Large common deletions associate with mortality at old age.
Ontology highlight
ABSTRACT:
SUBMITTER: Kuningas M
PROVIDER: S-EPMC3188993 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectivesTo assess the association between multiple indicators of socioeconomic position and dementia-related death, and to estimate the contribution of dementia to socioeconomic differences in overall mortality at older ages.DesignProspective population-based register study.SettingFinland.Participants11% random sample of the population aged 70-87 years resident in Finland at the end of year 2000 (n=54 964).Main outcome measureIncidence rates, Kaplan-Meier survival probabilities and Cox regression HRs of dementia mortality in 2001-2016 by midlife education, occupational social class and household income measured at ages 53-57 years.ResultsDuring the 528 387 person-years at risk, 11 395 individuals died from dementia (215.7 per 10 000 person-years). Lower midlife education, occupational social class and household income were associated with higher dementia mortality, and the differences persisted to the oldest old ages. Compared with mortality from all other causes, however, the socioeconomic differences emerged later. Dementia accounted for 28% of the difference between low and high education groups in overall mortality at age 70+ years, and for 21% of the difference between lowest and highest household income quintiles. All indicators of socioeconomic position were independently associated with dementia mortality, low household income being the strongest independent predictor (HR=1.24, 95% CI 1.16 to 1.32), followed by basic education (HR=1.14, 1.06 to 1.23). Manual occupational social class was related to a 6% higher hazard (HR=1.06, 1.01 to 1.11) compared with non-manual social class. Adjustment for midlife economic activity, baseline marital status and chronic health conditions attenuated the excess hazard of low midlife household income, although significant effects remained.ConclusionSeveral indicators of socioeconomic position predict dementia mortality independently and socioeconomic inequalities persist into the oldest old ages. The results demonstrate that dementia is among the most important contributors to socioeconomic inequalities in overall mortality at older ages.
| S-EPMC6955538 | biostudies-literature
Project description:Guided by a convoy model of social relations, this study investigates the relationships between grandparenting status, social relations, and mortality among community-dwelling grandparents age 65 and older who are caring for their grandchildren. The data were drawn from the 2008 and 2016 waves of the Health and Retirement Study (N = 564). Latent class analysis was used to identify the social network structure based on six indicators of interpersonal relationships and activities. A series of hierarchical Weibull hazard models estimated the associations between grandparent caregiving, social relations, and mortality risk. Results of survival analyses indicate that co-parenting and custodial grandparents had higher all-cause mortality risk than grandparents who babysat occasionally; however, for custodial grandparents, the association was not significant once social relation variables were added to the model. This study suggests that community-based support may be beneficial to older grandparents and improved relationship quality is integral to the well-being of older adults.
| S-EPMC10784123 | biostudies-literature
Project description:This paper aims to improve the accuracy of parametric extrapolations of the death rates into old age by constraining the extrapolation model on presumed life expectancy at old age. Such a task is particularly important in cases where the data quality at old age, in particular the age exaggeration, is not sufficient for reliable mortality estimates. Our tests are based on period data from the Human Mortality Database and the use of the Horiuchi-Coale and Mitra formulas for reducing the bias of life expectancy in the open age interval. We show that extrapolation accuracy is substantially improved when the extrapolation is constrained by either the empirical life expectancy or the Horiuchi-Coale or Mitra estimates. Unconstrained extrapolations and those constrained by conventional life table estimates of life expectancy in the open age interval show substantial biases and should be avoided. Combining extrapolation with life expectancy estimates which are robust to the effects of age exaggeration appears to be a valuable way of improving mortality estimation.
| S-EPMC6096879 | biostudies-literature
Project description:Americans experience higher mortality than their peers in other high-income countries for most of the life course, but recent work has shown that at the oldest ages they experience a mortality advantage- a phenomenon we call the "US mortality crossover." In this paper we document the crossover and time trends thereof. We find that the age of crossover increases linearly by about 0.5 years per year, a pattern of changes that, to our knowledge, has not been identified before. We then interrogate several potential explanations for a steadily increasing crossover age. While none is completely satisfactory, we rule out differential age misstatement, selection, and access to and quality of health care. We find that the most plausible explanations involve the deleterious effects of differential smoking and obesity but we are unable to adjudicate more precisely if either of these independently or in combination explain the phenomenon.
| S-EPMC6748636 | biostudies-literature
Project description:BackgroundSurvival to old ages is increasing in many African countries. While demographic tools for estimating mortality up to age 60 have improved greatly, mortality patterns above age 60 rely on models based on little or no demographic data. These estimates are important for social planning and demographic projections. We provide direct estimations of older-age mortality using survey data.MethodsSince 2005, nationally representative household surveys in ten sub-Saharan countries record counts of living and recently deceased household members: Burkina Faso, Côte d'Ivoire, Ethiopia, Namibia, Nigeria, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe. After accounting for age heaping using multiple imputation, we use this information to estimate probability of death in 5-year intervals ((5)q(x)). We then compare our (5)q(x) estimates to those provided by the World Health Organization (WHO) and the United Nations Population Division (UNPD) to estimate the differences in mortality estimates, especially among individuals older than 60 years old.FindingsWe obtained information on 505,827 individuals (18.4% over age 60, 1.64% deceased). WHO and UNPD mortality models match our estimates closely up to age 60 (mean difference in probability of death -1.1%). However, mortality probabilities above age 60 are lower using our estimations than either WHO or UNPD. The mean difference between our sample and the WHO is 5.9% (95% CI 3.8-7.9%) and between our sample is UNPD is 13.5% (95% CI 11.6-15.5%). Regardless of the comparator, the difference in mortality estimations rises monotonically above age 60.InterpretationMortality estimations above age 60 in ten African countries exhibit large variations depending on the method of estimation. The observed patterns suggest the possibility that survival in some African countries among adults older than age 60 is better than previously thought. Improving the quality and coverage of vital information in developing countries will become increasingly important with future reductions in mortality.
| S-EPMC3197519 | biostudies-literature
Project description:IntroductionLow physical capability predicts mortality, perhaps by association with co-morbidity. However, few studies include participants <70years old with lower co-morbidity burdens compared to older adults. We examined relationships between usual walking speed (UWS), timed chair stands speed, grip strength, standing balance and all-cause mortality in 8477 participants aged 48-92years enrolled in the European Prospective Investigation of Cancer-Norfolk study.MethodsParticipants (55.1% female) were followed up for 6.0 years (inter-quartile range 4.6, 7.5). Associations were examined using Cox proportional hazards regression by age-group (<70years versus ≥70years) and then in the whole cohort adjusted for age, sex, anthropometry, history of diabetes/stroke/myocardial infarction/cancer, smoking, alcohol intake, socioeconomic status, television viewing time and physical activity.ResultsAge and sex adjusted associations were similar in younger and older participants (Pinteraction all >0.05) and those with lower physical capability had higher mortality risk. For example, in those <70years old hazard ratios (95% confidence interval) for mortality in the third, second and lowest sex-specific quartiles of UWS compared to the highest were 1.21 (0.75, 1.96), 2.11 (1.35, 3.28) and 2.91 (1.84, 4.62) and in participants ≥70years old were 1.19 (0.73, 1.95), 2.09 (1.35, 3.24) and 2.64 (1.73, 4.02) respectively. In the whole cohort, strong associations between all physical capability tests and mortality persisted after multivariable adjustment and after excluding participants with co-morbidity.ConclusionsPhysical capability was independently predictive of future mortality risk with similar associations in late mid-life, when co-morbidity burden is lower, as at older age.
| S-EPMC5701965 | biostudies-literature
Project description: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.
| S-EPMC7409555 | biostudies-literature
Project description:BackgroundThe epsilon2, epsilon3, and epsilon4 alleles of the apolipoprotein E gene (APOE) encode three isoforms, apoE2, E3, and E4, respectively. The apoE isoforms circulate in different plasma concentrations, but plasma concentrations of the same isoform also differ between individuals. Whereas the isoforms have been associated with cardiovascular disease, the relation between plasma apoE levels and cardiovascular disease is unknown.Methods and findingsWe assessed APOE genotypes, plasma levels of apoE, cardiovascular risk factors, and mortality in a population-based sample of 546 individuals aged 85 y who participated in the Leiden 85-plus Study and were prospectively followed for specific causes of death for 5 y. Participants in the highest tertile of apoE levels suffered a twofold-increased risk of cardiovascular mortality (hazard ratio compared to lowest tertile, 2.08; 95% confidence interval [CI], 1.30 to 3.33). Among the 324 participants with the epsilon3epsilon3 genotype, the hazard from cardiovascular disease was threefold increased (highest versus lowest tertile 3.01; 95% CI 1.60 to 5.66), with similar estimates for men and women. Other causes of death were not increased significantly. Plasma levels of apoE in epsilon3epsilon3 participants were positively correlated with total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.001) and triglycerides (p < 0.001) and negatively with high-density lipoprotein cholesterol levels (p = 0.010). Adjustment for plasma lipids did not change the hazard ratios, whereas interaction was absent. The risk associated with high levels of apoE, however, was strongest in participants from the lowest tertile of C-reactive protein (CRP) levels and absent in those from the highest tertile (p(interaction) < 0.001). Among participants from the lowest tertile of CRP levels, those with a high apoE levels had a significantly steeper increase in CRP than those with low apoE levels (p = 0.020). Similar cardiovascular mortality risks as in epsilon3epsilon3 participants were found in epsilon2 and epsilon4 carriers.ConclusionsIn old age, high plasma apoE levels precede an increase of circulating CRP and strongly associates with cardiovascular mortality, independent of APOE genotype and plasma lipids.
| S-EPMC1457005 | biostudies-literature
Project description:Little is known about the types and numbers of mutations that may accumulate in normal human cells with age. Such information would require obtaining enough DNA from a single cell to accurately carry out reliable analysis despite extensive amplification; and complete genomic coverage under these circumstances is difficult. We have compared colon crypts, which are putatively clonal and contain ~2000 cells each, to determine how much somatic genetic variation occurs in vivo (without ex vivo cell culturing). Using high-density SNP microarrays, we find that chromosome deletions, duplications, and gene conversions were significantly more frequent in colons from the older individuals. These changes affected lengths ranging from 73 kb to 46 Mb. Although detection requires progeny of a single mutant stem cell to reach niche dominance over neighboring stem cells, none of the deletions appear likely to confer a selective advantage. Mutations can become fixed randomly during stem cell evolution through neutral drift in normal human crypts. The fact that chromosomal changes are detected in individual crypts with increasing age suggests that either such changes accumulate with age or single stem cell dominance increases with age, and the former is more likely. This progressive genome-wide divergence of human somatic cells with age has implications for aging and disease in multicellular organisms.
| S-EPMC5706647 | biostudies-literature
Project description:ObjectiveHow disability manifests itself in an individual is a highly complex process influenced by a wide range of individual and environmental factors. Its complexity makes the search for generalizable characteristics of the disablement process a challenging task. Consequentially, little is known about how the effect on other health outcomes such as life expectancy are modified after the onset of chronic ailments. In this paper we posit an alternative approach to generalize health trajectories of older people with disability and then analyze how socioeconomic conditions affect the longevity within these trajectory groups.MethodsIndividual level information about the first three successive onsets of chronic disability after age 50 is transformed into state-sequences. We extract trajectory groups based on onset time and the time spent in a certain state. Mortality hazards are then estimated with a Gompertz proportional hazards model to compare effects of different socioeconomic measures within the trajectory groups.ResultsThree distinct trajectory groups are identified, the mild (1), the early severe (2), and late severe (3) pathway. Estimates of the mortality analysis suggest that social inequalities in longevity are less pronounced after onset of old-age disability. We found a consistent survival prolonging effect for individuals who engage in daily activities (such as meeting with friends, walking) that ranged between 33.2% and 77.3%. The importance of other variables varies between trajectory groups.DiscussionThis study shows how health trajectories of individuals with disability can be generalized when information on the onset and severity of single conditions is available. Such an approach may help us to better predict health and care expenditures and help families and individuals with their personal care planning. The findings from the subsequent survival analysis suggest a substantial reduction of socioeconomic mortality differences after onset of old-age disability, which appears to be independent of its nature.
| S-EPMC7470411 | biostudies-literature