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1.
Sci Rep ; 11(1): 4326, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619309

RESUMO

Mosaicism in blood varies with age, and cross-sectional studies indicate that for women, skewness of X-chromosomal mosaicism increases with age. This pattern could, however, also be due to less X-inactivation in more recent birth cohorts. Skewed X-chromosome inactivation was here measured longitudinally by the HUMARA assay in 67 septuagenarian and octogenarian women assessed at 2 time points, 10 years apart, and in 10 centenarian women assessed at 2 time points, 2-7 years apart. Skewed X-chromosome inactivation was also compared in 293 age-matched septuagenarian twins born in 1917-1923 and 1931-1937, and 212 centenarians born in 1895, 1905 and 1915. The longitudinal study of septuagenarians and octogenarians revealed that 16% (95% CI 7-29%) of the women developed skewed X-inactivation over a 10-year period. In the cross-sectional across-birth cohort study, the earlier-born septuagenarian (1917-1923) and centenarian women (1895) had a higher degree of skewness than the respective recent age-matched birth cohorts, which indicates that the women in the more recent cohorts, after the age of 70, had not only changed degree of skewness with age, they had also undergone less age-related hematopoietic sub-clone expansion. This may be a result of improved living conditions and better medical treatment in the more recent birth cohorts.

2.
Eur J Public Health ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33615329

RESUMO

BACKGROUND: As populations age, the possible consequences of increased frailty are a major concern for the health sector. Here, we investigate how life expectancy with and without frailty has changed during a 10-11-year-period across Europe. METHODS: The Sullivan method was used to investigate changes in life expectancy with and without frailty in 10 European countries. Frailty status (non-frail, pre-frail and frail) was determined by use of the Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI). Data on frailty prevalence was obtained from 21 698 individuals in wave 1 (2004-05) and 38 859 individuals in wave 6 (2015) of the SHARE. Information on mortality was obtained from the Eurostat Database. RESULTS: In 2015, women aged 70 spent 25.0% (95% CI: 24.0-26.1) of their remaining life expectancy in a frail state, and the number for men was 11.5% (95% CI: 10.7-12.3). Southern Europeans spent 24.2% (95% CI: 22.9-25.4) of their remaining life expectancy in a frail state and the numbers for Central Europeans and Northern Europeans were 17.0% (95% CI: 16.0-17.9) and 12.2% (95% CI: 10.9-13.5), respectively. From 2004-05 to 2015, life expectancy increased by 1.1 years (from 15.3 to 16.4 years) for 70-year-old Europeans. Similarly, non-frail life expectancy increased by 1.1 years (95% CI: 0.8-1.4), whereas no significant changes in life expectancy in frail states were observed. CONCLUSIONS: This study suggests that Europeans today spend more years in a non-frail state than Europeans did 10-11 years ago. Our findings reflect a considerable inequality by gender and region.

3.
Aging Cell ; 20(2): e13293, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528912

RESUMO

Privileged by rapid increase in available epigenomic data, epigenome-wide association studies (EWAS) are to make a profound contribution to understand the molecular mechanism of DNA methylation in cognitive aging. Current statistical methods used in EWAS are dominated by models based on multiple assumptions, for example, linear relationship between molecular profiles and phenotype, normal distribution for the methylation data and phenotype. In this study, we applied an assumption-free method, the generalized correlation coefficient (GCC), and compare it to linear models, namely the linear mixed model and kinship model. We use DNA methylation associated with a cognitive score in 400 and 206 twins as discovery and replication samples respectively. DNA methylation associated with cognitive function using GCC, linear mixed model, and kinship model, identified 65 CpGs (p < 1e-04) from discovery sample displaying both nonlinear and linear correlations. Replication analysis successfully replicated 9 of these top CpGs. When combining results of GCC and linear models to cover diverse patterns of relationships, we identified genes like KLHDC4, PAPSS2, and MRPS18B as well as pathways including focal adhesion, axon guidance, and some neurological signaling. Genomic region-based analysis found 15 methylated regions harboring 11 genes, with three verified in gene expression analysis, also the 11 genes were related to top functional clusters including neurohypophyseal hormone and maternal aggressive behaviors. The GCC approach detects valuable methylation sites missed by traditional linear models. A combination of methylation markers from GCC and linear models enriched biological pathways sensible in neurological function that could implicate cognitive performance and cognitive aging.

4.
Mech Ageing Dev ; : 111463, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33607172

RESUMO

Cognitive function is a substantially heritable trait related to numerous important life outcomes. Several genome-wide association studies of cognitive function have in recent years led to the identification of thousands of significantly associated loci and genes. Individuals included in these studies have rarely been nonagenarians and centenarians, and since cognitive function is an important component of quality of life for this rapidly expanding demographic group, there is a need to explore genetic factors associated with individual differences in cognitive function at advanced ages. In this study, we pursued this by performing a genome-wide association study of cognitive function in 490 long-lived Danes (age range 90.1-100.8 years). While no genome-wide significant SNPs were identified, suggestively significant SNPs (P < 1 × 10-5) were mapped to several interesting genes, including ZWINT, CELF2, and DNAH5, and the glutamate receptor genes GRID2 and GRM7. Additionally, results from a gene set over-representation analysis indicated potential roles of gene sets related to G protein-coupled receptor (GPCR) signaling, interaction between L1 and ankyrins, mitogen-activated protein kinase (MAPK) signaling, RNA degradation, and cell cycle. Larger studies are needed to shed further light on the possible importance of these suggestive genes and pathways in cognitive function in nonagenarians and centenarians.

5.
Clin Epigenetics ; 13(1): 35, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588926

RESUMO

BACKGROUND: Epigenetic inactivation of O6-methylguanine DNA-methyltransferase (MGMT) is associated with increased sensitivity to alkylating chemotherapeutic agents in glioblastoma patients. The genetic background underlying MGMT gene methylation may explain individual differences in treatment response and provide a clue to a personalized treatment strategy. Making use of the longitudinal twin design, we aimed, for the first time, to estimate the genetic contributions to MGMT methylation in a Danish twin cohort. METHODS: DNA-methylation from whole blood (18 monozygotic (MZ) and 25 dizygotic (DZ) twin pairs) repeated 10 years apart from the Longitudinal Study of Aging Danish Twins (LSADT) were used to search for genetic and environmental contributions to DNA-methylation at 170 CpG sites of across the MGMT gene. Both univariate and bivariate twin models were applied. The intraclass correlations, performed on cross-sectional data (246 MZ twin pairs) from an independent study population, the Middle-Aged Danish Twins (MADT), were used to assess the genetic influence at each CpG site of MGMT for replication. RESULTS: Univariate twin model revealed twelve CpG sites showing significantly high heritability at intake (wave 1, h2 > 0.43), and seven CpG sites with significant heritability estimates at end of follow-up (wave 2, h2 > 0.5). There were six significant CpG sites, located at the gene body region, that overlapped among the two waves (h2 > 0.5), of which five remained significant in the bivariate twin model, which was applied to both waves. Within MZ pair correlation in these six CpGs from MADT demarks top level of genetic influence. There were 11 CpGs constantly have substantial common environmental component over the 10 years. CONCLUSIONS: We have identified 6 CpG sites linked to the MGMT gene with strong and persistent genetic control based on their DNA methylation levels. The genetic basis of MGMT gene methylation could help to explain individual differences in glioblastoma treatment response and most importantly, provide references for mapping the methylation Quantitative Trait Loci (meQTL) underlying the genetic regulation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33491046

RESUMO

Despite enormous research efforts, the genetic component of longevity has remained largely elusive. The investigation of common variants, mainly located in intronic or regulatory regions, has yielded only little new information on the heritability of the phenotype. Here, we performed a chip-based exome-wide association study investigating 62,488 common and rare coding variants in 1,248 German long-lived individuals, including 599 centenarians and 6,941 younger controls (age < 60 years). In a single-variant analysis, we observed an exome-wide significant association between rs1046896 in the gene fructosamine-3-kinase-related-protein (FN3KRP) and longevity. Noteworthy, we found the longevity allele C of rs1046896 to be associated with an increased FN3KRP expression in whole blood; a database look-up confirmed this effect for various other human tissues. A gene-based analysis, in which potential cumulative effects of common and rare variants were considered, yielded the gene phosphoglycolate phosphatase (PGP) as another potential longevity gene, though no single variant in PGP reached the discovery P-value (1x10E-04). Furthermore, we validated the previously reported longevity locus cyclin dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1). Replication of our results in a French longevity cohort was only successful for rs1063192 in CDKN2B-AS1. In conclusion, we identified two new potential candidate longevity genes, FN3KRP and PGP which may influence the phenotype through their role in metabolic processes, i.e. the reverse glycation of proteins (FN3KRP) and the control of glycerol-3-phosphate levels (PGP).

7.
Wien Klin Wochenschr ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351155

RESUMO

AIM: To examine the magnitude of sex differences in survival from the coronavirus disease 2019 (COVID-19) in Europe across age groups and regions. We hypothesized that men have a higher mortality than women at any given age but that sex differences will decrease with age as only the healthiest men survive to older ages. METHODS: We used population data from the Institut National D'Études Démographiques on cumulative deaths due to COVID-19 from February to June 2020 in 10 European regions: Denmark, Norway, Sweden, The Netherlands, England and Wales, France, Germany, Italy, Spain and Portugal. For each region, we calculated cumulative mortality rates stratified by age and sex and corresponding relative risks for men vs. women. RESULTS: The relative risk of dying from COVID-19 was higher for men than for women in almost all age groups in all regions. The overall relative risk ranged from 1.11 (95% confidence interval, CI 1.01-1.23) in Portugal to 1.54 (95% CI 1.49-1.58) in France. In most regions, sex differences increased until the ages of 60-69 years, but decreased thereafter with the smallest sex difference at age 80+ years. CONCLUSION: Despite variability in data collection and time coverage among regions, the study showed an overall similar pattern of sex differences in COVID-19 mortality in Europe.

8.
Behav Genet ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33190169

RESUMO

Education has been suggested to be possibly the most consistent, robust, and durable method available for raising intelligence, but little is known about the genetic and environmental interplay underlying this association. Therefore, we investigated how school achievement, as measured by grade point average in lower secondary school at 15 years of age, moderated intelligence variation in young adulthood. The sample consisted of all Danish male twin pairs who had left lower secondary school since 2002 and appeared, typically at age 18, before a draft board through 2015 (N = 2660). Shared environmental variance unique to intelligence (10% of total variance) was found to be greater among individuals with poor school achievement. However, school achievement did not moderate the genetic influences or the non-shared environmental influences on intelligence. We discuss the implications of this in light of the constraints imposed by the statistical models we used.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33170216

RESUMO

BACKGROUND: Lower physical activity levels and greater fatigability contribute independently to slower gait speed in older adults. However, to fully understand the bidirectional relations between physical activity and fatigability, and to inform potential intervention strategies, we examined whether physical activity or fatigability explains more of the other factor's association on slower gait speed. METHODS: Two generations (probands and offspring) of older adults (N=2,079, mean age 73.0±10.0 years, 54.2% women, 99.7% white) enrolled in the Long Life Family Study were assessed at Visit 2 (2014-2017). Self-reported physical activity was measured with the Framingham Physical Activity Index, and perceived physical fatigability using the Pittsburgh Fatigability Scale. Statistical mediation analyses were conducted separately by generation with linear mixed-effect models accounting for family relatedness, and adjusted for demographics, health conditions, field center. RESULTS: Greater perceived physical fatigability explained the association of lower physical activity on slower gait speed via a 22.5% attenuation of the direct association (95% CI: 15.0%, 35.2%) for the probands and 39.5% (95% CI: 22.8%, 62.6%) for the offspring. Whereas, lower physical activity explained the association of greater perceived fatigability on slower gait speed via a 22.5% attenuation of the direct association (95% CI: 13.4%, 32.8%) for the probands and 6.7% (95% CI: 3.8%, 15.4%) for the offspring. CONCLUSIONS: Our findings suggest that the impact of greater perceived physical fatigability on the association between lower physical activity and slower gait speed differs between younger-old and middle-to-oldest old adults, indicating perceived physical fatigability as a potential mediator in the disablement pathway.

10.
Mol Psychiatry ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219357

RESUMO

Depression and cardiovascular disease (ischemic heart disease and stroke) are associated in a bidirectional manner. Their relatively high heritability has led to the hypothesis that this co-occurrence is related to shared familial and genetic factors; this study aims to test this hypothesis. We included 23,498 monozygotic and 39,540 same-sex dizygotic twins from the Danish Twin Registry followed from January 1977 until December 2011 in nationwide Danish registries. We used survival analyses accounting for censoring and competing risk of death to estimate cumulative incidence, casewise concordance, relative recurrence risk, and heritability of the co-occurrence of depression and cardiovascular disease by age using monozygotic and same-sex dizygotic twin pairs. The casewise concordance of ischemic heart disease or stroke in twins whose co-twin was diagnosed with depression was at all ages similar for the monozygotic and dizygotic twin pairs and to the cumulative incidence of ischemic heart disease or stroke, respectively, in the entire twin population. A similar pattern was seen in analyses of depression risk given the co-twin being diagnosed with ischemic heart disease or stroke. Relative recurrence risk and heritability estimates were also of modest size and with confidence intervals including unity. Results were similar after stratification by gender as well as when redefining depression to include the use of antidepressant medication from 1995. Our findings do not support that co-occurrence between depression and cardiovascular disease is explainable by shared genetic factors, nor did we find strong evidence of a familial effect.

11.
Aging (Albany NY) ; 12(22): 22457-22494, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232274

RESUMO

Despite a strong genetic background in cognitive function only a limited number of single nucleotide polymorphisms (SNPs) have been found in genome-wide association studies (GWASs). We hypothesize that this is partially due to mis-specified modeling concerning phenotype distribution as well as the relationship between SNP dosage and the level of the phenotype. To overcome these issues, we introduced an assumption-free method based on generalized correlation coefficient (GCC) in a GWAS of cognitive function in Danish and Chinese twins to compare its performance with traditional linear models. The GCC-based GWAS identified two significant SNPs in Danish samples (rs71419535, p = 1.47e-08; rs905838, p = 1.69e-08) and two significant SNPs in Chinese samples (rs2292999, p = 9.27e-10; rs17019635, p = 2.50e-09). In contrast, linear models failed to detect any genome-wide significant SNPs. The number of top significant genes overlapping between the two samples in the GCC-based GWAS was higher than when applying linear models. The GCC model identified significant genetic variants missed by conventional linear models, with more replicated genes and biological pathways related to cognitive function. Moreover, the GCC-based GWAS was robust in handling correlated samples like twin pairs. GCC is a useful statistical method for GWAS that complements traditional linear models for capturing genetic effects beyond the additive assumption.

12.
Epigenomics ; 12(17): 1531-1541, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32901529

RESUMO

Aim: Many efforts have been deployed to identify genetic variants associated with BMI. Alternatively, we explore epigenetic contribution to BMI variation by focusing on long noncoding RNAs (lncRNAs) which represents a key layer of epigenetic control. Materials & methods: We analyzed lncRNA expression in whole blood of 229 monozygotic twin pairs in association with BMI using generalized estimating equations. Results & conclusion: Six lncRNA probes were identified as significant (false discovery rate <0.05), with BMI showing causal effects on the expression of the significant lncRNAs. Functional annotation of differential profiles identified Gene ontology biological processes including kidney development, regulations of lipid biosynthetic process, circadian rhythm, notch signaling, etc. Whole blood lncRNAs are significantly expressed in response to BMI variation.

13.
Scand J Public Health ; : 1403494820953322, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880216

RESUMO

Aim: Our aim was to explore whether familial factors influence the risk of ischemic heart disease, stroke, and their co-occurrence. Methods: In total, 23,498 monozygotic and 39,540 same-sex dizygotic twins from the Danish Twin Registry were followed from 1977 to 2011 in the Danish National Patient Registry for ischemic heart disease and stroke. Time-to-event analyses accounting for censoring and competing risk of death were used to estimate familial risk (casewise concordance relative to the cumulative incidence) and heritability of ischemic heart disease, stroke, and the co-occurrence by age. Results: During follow-up, we observed 5561 and 4186 twin individuals with ischemic heart disease and stroke respectively, with 936 twin pairs concordant for ischemic heart disease and stroke. Familial risks were significant for both, with higher cumulative risks in monozygotic than in dizygotic twins. Estimates for heritability were significant for ischemic heart disease as well as for stroke diagnosed after the age of 80. The casewise concordance of ischemic heart disease in twins whose co-twin was diagnosed with stroke did not differ for monozygotic and dizygotic twins; however, from age 55 it was 10% higher than the cumulative risk in the overall twin cohort and was 25% higher at age 90. A similar pattern was seen for stroke following the co-twin's ischemic heart disease. Conclusions: As in previous studies, we found a higher heritability of ischemic heart disease than of stroke. There was a significant familial risk but no heritability for the co-occurrence of ischemic heart disease and stroke. The co-occurrence is therefore likely due to other shared familial than genetic factors, highlighting that preventive initiatives should target families rather than individuals.

14.
Aging Cell ; 19(10): e13228, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32886847

RESUMO

The familial resemblance in length of adult life is very modest. Studies of parent-offspring and twins suggest that exceptional health and survival have a stronger genetic component than lifespan generally. To shed light on the underlying mechanisms, we collected information on Danish long-lived siblings (born 1886-1938) from 659 families, their 5379 offspring (born 1917-1982), and 10,398 grandchildren (born 1950-2010) and matched background population controls through the Danish 1916 Census, the Civil Registration System, the National Patient Register, and the Register of Causes of Death. Comparison with the background, population revealed consistently lower occurrence of almost all disease groups and causes of death in the offspring and the grandchildren. The expected incidence of hospitalization for mental and behavioral disorders was reduced by half in the offspring (hazard ratio 0.53, 95% confidence interval 0.45-0.62) and by one-third in the grandchildren (0.69, 0.61-0.78), while the numbers for tobacco-related cancer were 0.60 (0.51-0.70) and 0.71 (0.48-1.05), respectively. Within-family analyses showed a general, as opposed to specific, lowering of disease risk. Early parenthood and divorce were markedly less frequent in the longevity-enriched families, while economic and educational differences were small to moderate. The longevity-enriched families in this study have a general health advantage spanning three generations. The particularly low occurrence of mental and behavioral disorders and tobacco-related cancers together with indicators of family stability and only modest socioeconomic advantage implicate behavior as a key mechanism underlying familial aggregation of exceptional health and survival.

15.
PLoS One ; 15(9): e0238912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997671

RESUMO

BACKGROUND: Population aging will pose huge challenges for healthcare systems and will require a promotion of positive attitudes towards older people and the encouragement of careers in geriatrics to attract young professionals into the field and to meet the needs of a rapidly growing number of old-aged patients. We describe the current demographic profile of hospital care use in Denmark and make projections for changes in the patient profile up to 2050. METHODS: The Danish population in 2013 (N = 5.63 million) was followed up for inpatient and emergency admissions recorded in Danish hospitals in 2013 using population-based registers. We combined age- and sex-specific hospital care use in 2013 with official population estimates to forecast the profile of hospital days up to 2050 with respect to age and sex. RESULTS: The total number of hospital days per year is projected to increase by 42% between 2013 and 2050, from 4.66 to 6.72 million days. While small changes are projected for the population aged 0-69, the largest change is projected to occur for the population aged 70+. The 2013 levels were 0.82 and 0.93 million days for men and women aged 70+, respectively. By 2050, these levels are projected to have reached 1.94 and 1.84 million days. While the population aged 70+ accounted for 37.5% of all days in 2013, its contribution is projected to increase to 56.2% by 2050. CONCLUSION: Our study shows one possible scenario for changes in the hospital days due to population aging by 2050: Assuming no changes in hospital care use over the forecast period, the absolute contribution of individuals aged 70+ to the total hospital days will more than double, and the relative contribution of persons aged 70+ will account for nearly 60% of all hospital days by 2050, being largest among men.


Assuntos
Previsões/métodos , Hospitalização/tendências , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores Sexuais , Adulto Jovem
16.
Res Sq ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32935092

RESUMO

Aim: International health authorities suggest that individuals aged 65 years and above and people with underlying comorbidities such as hypertension, chronic lung disease, cardiovascular disease, cancer, diabetes, and obesity are at increased risk of severe Coronavirus Disease 2019 (COVID-19); however, the prevalence of risk factors is unknown in many countries. Therefore, we aim to describe the distribution of these risk factors across Europe. Subject and Methods: Prevalence of risk factors for severe COVID-19 was identified based on interview for 73,274 Europeans aged 50+ participating in the Survey of Health, Ageing and Retirement in Europe (SHARE) in 2017. Burden of disease was estimated using population data from Eurostat. Results: A total of 75.3% of the study population (corresponding to app. 60 million European men and 71 million women) had at least one risk factor for severe COVID-19, 45.9% (app. 36 million men and 43 million women) had at least two factors and 21.2% (app. 17 million men and 20 million women) had at least three risk factors. The prevalences of underlying medical conditions ranged from 4.5% for cancer to 41.4% for hypertension, and the region-specific prevalence of having at least three risk factors ranged from 18.9% in Northern Europe to 24.6% in Eastern Europe. Conclusions: Information about the prevalences of risk factors might help authorities to identify the most vulnerable subpopulations with multiple risk factors of severe COVID-19 disease and thus to decide appropriate strategies to mitigate the pandemic.

17.
J Infect Dis ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909605

RESUMO

BACKGROUND: Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer with all-cause and cardiovascular mortality in 5 longitudinal cohorts. METHODS: Leiden Longevity Study, Prospective Study of Pravastatin in the Elderly at Risk, Longitudinal Study of Aging Danish Twins, and Leiden 85-plus Study were assessed at median (2.8-11.4 years) follow-up . Cox regression and random effects meta-analysis were used to estimate mortality risk dependent on CMV serostatus and/or IgG antibody titer, in quartiles after adjusting for confounders. RESULTS: CMV-seropositivity was seen in 47%-79% of 10 122 white community-dwelling adults aged 59-93 years. Of these, 3519 had died on follow-up (579 from cardiovascular disease). CMV seropositivity was not associated with all-cause (hazard ratio [HR], 1.05; 95% confidence interval [CI], .97-1.14) or cardiovascular mortality (HR, 0.97; 95% CI, .83-1.13). Subjects in the highest CMV IgG quartile group had increased all-cause mortality relative to CMV-seronegatives (HR, 1.16; 95% CI, 1.04-1.29) but this association lost significance after adjustment for confounders (HR, 1.13; 95% CI, .99-1.29). The lack of increased mortality risk was confirmed in subanalyses. CONCLUSIONS: CMV infection is not associated with all-cause or cardiovascular mortality in white community-dwelling older adults.

18.
Res Sq ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32839767

RESUMO

Aim: To examine the magnitude of sex differences in survival from the Coronavirus Disease 2019 (COVID-19) in Europe across age and countries. We hypothesise that men have higher mortality than women at any given age, but that sex differences will decrease with age as only the strongest men survive to older ages. Methods: We used population data from Institut National D'Études Démographiques on cumulative deaths due to COVID-19 from February to June 2020 in 10 European countries: Denmark, Norway, Sweden, The Netherlands, England & Wales, France, Germany, Italy, Spain and Portugal. For each country, we calculated cumulative mortality rates stratified by age and sex and corresponding relative risks for men vs. women. Results: The relative risk of dying from COVID-19 was higher for men than for women in almost all age groups in all countries. The overall relative risk ranged from 1.11 (95% CI 1.01-1.23) in Portugal to 1.54 (95% CI 1.49-1.58) in France. In most countries, sex differences increased until ages 60-69 years, but decreased thereafter with the smallest sex difference at ages 80+. Conclusions: Despite variability in data collection and time coverage among countries, we illustrate an overall similar pattern of sex differences in COVID-19 mortality in Europe.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32794566

RESUMO

BACKGROUND: Circulating levels of procollagen type III N-terminal peptide (P3NP) may reflect increased fibrosis of skeletal muscle and other tissues with aging. Herein, we tested if P3NP was associated with baseline and 7-year change in physical function. METHODS: Participants (n=400) were from the Long Life Family Study, a study of exceptional familial longevity. Plasma P3NP concentration was measured using a sandwich enzyme-linked immunosorbent assay (inter-assay CVs <5.5%). At baseline and 7-year follow-up visits, physical function was measured using the Short Physical Performance Battery (score 0-12), which consists of gait speed, balance, and chair-rise tests. Grip strength was measured using a handheld dynamometer. The association between log transformed P3NP and physical function was examined using Generalized Estimating Equations adjusted for familial relatedness, age, sex, height, weight, lifestyle characteristics, liver function, kidney function, lung function and chronic disease prevalence. RESULTS: Participants were aged 73.1 ± 15.2 years (range: 39-104), 54% female, had BMIs of 26.6 ± 4.3 kg/m2, and gait speeds of 1.0 ± 0.3 m/s. One standard deviation higher log-transformed P3NP was related to worse baseline SPPB score (ß=-0.9points), gait speed (ß=-0.05m/s), chair-rises per-second (ß=-0.46 chair-rises/10 seconds), and grip strength (ß=-2.0kg; all p<0.001). Higher P3NP was also associated with greater declines in gait speed (ß=-1.41, p<.001) and transitioning to being unable to perform chair-rises (ß=0.41, p<.001) after 7 years. CONCLUSION: Plasma P3NP may be a strong, novel biomarker of current and future physical function. Future research is needed to extend our findings to other cohorts and determine mechanisms underlying these associations.

20.
Aging (Albany NY) ; 12(14): 15157-15168, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652515

RESUMO

Long-lived individuals are central in studies of healthy longevity. However, few pro-longevity factors have been identified, presumably because of "phenocopies", i.e. individuals that live long by chance. Familial longevity cases may include less phenocopies than sporadic cases and provide better insights into longevity mechanisms. Here we examined whether long-lived female siblings have a better ability to avoid diseases at ages 65+ (proxy for "robustness") and/or survive to extreme ages (proxy for "resilience") compared to sporadic long-livers. A total of 1,156 long-lived female siblings were selected from three nationwide Danish studies and age-matched with sporadic long-lived female controls. Outcomes included cumulative incidence of common health disorders from age 65 and overall survival. Long-lived female siblings had lower risks of some but not all health conditions, most significantly, depression (OR=0.74; 95%CI=0.62-0.88), and less significantly hypertensive (OR=0.84; 95%CI=0.71-0.99) and cerebrovascular (OR=0.73; 95%CI=0.55-0.96) diseases. They also had consistently better survival to extreme ages (HR=0.71; 95%CI= 0.63-0.81) compared to sporadic long-livers. After adjustment for the diseases, the association with mortality changed only marginally suggesting central role of better physiological resilience in familial longevity. Due to their consistently better resilience, familial longevity cases could be more informative than sporadic cases for studying mechanisms of healthy longevity.

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