With the continued rise in the proportion of the oldest-old in high-income countries, it is of interest to know whether the functional health of today's oldest-olds is better or worse than in ...previous cohorts. Using two Danish centenarian birth cohorts born 20 years apart we aimed at investigating if the later born cohort had better functioning in terms of activities of daily living (ADL).
Identification, methodology, and assessment instruments were identical in the 1895-West and 1915-West Birth Cohort Studies: All persons living in the western part of Denmark and turning 100 years old in 1995 and 2015, respectively. Data were collected through structured in-home interviews. Participation rates were 74% (n = 106) and 79% (n = 238), respectively.
The proportion of nondisabled women of the 1915-West cohort was more than twice as high compared to the 1895-West cohort and with corresponding lower proportions of moderately and severely disabled persons (17% vs 7%, 33% vs 40% and 50% vs 53% in the 1915-West and 1895-West cohorts, respectively, p = .047). Only nonsignificant improvements were seen among men in the 1915-West cohort. In both sexes, considerably higher proportions of the latest cohort used assistive devices than the former (statistically significant for the majority of assistive devices).
This comparative study shows improvements in reported ADL in the later born cohort of centenarians, even though only significant among women. As women constitute the majority of the oldest-olds, our findings are encouraging from a public health care view.
Summary
Exogenous and endogenous damage to DNA is constantly challenging the stability of our genome. This DNA damage increase the frequency of errors in DNA replication, thus causing point mutations ...or chromosomal rearrangements and has been implicated in aging, cancer, and neurodegenerative diseases. Therefore, efficient DNA repair is vital for the maintenance of genome stability. The general notion has been that DNA repair capacity decreases with age although there are conflicting results. Here, we focused on potential age‐associated changes in DNA damage response and the capacities of repairing DNA single‐strand breaks (SSBs) and double‐strand breaks (DSBs) in human peripheral blood mononuclear cells (PBMCs). Of these lesions, DSBs are the least frequent but the most dangerous for cells. We have measured the level of endogenous SSBs, SSB repair capacity, γ‐H2AX response, and DSB repair capacity in a study population consisting of 216 individuals from a population‐based sample of twins aged 40–77 years. Age in this range did not seem to have any effect on the SSB parameters. However, γ‐H2AX response and DSB repair capacity decreased with increasing age, although the associations did not reach statistical significance after adjustment for batch effect across multiple experiments. No gender differences were observed for any of the parameters analyzed. Our findings suggest that in PBMCs, the repair of SSBs is maintained until old age, whereas the response to and the repair of DSBs decrease.
Background
Fatigue, inflammation, and physical activity (PA) are all independently associated with gait speed, but their directionality is not fully elucidated.
Aims
Evaluate the bidirectional ...associations amongst fatigue, inflammation, and PA on gait speed.
Methods
This cross sectional study included probands (
n
= 1280, aged 49–105) and offspring (
n
= 2772, aged 24–88) in the Long Life Family Study. We assessed gait speed, fatigue with the question “I could not get going”, inflammation using fasting interleukin-6 (IL-6) and high sensitivity C-reactive protein (CRP), and self-reported PA as walking frequency in the past two weeks. The two generations were examined separately using linear mixed modeling.
Results
Lower fatigue, lower IL-6, and greater PA were all associated with faster gait speed in both generations (all
p
< 0.05); lower CRP was only associated with faster gait speed in the offspring. PA explained the association of fatigue and gait speed via a 16.1% (95% CI 9.7%, 26.7%) attenuation of the direct associations for the probands and 9.9% (95% CI 6.3%, 18.8%) in the offspring. In addition, IL-6 explained more of the association of fatigue and gait speed than the association between PA and gait speed, via a 14.9% (95% CI 9.2%, 23.4%) attenuation of the direct association in the offspring only.
Discussion
Results revealed a potential directionality from fatigue to IL-6 to PA that may lead to faster gait speed. Future work should examine these relationships longitudinally to establish temporality and causality.
Conclusions
Our findings support a signal that lowering fatigue and inflammation and increasing physical activity may delay functional decline.
The aim of this study was to investigate the risk of psychiatric diagnoses in individuals with non-syndromic oral clefts (OC) compared with individuals without OC, including ages from 1 to 76 years.
...Linking four Danish nationwide registers, we investigated the risk of psychiatric diagnoses at Danish psychiatric hospitals during the period 1969-2012 for individuals born with non-syndromic OC in Denmark 1936-2009 compared with a cohort of 10 individuals without OC per individual with OC, matched by sex and birth year. The sample included 8,568 individuals with OC, observed for 247,821 person-years, and 85,653 individuals without OC followed for 2,501,129 person-years.
A total of 953 (11.1%) of the individuals with OC (9.6% for cleft lip (CL), 10.8% for cleft lip and palate (CLP) and 13.1% for cleft palate (CP)) and 8,117 (9.5%) in the comparison group had at least one psychiatric diagnosis. Cox proportional hazard regression model revealed that individuals with OC had significantly higher risk of a psychiatric diagnosis (hazard ratio (HR) = 1.19, 95% CI: 1.12-1.28). When examining cleft type, no difference was found for CL (HR = 1.03, 95% CI: 0.90-1.17), but CLP was associated with a small increased risk (HR = 1.13, 95% CI: 1.01-1.26), whereas individuals with CP had the largest increased risk (HR = 1.45, 95% CI: 1.30-1.62). The largest differences were found in schizophrenia-like disorders, mental retardation and pervasive developmental disorders, but we found no increased risk of mood disorders and anxiety-related disorders.
Individuals with non-syndromic OC had significantly higher risk of psychiatric diagnoses compared with individuals without OC. However, the elevated risk was observed for individuals with CLP and CP but not for individuals with CL and the absolute risk increase was modest.
The present study investigated the Danish secular trend of intelligence test scores among young men born between 1940 and 2000, as well as the possible associations of birth cohort changes in family ...size, nutrition, education, and intelligence test score variability with the increasing secular trend. The study population included all men born from 1940 to 2000 who appeared before a draft board before 2020 (N = 1,556,770). At the mandatory draft board examination, the approximately 19-year-old men underwent a medical examination and an intelligence test. In the statistical analyses, the IQ mean and standard deviation (SD) were estimated separately for each of the included annual birth cohorts based on information from birth cohorts with available total intelligence test scores for all tested individuals (i.e. 1940-1958 and 1987-2000; the mean and SD were interpolated for the intermediate birth cohorts). Moreover, the possible associations with birth cohort changes in family size, height as a proxy for nutritional status, education, and IQ variability were investigated among those birth cohorts for whom a secular increase in intelligence test scores was found. The results showed that the estimated mean IQ score increased from a baseline set to 100 (SD: 15) among individuals born in 1940 to 108.9 (SD: 12.2) among individuals born in 1980, since when it has decreased. Focusing on the birth cohorts of 1940-1980, for whom a secular increase in intelligence test scores was found, birth cohort changes in family size, height, and education explained large proportions of the birth cohort variance in mean intelligence test scores, suggesting that these factors may be important contributors to the observed Flynn effect in Denmark.
Previously we have shown that nonsyndromic cleft lip with or without cleft palate (NSCL/P) (1) is strongly associated with SNPs in IRF6 (interferon regulatory factor 6) (2). Here, we use multispecies ...sequence comparisons to identify a common SNP (rs642961, G > A) in a newly identified IRF6 enhancer. The A allele is significantly overtransmitted (P = 1 x 10.sup.-11) in families with NSCL/P, in particular those with cleft lip but not cleft palate. Further, there is a dosage effect of the A allele, with a relative risk for cleft lip of 1.68 for the AG genotype and 2.40 for the AA genotype. EMSA and ChIP assays demonstrate that the risk allele disrupts the binding site of transcription factor AP-2α and expression analysis in the mouse localizes the enhancer activity to craniofacial and limb structures. Our findings place IRF6 and AP-2α in the same developmental pathway and identify a high-frequency variant in a regulatory element contributing substantially to a common, complex disorder.
This study compares handgrip strength and its association with mortality across studies conducted in Moscow, Denmark, and England.
The data collected by the Study of Stress, Aging, and Health in ...Russia, the Study of Middle-Aged Danish Twins and the Longitudinal Study of Aging Danish Twins, and the English Longitudinal Study of Ageing was utilized.
Among the male participants, the age-standardized grip strength was 2 kg and 1 kg lower in Russia than in Denmark and in England, respectively. The age-standardized grip strength among the female participants was 1.9 kg and 1.6 kg lower in Russia than in Denmark and in England, respectively. In Moscow, a one-kilogram increase in grip strength was associated with a 4% (hazard ratio HR = 0.96, 95% confidence interval CI: 0.94, 0.99) reduction in mortality among men and a 10% (HR = 0.90, 95%CI: 0.86, 0.94) among women. Meanwhile, a one-kilogram increase in grip strength was associated with a 6% (HR = 0.94, 95%CI: 0.93, 0.95) and an 8% (HR = 0.92, 95%CI: 0.90, 0.94) decrease in mortality among Danish men and women, respectively, and with a 2% (HR = 0.98, 95%CI: 0.97, 0.99) and a 3% (HR = 0.97, 95%CI: 0.95, 0.98) reduction in mortality among the English men and women, respectively.
The study suggests that, although absolute grip strength values appear to vary across the Muscovite, Danish, and English samples, the degree to which grip strength is predictive of mortality is comparable across national populations with diverse socioeconomic and health profiles and life expectancy levels.
•We studied perceived age and DNA methylation age in 180 elderly Danish twins.•We did not see an association between these when correcting for gender.•Intrapair-analysis did not reveal a significant ...association either.•Predicting perceived age with CpGs underlying DNAm age had low prediction quality.•Our results suggest that perceived age and DNAm age capture different ageing aspects.
Perceived age is an easily accessible biomarker of aging. Here, we studied its relation to DNA methylation age (DNAm age) as introduced in (Horvath, 2013) in 180 elderly Danish twins. We found perceived age and DNAm age to be associated with chronological age (P=0.04 resp. P=2.2e-10) when correcting for gender, but did not see an association between perceived age and DNAm age (P=0.44). Intrapair-analysis showed that the proportion of pairs where the twin with the highest perceived age also had the highest DNAm age was not different from 0.5 (P=1), and we did not see a trend when dividing pairs according to their difference in perceived age (P=0.36). Hence, intrapair analysis did not reveal links between perceived age and DNAm age. Moreover, none of the 353 CpGs underlying DNAm age was individually associated with perceived age after correction for multiple-testing (P>6e-4, FDR>0.21). Finally, when constructing an epigenetic signature based on these CpGs to predict perceived age, we only found a correlation of 0.18 (95%CI: −0.06 to 0.40) and a mean square error of 13.6 years2 between observed and predicted values in the test dataset, indicating poor predictive strength. Altogether, our results suggest that perceived age and DNAm age capture different aging aspects.
Context:
Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by ...hyperthyroidism per se, comorbidity, and/or genetic confounding.
Objective:
The objective of the study was to investigate whether hyperthyroidism is associated with an increased mortality and, if so, whether the association is influenced by comorbidity and/or genetic confounding.
Methods:
This was an observational cohort study using record-linkage data from nationwide Danish health registers. We identified 4850 singletons and 926 twins from same-sex pairs diagnosed with hyperthyroidism. Each case was matched with four controls for age and gender. The Charlson score was calculated from discharge diagnoses on an individual level to measure comorbidity. Cases and controls were followed up for a mean of 10 yr (range 0–31 yr), and the hazard ratio (HR) for mortality was calculated using Cox regression analyses.
Results:
In singletons there was a significantly higher mortality in individuals diagnosed with hyperthyroidism than in controls HR 1.37; 95% confidence interval (CI) 1.30–1.46. This persisted after adjustment for preexisting comorbidity (HR 1,28; 95% CI 1.21–1.36). In twin pairs discordant for hyperthyroidism (625 pairs), the twin with hyperthyroidism had an increased mortality compared with the corresponding cotwin (HR 1.43; 95% CI 1.09–1.88). However, this was found only in dizygotic pairs (HR 1.80; 95% CI 1.27–2.55) but not in monozygotic pairs (HR 0.95; 95% CI 0.60–1.50).
Conclusions:
Hyperthyroidism is associated with an increased mortality independent of preexisting comorbidity. The study of twin pairs discordant for hyperthyroidism suggests that genetic confounding influences the association between hyperthyroidism and mortality.
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