emergency Department (ED) patients. Second, to assess whether the difference between baseline SBP and initial SBP in the ED (Delta SBP) was associated with 30-day mortality. Methods A multicenter hypothesis-generating cohort study including patients >= 70 years. EHRs were searched for baseline SBPs. The association between Delta SBP and 30-day mortality was investigated. Results Baseline SBP was found in 220 out of 300 patients (73.3%; 95%CI 68.1-78.0%). In 72 patients with normal initial SBPs (133-166 mmHg) in the ED, fifteen (20.8%) had a negative Delta SBP with 20.0% mortality. A negative Delta SBP was associated with 30-day mortality (AHR 4.7; 1.7-12.7). Conclusion Baseline SBPs are often available in older ED patients. The Delta SBP has prognostic value and could be used as an extra variable to recognize hypotension in older ED patients. Future studies should clarify whether the Delta SBP improves risk stratification in the ED.Key summary pointsAim To investigate whether a baseline systolic blood pressure (SBP) in older Emergency Department (ED) patients of >= 70 years has prognostic value, when compared with the initial SBP at presentation in the ED (= Delta SBP). Findings A baseline SBP could be retrieved from the Electronic Health Record for most older ED patients (73.3%). A negative Delta SBP was associated with 30-day mortality. In 20% of the patients with a normal initial SBP in the ED, the Delta SBP was negative, with a high mortality rate. Message A baseline SBP value could be retrieved from the Electronic Health Record in most hospitalized ED patients >= 70 years. In addition, the 21% with a normal SBP at ED presentation had a negative Delta SBP and these patients had an increased risk for 30-day mortality. As a result, Delta SBP may contribute to improved risk stratification and may help to recognize hypotension in older patients. Show less
Mol, J. de; Kuiper, J.; Tsiantoulas, D.; Foks, A.C. 2021
Aging is considered to be an important risk factor for several inflammatory diseases. B cells play a major role in chronic inflammatory diseases by antibody secretion, antigen presentation and T... Show moreAging is considered to be an important risk factor for several inflammatory diseases. B cells play a major role in chronic inflammatory diseases by antibody secretion, antigen presentation and T cell regulation. Different B cell subsets have been implicated in infections and multiple autoimmune diseases. Since aging decreases B cell numbers, affects B cell subsets and impairs antibody responses, the aged B cell is expected to have major impacts on the development and progression of these diseases. In this review, we summarize the role of B cells in health and disease settings, such as atherosclerotic disease. Furthermore, we provide an overview of age-related changes in B cell development and function with respect to their impact in chronic inflammatory diseases. Show less
Panagiotou, M.; Michel, S.; Meijer, J.H.; Deboer, T. 2021
Aging is a multifactorial process likely stemming from damage accumulation and/or a decline in maintenance and repair mechanisms in the organisms that eventually determine their lifespan. In our... Show moreAging is a multifactorial process likely stemming from damage accumulation and/or a decline in maintenance and repair mechanisms in the organisms that eventually determine their lifespan. In our review, we focus on the morphological and functional alterations that the aging brain undergoes affecting sleep and the circadian clock in both human and rodent models. Although both species share mammalian features, differences have been identified on several experimental levels, which we outline in this review. Additionally, we delineate some challenges on the preferred analysis and we suggest that a uniform route is followed so that findings can be smoothly compared. We conclude by discussing potential interventions and highlight the influence of physical exercise as a beneficial lifestyle intervention, and its effect on healthy aging and longevity. We emphasize that even moderate age-matched exercise is able to ameliorate several aging characteristics as far as sleep and circadian rhythms are concerned, independent of the species studied. Show less
