| 1. |
- Hagg, Sara, et al.
(författare)
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Age, Frailty, and Comorbidity as Prognostic Factors for Short-Term Outcomes in Patients With Coronavirus Disease 2019 in Geriatric Care
- 2020
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Ingår i: Journal of the American Medical Directors Association. - : ELSEVIER SCIENCE INC. - 1525-8610 .- 1538-9375. ; 21:11, s. 1555-1559
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To analyze whether frailty and comorbidities are associated with in-hospital mortality and discharge to home in older adults hospitalized for coronavirus disease 2019 (COVID-19). Design: Single-center observational study. Setting and Participants: Patients admitted to geriatric care in a large hospital in Sweden between March 1 and June 11, 2020; 250 were treated for COVID-19 and 717 for other diagnoses. Methods: COVID-19 diagnosis was clinically confirmed by positive reverse transcription polymerase chain reaction test or, if negative, by other methods. Patient data were extracted from electronic medical records, which included Clinical Frailty Scale (CFS), and were further used for assessments of the Hospital Frailty Risk Score (HFRS) and the Charlson Comorbidity Index (CCI). In-hospital mortality and home discharge were followed up for up to 25 and 28 days, respectively. Multivariate Cox regression models adjusted for age and sex were used. Results: Among the patients with COVID-19, in-hospital mortality rate was 24% and home discharge rate was 44%. Higher age was associated with in-hospital mortality (hazard ratio [HR] 1.05 per each year, 95% confidence interval [CI] 1.01.1.08) and lower probability of home discharge (HR 0.97, 95% CI 0.95.0.99). CFS (>5) and CCI, but not HFRS, were predictive of in-hospital mortality (HR 1.93, 95% CI 1.02.3.65 and HR 1.27, 95% CI 1.02.1.58, respectively). Patients with CFS >5 had a lower probability of being discharged home (HR 0.38, 95% CI 0.25.0.58). CCI and HFRS were not associated with home discharge. In general, effects were more pronounced in men. Acute kidney injury was associated with in-hospital mortality and hypertension with discharge to home. Other comorbidities (diabetes, cardiovascular disease, lung diseases, chronic kidney disease and dementia) were not associated with either outcome. Conclusions and Implications: Of all geriatric patients with COVID-19, 3 out of 4 survived during the study period. Our results indicate that in addition to age, the level of frailty is a useful predictor of short-term COVID-19 outcomes in geriatric patients. (C) 2020 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 2. |
- Hong, Mun-Gwan, et al.
(författare)
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Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality
- 2020
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Ingår i: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 3:10, s. e202000817-
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Tidskriftsartikel (refereegranskat)abstract
- Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50–92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10−6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12–1.39; P = 6.45 × 10−5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7–9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.
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| 3. |
- Karlsson, Ida K., et al.
(författare)
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Replicating associations between DNA methylation and body mass index in a longitudinal sample of older twins
- 2020
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Ingår i: International Journal of Obesity. - : Springer Nature. - 0307-0565 .- 1476-5497. ; 44:6, s. 1397-1405
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Tidskriftsartikel (refereegranskat)abstract
- Background:There is an important interplay between epigenetic factors and body weight, and previous work has identified ten sites where DNA methylation is robustly associated with body mass index (BMI) cross-sectionally. However, interpretation of the associations is complicated by the substantial changes in BMI often occurring in late-life, and the fact that methylation is often driven by genetic variation. This study therefore investigated the longitudinal association between these ten sites and BMI from midlife to late-life, and whether associations persist after controlling for genetic factors.Methods:We used data from 535 individuals (mean age 68) in the Swedish Adoption/Twin Study of Aging (SATSA) with longitudinal measures of both DNA methylation from blood samples and BMI, spanning up to 20 years. Methylation levels were measured with the Infinium Human Methylation 450K or Infinium MethylationEpic array, with seven of the ten sites passing quality control. Latent growth curve models were applied to investigate longitudinal associations between methylation and BMI, and between–within models to study associations within twin pairs, thus adjusting for genetic factors.Results:Baseline DNA methylation levels at five of the seven sites were associated with BMI level at age 65 (cg00574958 [CPT1A]; cg11024682 [SREBF1]), and/or change (cg06192883 [MYO5C]; cg06946797 [RMI2]; cg08857797 [VPS25]). For four of the five sites, the associations remained comparable within twin pairs. However, the effects of cg06192883 were substantially attenuated within pairs. No change in DNA methylation was detected for any of the seven evaluated sites.Conclusion:Five of the seven sites investigated were associated with late-life level and/or change in BMI. The effects for four of the sites remained similar when examined within twin pairs, indicating that the associations are mainly environmentally driven. However, the substantial attenuation in the association between cg06192883 and late-life BMI within pairs points to the importance of genetic factors in this association.
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| 4. |
- Li, Xia, et al.
(författare)
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Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up.
- 2020
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Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Biological age measurements (BAs) assess aging-related physiological change and predict health risks among individuals of the same chronological age (CA). Multiple BAs have been proposed and are well studied individually but not jointly. We included 845 individuals and 3973 repeated measurements from a Swedish population-based cohort and examined longitudinal trajectories, correlations, and mortality associations of nine BAs across 20 years follow-up. We found the longitudinal growth of functional BAs accelerated around age 70; average levels of BA curves differed by sex across the age span (50-90 years). All BAs were correlated to varying degrees; correlations were mostly explained by CA. Individually, all BAs except for telomere length were associated with mortality risk independently of CA. The largest effects were seen for methylation age estimators (GrimAge) and the frailty index (FI). In joint models, two methylation age estimators (Horvath and GrimAge) and FI remained predictive, suggesting they are complementary in predicting mortality.
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| 5. |
- Wang, Yunzhang
(författare)
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DNA methylation and aging : a longitudinal study of old Swedish twins
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- DNA methylation is a well-known biomarker of aging. Many previous studies have reported the change of DNA methylation patterns with age, and analyzed DNA methylation in association with aging outcomes. However, most publications were based on cross-sectional data while longitudinal evidence was largely missing. Hence, in this thesis, we used longitudinal measures of DNA methylation from the Swedish Adoption/Twin Study of Aging (SATSA) to comprehensively study the role of DNA methylation in aging. The first three studies in this thesis focus on different mechanisms of DNA methylation related to aging, including methylation level, methylation variability and epigenetic mutation. In Study I, we investigated the longitudinal change of methylation level with age from an epigenome-wide association study (EWAS) using a mixed effect model. We identified 1316 age-related CpGs and successfully validated them in two external cohorts. Further, we analyzed the methylation difference between paired twins at the same time-point, and found it increased with age. We also identified genetic effect on age-associated CpGs, but the effect was independent on age. In Study II, we first developed a method that could properly model the longitudinal change of methylation variability with age in simulated data. The method included a linear model to regress methylation on age, followed by a random intercept model to regress the absolute residuals on age. Next, we applied the method in an EWAS and identified 570 age-varying CpGs. The inter-individual variance of most CpGs increased with age longitudinally. In Study III, we comprehensively studied epigenetic mutations, which are extreme outliers in the distribution of methylation level. The number of epigenetic mutations significantly increased with age in our longitudinal data. We also identified other factors associated with epigenetic mutations, including sex, B cell, sample quality, cancer diagnosis and first genetic principal component. Further, we classified CpGs into frequent mutated CpGs, highly methylated outliers (HMO) and lowly methylated outliers (LMO), and found frequent HMOs were more related to biological factors. In the end, we validated epigenetic mutations using bisulfite pyrosequencing and proved that epigenetic mutations were persist and could accumulate in aging. In Study IV, we performed an EWAS to analyze methylation levels, methylation variability and epigenetic mutations in association with mortality. We observed age-varying effect of methylation level on all-cause mortality which may explain the poor replication in previous studies. We also identified CpGs of cancer genes related to death from cancer. In the end, we provided evidence that methylation variability could predict all-cause mortality.
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